Natriuretic hormones in young hypertensives and in young normotensives with or without a family history of hypertension.

The behavior of plasma atrial natriuretic factor (ANF) and digoxin-like substance (DLS), and the daily urinary excretion of kallikrein (uKK) were evaluated in young hypertensives and in young normotensives with or without a family history of essential hypertension. Each group was also evaluated, separating those with low plasma renin activity from the total sample. The sample group was made up of 75 young males; 31 hypertensives (mean age 22.7 +/- 2.5 years), 28 normotensives with hypertensive heredity (normotensives F+) (mean age 22.2 +/- 1.9 years) and 16 normotensives (mean age 22.0 +/- 2.1 years). An inverse correlation between ANF and PRA was shown in all groups. In hypertensives, ANF was inversely correlated with uKK (r = -0.664, P less than .0001). Plasma ANF (P less than .012) and DLS (P less than .0001) were higher in hypertensives than in normotensives, while uKK excretion was lower (P less than .0001). Plasma levels of DLS were higher in F+ normotensives than in normotensives (P less than .003). Low renin hypertensives showed the lowest uKK excretion (P less than .0001 v normal-high renin hypertensives). Furthermore, low renin hypertensives showed the highest plasma levels of ANF (P less than .0001 v normal high renin hypertensives) and DLS (P less than .012 v normal-high renin hypertensives). Plasma ANF (P less than .0001) was higher, while uKK was lower (P less than .045) in low renin F+ normotensives than in normal-high renin ones. In conclusion, our data indicate that plasma ANF and DLS are elevated since the early phase of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma renin activity and norepinephrine as predictors for antihypertensive effects of nifedipine and captopril

To examine predictors for the efficacy of antihypertensive agents, we investigated the effects of nifedipine and captopril on blood pressure (BP) and humoral factors in patients with essential hypertension. Eleven essential hypertensive patients (mean age: 54) were treated with long acting nifedipine at 20 to 40 mg/day for 8 weeks and 25 essential hypertensives (mean age: 51) were treated with captopril at 37.5 to 75 mg/day. Blood pressure was measured every 2 weeks. Plasma renin activity (PRA), and plasma concentrations of aldosterone, epinephrine and norepinephrine were determined before and at the end of treatment. Both nifedipine and captopril decreased BP (nifedipine: mean BP 119 +/- 3 to 101 +/- 2 mm Hg, captopril: 124 +/- 2 to 100 +/- 2, P less than .01 for each), whereas neither of them affected heart rate. The 8-week treatment of nifedipine showed no significant effect on humoral factors. Captopril increased PRA by 63% (P less than .05) and decreased plasma epinephrine by 42% (P less than .01) and norepinephrine by 35% (P less than .01). The change in mean BP was positively correlated with pretreatment PRA (r = 0.68, P less than .01) in nifedipine-treated patients and inversely with pretreatment norepinephrine (r = -0.53, P less than .01) in captopril treatment. The results suggest that both nifedipine and captopril were effective antihypertensive agents and that the long term treatment of nifedipine is more effective in essential hypertensives with lower PRA, while captopril is more effective in those with higher plasma norepinephrine concentration.     

Neurohumoral mechanisms and left ventricular hypertrophy: effects of hygienic therapy

To determine the effects of hygienic (non-drug) therapy on blood pressure (BP) control and its relationship to sympathetic tone and left ventricular mass (LVM) in primary hypertension, plasma norepinephrine (NE) and renin activity (PRA), LVM, and nutritional and behavioral status were assessed in 76 borderline to mild hypertensives. Pretherapy plasma NE was related to diastolic blood pressure (DBP) and PRA (r = 0.24, P less than .05 and r = 0.37, P less than .01, respectively). Plasma NE of high renin patients (221 +/- 52) (mean +/- SD) was greater than that of normal renin patients (159 +/- 61, ng/l, P less than .01). LVM was related to systolic blood pressure (SBP) (P less than .001), DBP (P less than .01) and urinary sodium (P less than .05), and inversely related to PRA (P less than .01). Septal wall thickness was related to hostility (r = 0.42, P less than .05). After seven weeks of hygienic therapy, DBP was reduced by 6 mmHg (P less than .01). The change in SBP was related to baseline plasma NE (P less than .05) and inversely related to LVM (P less than .05). These results suggest that raised sympathetic tone may be a pathogenic factor in primary hypertension and that hygienic therapy lowers BP more effectively in patients with raised sympathetic tone and low LVM.     

Relationship between basal and sodium-stimulated plasma atrial natriuretic factor, age, sex and blood pressure in normal man

The relationships between plasma atrial natriuretic factor (ANF), blood pressure (BP) and age have not been clearly defined. We measured plasma ANF levels and BP in 128 normal subjects (65 male; 63 female; mean age 48 years, range 20-87 years) on no medication. In subjects of 75 years or less (n = 120) plasma ANF was 5.7 +/- 0.3 pmol/l (mean +/- SEM). Plasma ANF did not differ between sexes (males 5.6 +/- 0.4 pmol/l, females 5.9 +/- 0.4 pmol/l). There was a positive correlation between plasma ANF and age, correlation coefficient (r) = 0.46, systolic BP (r = 0.44), diastolic BP (r = 0.22) and mean BP (r = 0.37) (all P less than 0.01), but after multiple linear regression analysis plasma ANF only related significantly (P less than 0.01) to age and systolic BP once other factors had been excluded. We also measured plasma ANF after erect and supine posture and during a 21IV normal saline infusion given over 4 hrs (n = 24; age range 21-62 years) after an overnight fast. Mean plasma ANF was 5.9 +/- 1.1 pmol/l erect, 7.4 +/- 1.6 pmol/l supine and rose to 10.1 +/- 1.4 pmol/l after saline (both P less than 0.05 vs basal). Response to saline was assessed as the area under the curve of hourly measurements. Neither this nor peak ANF during saline infusion correlated with age. We conclude that basal plasma ANF is influenced by age and systolic BP but plasma ANF response to acute saline stimulation is not.     

Potassium supplementation lowers blood pressure and increases urinary kallikrein in essential hypertensives

In order to eludicate possible mechanism(s) involved in the blood pressure reduction induced by potassium (K) supplementation, we studied the changes of BP and of some of its regulatory systems, including levels of urinary kallikrein (UKal)--an index of renal kallikrein production. Twenty-four untreated essential hypertensives, with a basal BP of 147/96 +/- 13/7 mmHg and normal renal function, received in crossover, double-blind, randomised fashion, 64 mmol KCl or placebo during two periods of 4 weeks each. At the 4th week of potassium supplementation systolic, diastolic and mean BPs decreased by 6.3 +/- 2 (P less than 0.01), 3.0 +/- 2 and 4.1 +/- 2 (P less than 0.05) mmHg respectively for the supine position, and 5.0 +/- 2, 4.0 +/- 2 (P less than 0.05) and 4.0 +/- 1 (P less than 0.05) mmHg for the standing position. Urinary potassium (K) increased from 55 +/- 4 to 123 +/- 6 mmol/24 hours (P less than 0.001) and UKal from 692 +/- 69 to 1052 +/- 141 mU/24 hours (P less than 0.01). Serum K rose from 3.8 +/- 0.1 mEq/l to 4.1 +/- 0.1 mmol/l (P less than 0.001) and PRA from 0.77 +/- 0.12 to 0.99 +/- 0.14 ng/ml/h (P less than 0.05). Correlations were observed between UKal and urinary K (r = 0.44, P less than 0.0001); between differences in UKal and urinary K and in UKal and urinary Na (r = 0.50, P less than 0.0005 and r = 0.48, P less than 0.001 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Central haemodynamics, baroreceptor sensitivity and alpha 1-adrenoceptor-mediated vascular reactivity during weight-stable sodium restriction in obese men with hypertension

Ten obese men (20-40% overweight) with previously untreated arterial hypertension (WHO stages I and II) were examined before and during sodium-restricted isocaloric diets. The mean (+/- s.d.) daily sodium excretion was reduced from 199 +/- 65 to +/- 25 mmol/24 h. Intra-arterial blood pressure (BP), cardiac output (CO), plasma volume, circulating and urinary noradrenaline (NA), plasma renin activity (PRA) and urinary aldosterone were measured. Vascular reactivity was assessed with intravenous bolus injections of 50, 100 and 200 micrograms phenylephrine, and baroreflex sensitivity was assessed with the R-R interval response to pressure elevations on electrocardiogram. Significant reductions in systolic BP from 163 +/- 18 to 147 +/- 17 mmHg and in diastolic BP from 97 +/- 7 to 88 +/- 9 mmHg occurred during salt restriction. Blood pressure reductions were correlated with changes of urinary sodium excretion (r = 0.71; P less than 0.05). No significant changes in CO, heart rate (HR) or stroke volume (SV) were observed; therefore, BP reduction was secondary to the fall in total peripheral resistance (TPR) from 21.8 +/- 4.1 to 19.0 +/- 4.1 units (P = 0.05). Plasma volume, as well as total blood volume, was not affected by the moderate sodium restriction, but PRA rose from 0.71 +/- 0.1 to 0.87 +/- 0.1 micrograms angiotensin 1/ml per h (P less than 0.05). Urinary aldosterone was increased from 32 +/- 12 to 54 +/- 9 nmol/24 h. No change in venous or arterial concentrations of NA or of urinary NA was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

ANF receptors at the glomerular level in reno-vascular hypertension in rats

The effect that hypertension may have on plasma, atrial ANF levels and on isolate rat renal glomeruli ANF receptors was investigated. Different models of renal hypertension were studied: 1-K, 1-C (BP = 177 +/- 7 mmHg), 2-K, 1-C (BP = 158 +/- 3 mmHg) and their respective controls (BP = 100 +/- 2 mmHg). At this stage of hypertension (two weeks) plasma ANF was 56 +/- 9 and 25 +/- 2 pg/ml in 2-K, 1-C and controls respectively and 124 +/- 22 vs 35 +/- 4 pg/ml in 1-K, 1-C and controls. Atrial ANF content was lower in hypertensive animals. A marked up-regulation of the glomerular ANF receptor density was observed in 2-K, 1-C animals. In the right kidney we found 840 fmol/mg protein and 540 fmol/mg protein, and in the left 1,070 fmol/mg protein against 608 fmol/mg protein in 2-K, 1-C and control animals respectively. No change was observed in glomerular ANF receptor density in 1-K, 1-C animals. We have then demonstrated that glomerular ANF receptor density is higher in 2-K, 1-C hypertensive than in normotensive animals. It could be possible, however, that the receptor density may change during the evolution of high blood pressure in the models of experimental hypertension currently studied.     

Correlates of plasma atrial natriuretic factor in health and hypertension

Plasma concentrations of atrial natriuretic factor (ANF) were compared in normotensive subjects and subjects with untreated, uncomplicated essential hypertension (n = 21 pairs) matched for age, sex, and race. Plasma peptide values were slightly greater (45 +/- 3 vs 36 +/- 3 pg/ml; p less than 0.05) in the hypertensive group. On univariate analysis, age (r = 0.52, n = 47, p less than 0.001) and creatinine clearance (r = -0.30, n = 47, p less than 0.05) were significantly related to plasma ANF concentrations, but arterial pressure was not (r = 0.14, n = 47), in an extended group of normal subjects. In contrast, plasma ANF values were related to arterial pressure in both an extended group of subjects with untreated essential hypertension (r = 0.54, n = 38, p less than 0.001) and in our total heterogeneous pool of hypertensive patients (r = 0.46, n = 79, p less than 0.001), but weak positive associations with age and inverse relationships with creatinine clearance were not statistically significant in either hypertensive group. Similar weak inverse relationships between plasma ANF values and renin-angiotensin-aldosterone system activity were found in both normal and hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of amlodipine on urinary sodium excretion, renin-angiotensin-aldosterone system, atrial natriuretic peptide and blood pressure in essential hypertension.

We studied the effect of amlodipine, a long-acting dihydropyridine calcium antagonist, on blood pressure, urinary sodium excretion, plasma renin activity, aldosterone and atrial natriuretic peptide in six patients (aged 47-63 yrs) with essential hypertension. Patients were placed on a fixed sodium intake of 150 mmol/day. After a control period, amlodipine 10 mg/day was given for two weeks. There was a gradual reduction in supine BP over the first two days of treatment, from 165/103 +/- 5/4 mmHg to 137/92 +/- 6/4 mmHg (P less than 0.001) and BP remained at this level during treatment. Three days after amlodipine was stopped the BP was still reduced at 136/87 +/- 5/4 mmHg but was back to pretreatment levels two weeks later. Plasma amlodipine rose after two weeks of treatment to 29.7 +/- 4.7 ng/ml but had only decreased to 15.0 +/- 3.4 ng/ml three days after the treatment was withdrawn. During the first two days of treatment there was no evidence of an increase in urinary sodium excretion and when amlodipine was withdrawn there was no evidence of sodium retention. Plasma renin activity increased from 1.26 +/- 0.30 to 2.99 +/- 0.68 ng/ml/h (P less than 0.001) and plasma atrial natriuretic peptide fell from 19.3 +/- 7.0 to 11.4 +/- 3.8 pg/ml (P less than 0.03) with two weeks of treatment. This study demonstrates that amlodipine is a long-acting calcium antagonist with a slow onset of action and a slow end of action after withdrawal. This makes it difficult to detect alterations in sodium balance when assessed by changes in urinary sodium excretion. However, one explanation for the increase in plasma renin activity and fall in atrial natriuretic peptide is a small reduction in total body sodium.     

Antihypertensive contribution of sodium depletion and the sympathetic axis during chronic angiotensin II converting enzyme inhibition

The known physiological adaptation of cardiovascular sensitivity to variations in angiotensin II (Ang II) levels would predict that the blood pressure (BP)-lowering effect of Ang II inhibition might be at least partly counterbalanced by enhanced Ang II reactivity. Therefore, factors other than Ang II inhibition per se may contribute to the antihypertensive mechanisms of angiotensin converting enzyme (ACE) inhibitors. In order to further investigate this, the body sodium-blood volume state as well as the pressor reactivity to infused Ang II or norepinephrine (NE) were assessed in 12 normal subjects and 16 patients with essential hypertension given a placebo, and after 6 weeks of intervention with enalapril (20-40 mg/day). Enalapril produced in both groups similar falls in plasma ACE activity (P less than 0.0001) and upright plasma aldosterone (P less than 0.01), and a rise in plasma renin activity (PRA; P less than 0.05). BP decreased from 156/107 +/- 3/2 (mean +/- s.e.m.) to 142/94 +/- 5/3 mmHg (P less than 0.001) in the hypertensives and from 118/84 +/- 4/2 to 111/73 +/- 4/3 mmHg (P less than 0.01) in the normal subjects. In the hypertensive patients only, the Ang II pressor reactivity relative to Ang II plasma levels during Ang II infusion was increased (P less than 0.01), while the NE pressor reactivity relative to NE plasma levels during NE infusion (P less than 0.01) as well as the exchangeable body sodium (-5%, P less than 0.001) were reduced significantly. Blood and plasma volume, levels of plasma atrial natriuretic factor and catecholamines, and the heart rate and its response to isoproterenol were unchanged in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determination of the atrial natriuretic factor in patients with essential and renovascular hypertension

We have measured the basal circulating level of atrial natriuretic factor (ANF) in hypertensive patients. Plasma ANF concentrations in 101 patients with mild untreated, essential hypertension and in 64 normotensive controls were 14.9 +/- 11.1 vs 11.9 +/- 7.7 pg/ml, p = NS respectively. Plasma ANF levels in the patients were correlated with mean arterial pressure (r = 0.35, p less than 0.001) and age (r = 0.38, p less than 0.001). Sixteen patients with uncontrolled hypertension despite treatment, had significantly higher plasma ANF levels (33.5 +/- 27.3 pg/ml, p less than 0.001). Forty other patients with hypertension were subjected to an abdominal aortography and a renal vein catheterism, in order to rule out renovascular hypertension. Of these subjects, 16 were without significant renal artery stenosis, 12 had left renovascular hypertension and 12 others right renovascular hypertension. Plasma ANF levels were maximal in the aorta and there were no differences between the ANF levels in the renal veins, whether the stenosis was on the right or left side. In conclusion, plasma ANF levels were not elevated in 101 untreated patients with mild essential hypertension. Together with the evidence of elevated intra atrial pressure in mild essential hypertension, as found by others, this suggests that ANF secretion might be impaired in this disease.     

Importance of overweight in studies of left ventricular hypertrophy and diastolic function in mild systemic hypertension

The relations of Metropolitan Life Insurance Co. Relative Weight values and blood pressure (BP) to minimal forearm vascular resistance, ventricular septal and posterior wall thickness, left ventricular (LV) mass index and cardiac diastolic function were assessed in 31 men, 37 +/- 2 (mean +/- standard error of the mean) years of age. Eighteen patients with untreated mild hypertension were compared with 13 normotensive control subjects of similar age and weight. The hypertensives had higher clinic (137 +/- 3/96 +/- 2 vs 121 +/- 4/81 +/- 3 mm Hg, p less than 0.001/less than 0.001) and home (p less than 0.001) BP. Despite higher BP, the hypertensives did not have significantly greater values than normotensives, respectively, for minimal forearm vascular resistance (2.20 +/- 0.12 vs 2.04 +/- 0.11 U), ventricular septal (9.9 +/- 0.5 vs 10.2 +/- 0.3 mm) and posterior wall thickness (10.2 +/- 0.4 vs 10.0 +/- 0.3 mm) or LV mass index (106 +/- 6 vs 107 +/- 6 g/m2). Furthermore, diastolic peak filling rate, an index of LV diastolic function, was virtually identical in the 2 groups (2.71 +/- 0.14 vs 2.69 +/- 0.07 liters/s, difference not significant). Correlates of peak filling rate included relative weight (r = -0.62, p less than 0.001), posterior wall thickness (r = -0.51, p less than 0.01) and age (r = -0.45, p less than 0.05). Relative weight also correlated significantly with posterior wall (r = 0.59, p less than 0.005), ventricular septal (r = 0.47, p less than 0.005) and LV mass index (r = 0.38, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Calcium metabolism and blood pressure in children

Raised urinary calcium excretion has been reported in patients with essential hypertension, but it is not known whether this finding is an early expression of altered calcium metabolism or a consequence of longstanding high blood pressure (BP). BP and 24 h urinary excretion of calcium, sodium and creatinine were measured in a representative sample of healthy normotensive sixth grade school boys (n = 146: mean age 11.2 +/- 0.1 yrs, SEM). A significantly higher calcium output was found in children in the upper quarter of the BP distribution, even when differences due to body size, urinary creatinine and sodium excretion were excluded. The same result was obtained when students from the upper BP quartile were compared with age, height and weight-matched students from the rest of the study population (urinary calcium: 2.63 +/- 0.42 vs 1.54 +/- 0.23 mmol/24 h, P less than 0.02). Enhanced urinary calcium excretion is thus found in children in the upper part of the BP distribution for their age and sex and who are therefore at higher risk of hypertension in adulthood. This finding is compatible with the hypothesis of a primary abnormality of calcium metabolism in essential hypertension.     

Office blood pressure underestimates ambulatory blood pressure in peripheral arterial disease in comparison to healthy controls

Patients with peripheral arterial disease (PAD) constitute a subgroup of high-risk hypertensives, but controlled studies on 24-h blood pressure (BP) and diurnal variation of BP are lacking. This study was performed in order to test the hypothesis that office BP (OBP) may underestimate 24-h BP in PAD patients in comparison to a matched control group. In all, 98 male patients (mean age 68 years) with a history of intermittent claudication and an ankle/brachial index less than 0.9, and 94 controls matched for age but without PAD or ischaemic heart disease performed 24-h recordings of ambulatory BP. A total of 59 patients had a history of hypertension and 69 were on treatment with BP-lowering drugs as compared to 17 and 23 of the control subjects, respectively. Office as well as 24-h systolic BP (SBP) were higher in patients as compared to controls (151 +/- 22 vs 140 +/- 20 mmHg, P < 0.001 and 142 +/- 14 vs 133 +/- 15 mmHg, P < 0.001, respectively), but did not differ with regard to diastolic BP. In an analysis of covariance with the continuous factors age, office SBP and the categorical factor antihypertensive treatment, 24-h SBP was higher in PAD patients compared to controls (P < 0.05). The difference between office and night SBP was lower in PAD patients with antihypertensive treatment compared to controls (P = 0.01). In conclusion, Male patients with PAD had higher systolic but not diastolic BP than age-matched control subjects. In PAD patients, 24-h SBP was higher than expected from OBP compared to controls. Night SBP was higher only in patients with antihypertensive treatment. In PAD patients, especially when on antihypertensive treatment, the severity of hypertension may be underestimated when based on OBP only.     

Role of the renin-angiotensin system in the systemic vasoconstriction of chronic congestive heart failure

In 15 patients with severe chronic left ventricular failure, plasma renin activity (PRA) ranged widely, from 0.2--39 ng/ml/hr. The level of PRA was unrelated to cardiac output (CO) or pulmonary artery wedge pressure (PWP), but was slightly negatively correlated with mean arterial pressure (MAP) (r = -0.45) and systemic vascular resistance (SVR) (r = -0.40). After infusion of the angiotensin converting enzyme inhibitor teprotide (SQ 20,881) PWP fell from 26.3 +/- 1.3 (SEM) to 20.3 +/- 1.4 mm Hg (P less than 0.001), CO rose from 3.94 +/- 0.23 to 4.75 +/- 0.31 l/min (P less than 0.001), MAP fell from 87.5 +/- 3.8 to 77.9 +/- 4.1 mm Hg (P less than 0.001) and SVR from 1619 +/- 148 to 1252 +/- 137 dyne-sec-cm-5 (P less than 0.001). The fall in MAP and in SVR was significantly correlated with control PRA (r = 0.68 and r = 0.58, respectively). When subjects were divided on the basis of control PRA the hemodynamic response to teprotide was greatest in the high renin group. PRA rose after teprotide (8.7 +/- 3.4 to 37.9 +/- 7.7 ng/ml/hr, P less than 0.05) but plasma norepinephrine fell (619.1 +/- 103.6 to 449.7 +/- 75.7, P less than 0.05). The renin-angiotensin system thus appears to have an important role in the elevated SVR in some patients with heart failure. Chronic inhibition of converting enzyme should be explored as a possible therapeutic approach.     

Studies on abnormalities of adrenal steroidogenesis in essential hypertension, primary aldosteronism and renovascular hypertension: responses of plasma steroids to angiotensin III

In the present study, effects of angiotensin on the adrenal steroidogenesis were studied in essential hypertension, primary aldosteronism and renovascular hypertension (RVH). Angiotensin III(A III), an analogue of angiotensin II, was administered to 17 normal volunteers (9 male and 8 female), 44 patients with essential hypertension (EH) (15 with high renin; HREH, 15 with normal renin; NREH and 14 with low renin; LREH), 8 patients with primary aldosteronism (5 with adrenal adenoma; APA and 3 with bilateral adrenocortical hyperplasia; IHA) and 5 patients with renovascular hypertension. In all the patients with hypertension and normal subjects, blood pressure (BP) and plasma concentrations of progesterone (P), corticosterone (B), aldosterone (Aldo), 17 alpha-hydroxyprogesterone(17-OHP) and cortisol(F) were measured before and after intravenous administration of A III (0.1, 0.5, 1.0, 10, 20 and 40 ng/kg/min, for 15 min, respectively). 1) BP rose from 164 +/- 19/88 +/- 8 to 180 +/- 19/112 +/- 10 mmHg [systolic BP(SBP); P less than 0.01, diastolic BP(DBP); P less than 0.01] in HREH, from 162 +/- 12/96 +/- 7 to 186 +/- 11/118 +/- 8 mmHg in NREH(SBP; P less than 0.01, DBP; P less than 0.01), 165 +/- 12/94 +/- 8 to 202 +/- 12/126 +/- 9 mmHg in LREH(SBP; P less than 0.001, P less than 0.001) and 118 +/- 8/72 +/- 7 mmHg to 136 +/- 11/88 +/- 8 mmHg in controls (SBP; P less than 0.01, DBP; P less than 0.01). The elevation in NREH and LREH was greater than that in HREH and controls. The elevations of BP both in APA and IHA were remarkably greater than that in controls and as similar as LREH(APA; 174 +/- 21/103 +/- 12 to 204 +/- 18/136 +/- 8 mmHg, IHA; 176 +/- 10/104 +/- 4 to 206 +/- 17/138 +/- 10 mmHg). The elevation in RVH was similar to that in NREH(173 +/- 9/108 +/- 8 to 194 +/- 13/132 +/- 10 mmHg). 2) Plasma P increased from 25.5 +/- 7.5 to 39.5 +/- 13.8 ng/100 ml(P less than 0.001) in HREH, from 28.0 +/- 7.7 to 45.3 +/- 12.7 ng/100 ml(P less than 0.001) in NREH, from 23.8 +/- 8.2 to 47.2 +/- 19.4 ng/100 ml(P less than 0.001) in LREH and 26.6 +/- 11.0 to 43.4 +/- 14.6 ng/100 ml in controls. The increment in HREH or NREH was similar to that in controls(P less than 0.1, respectively), whereas greater than controls in LREH(P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)     

Dysregulation of atrial natriuretic factor in hypertension-prone man

To evaluate the hypothesis of an atrial natriuretic factor (ANF) deficiency in hypertension-prone humans, we investigated plasma ANF and other variables in 116 white offspring of normotensive parents (ONorm) or essential hypertensive parents (OHyp). Ten ONorm and 10 OHyp, all men matched for age and body habitus, were studied after 4 days of low (70 mmol/day) and high (350 mmol/day) dietary sodium intake. After mild sodium restriction, plasma ANF did not differ between ONorm and OHyp (9.7 +/- 0.7 vs. 9.0 +/- 1.3 fmol/L). On high sodium intake, plasma ANF increased in ONorm, but not in OHyp (to 18.3 +/- 1.7 vs. 11.7 +/- 1.7 fmol/L; P less than 0.001). On the other hand, acute responses of plasma immunoreactive ANF (irANF) to saline loading or a norepinephrine-induced rise in blood pressure did not differ significantly between 8 ONorm and 8 OHyp. Fifty-one additional ONorm and 45 OHyp were evaluated during liberal sodium intake. Groups were further subdivided according to whether 24-h urinary sodium excretion was 91 mmol/m2 or less (modest salt intake) or more than 91 mmol/m2 (high salt intake). Twenty-four-hour urinary sodium was similar in the 26 ONorm and 21 OHyp on a modest salt intake (121 +/- 6 vs. 116 +/- 9 mmol) and in the 25 ONorm and the 24 OHyp on a high salt intake (226 +/- 10 vs. 221 +/- 9 mmol). However, compared with ONorm, plasma irANF in OHyp was slightly lower on modest sodium intake (7.7 +/- 0.7 vs. 5.3 +/- 0.7 fmol/L; P less than 0.05) and markedly reduced on high sodium intake (15.0 +/- 1.3 vs. 8.0 +/- 1.3 fmol/L; P less than 0.001). Moreover, the slope of the relationship between plasma irANF and 24-h urinary sodium was flatter in OHyp than in ONorm (z test = 2.4). We postulate a new endocrine syndrome characterized by a relative plasma ANF deficiency during high sodium intake in some hypertension-prone humans. This functional defect becomes apparent during chronic, rather than acute, stimulation of ANF release. It occurs as a familial disturbance and may potentially predispose to the development of hypertension.     

Atrial natriuretic factor in hypertension: bioactivity at normal plasma levels

To ascertain whether small shifts in plasma atrial natriuretic factor (ANF) exerted biological effects in hypertension, we studied the renal, hemodynamic, and hormonal effects of ANF [human ANF-(99-126)] infused at a dose (0.75 pmol/kg/min for 3 hours) that would induce changes in plasma ANF confined to the normal, resting range, in a group of six young men with uncomplicated, mild essential hypertension. During ANF infusions, the patients excreted 11.8 +/- 2.0 mmol (mean +/- SEM) sodium more than during the time-matched placebo phase natriuresis (p less than 0.001, mean increase of 53% above placebo values). Urinary excretion of cyclic guanosine monophosphate rose to more than double (212%, p less than 0.001) placebo values. Plasma renin activity (0.4 +/- 0.05 vs. 0.9 +/- 0.12 nmol/l/hr, p less than 0.0001) and aldosterone concentrations (102 +/- 4 vs. 184 +/- 47 pmol/l, p less than 0.05) were clearly suppressed during administration of ANF. Plasma norepinephrine also fell significantly below placebo values (268 +/- 17 vs. 439 +/- 35 pg/ml, p less than 0.05). Urine volume, the excretion of electrolytes other than sodium, hematocrit, effective renal plasma flow, glomerular filtration rate, and filtration fraction were unaffected by ANF. Similarly, plasma concentrations of epinephrine, arginine vasopressin, adrenocorticotropic hormone, and cortisol were unchanged. Blood pressure and heart rate were unchanged. Minor perturbations in plasma ANF concentrations exert clear biological effects in patients with mild essential hypertension. These data suggest that such minor shifts in plasma ANF are of physiological relevance in mild hypertension and probably contribute to volume homeostasis in this condition.     

Ambulatory blood pressure reduction after rosiglitazone treatment in patients with type 2 diabetes and hypertension correlates with insulin sensitivity increase

BACKGROUND: Within the metabolic syndrome, insulin resistance and compensatory hyperinsulinemia are associated with blood pressure (BP) elevation through various potential mechanisms. Thiazolidinediones are antihyperglycemic agents that decrease insulin resistance. OBJECTIVE: To determine the effect of the thiazolidinedione rosiglitazone on BP and insulin resistance in patients with type 2 diabetes and hypertension. METHODS: In 20 subjects (nine men and 11 women) with type 2 diabetes but with a poor glycemic control, and with poorly controlled or newly diagnosed hypertension, rosiglitazone 4 mg daily was added-on therapy for 26 weeks. At baseline and at the end of the treatment period patients underwent ambulatory blood pressure monitoring, a hyperinsulinemic euglycemic clamp, and blood tests for glucose, insulin, HbA1c, lipids, and routine laboratory parameters. RESULTS: Insulin sensitivity estimated with the clamp significantly increased (Mbw/I index changed from 33.9 +/- 2.6 to 41.9 +/- 3.2 micromol/min per kg per nmol/l, P < 0.001) and the HOMA-IR index significantly decreased (6.34 +/- 0.39 versus 4.40 +/- 0.33, P < 0.001) during rosiglitazone treatment. Ambulatory BP presented small but significant reductions for the total 24-h period (135.3 +/- 1.8 versus 129.9 +/- 1.7 mmHg, P < 0.001 for systolic BP and 76.0 +/- 1.6 versus 71.9 +/- 1.6 mmHg, P < 0.001 for diastolic BP), daytime and night-time. The changes in systolic and diastolic BP correlated with the change in insulin sensitivity (r = -0.78, P < 0.01 and r = -0.68, P < 0.01, respectively). There were also significant reductions in fasting plasma glucose (9.39 +/- 0.41 versus 7.55 +/- 0.31 mmol/l, P < 0.001), insulin (94.0 +/- 0.41 versus 79.5 +/- 5.6 pmol/l, P < 0.01) and HbA1c (8.15 +/- 0.24 versus 7.24 +/- 0.19%, P < 0.001). CONCLUSIONS: Treatment of type 2 diabetic hypertensive patients with rosiglitazone significantly increased insulin sensitivity and lowered ambulatory BP. These changes were strongly correlated. Thiazolidinediones may thus possess a BP-lowering effect beyond their antihyperglycemic properties.     

Measurement of plasma renin concentration using exogenous human renin substrate in normal subjects: correlation with plasma renin concentration and plasma aldosterone concentration.

Measurement of plasma renin concentration (PRC) was done in normal subjects at rest and under acute stimulation of renin release under unrestricted sodium intake. Concurrent measurements of plasma renin activity (PRA) and plasma aldosterone concentration (PA) were carried out. The mean values of PRC at rest and after stimulation of renin release were 12.8 +/- 1.3 (SEM) and 21.7 +/- 4.4 (SEM) ng AT I/ml/h, respectively. These corresponded to renin contents of 3.4 +/- 0.34 (SEM) X 10(-5) Goldblatt units and 5.8 +/- 0.36 (SEM) respectively. The mean percent increase of PRC (82.1 +/- 19.3 (SEM)) %) was almost indentical to that of PA (81.5 +/- 16.4 (SEM) %), but differed from that of PRA (269 +/- 83.1 (SEM) %). A very high correlation between concurrent PRC and PA (r = 0.92, P less than 0.001) was found in normal subjects at rest and under acute stimulation of renin release. A good correlation between PRC and PRA (r = 0.85, P less than 0.001) was also observed. However, a higher correlation between percent increases of PRC and PA (r = 0.92, P less than 0.001) than that of PRA and PA (r = 0.80, 0.01 less than P less than 0.005) was found. Results show that PRA is a good index of the renin content in plasma in normal subjects at rest and PRC reflects actual renin concentration in plasma at rest as well as under stimulation of renin release.