Inverse relationship between upright plasma renin activity and twenty-four hour blood pressure variability in borderline hypertension

Office, i.e. measured by the physician at rest, and 24 h ambulatory systolic (SBP) and diastolic (DBP) blood pressures, heart rate, supine and upright plasma renin activities, supine and upright aldosterone concentrations and plasma and urine sodium and potassium were measured in 61 young male subjects aged 19-25 years, including 40 normotensive subjects (office DBP less than or equal to 90 mmHg and office SBP less than or equal to 140 mmHg) and 21 borderline hypertensive subjects (non-normal blood pressures with office DBP less than or equal to 95 mmHg and office SBP less than or equal to 160 mmHg). No significant differences were found in the plasma or urine K+ or Na+, upright or supine plasma renin activity or aldosterone concentration between normotensives and borderline hypertensive subjects. No correlation was detected between plasma and urine K+ or Na+, upright and supine aldosterone concentration or supine plasma renin activity and blood pressure. In contrast, significant inverse correlations were observed between upright plasma renin activity and blood pressure. The correlations were approaching statistical significance when upright plasma renin activity was related to office SBP and office DBP (r = -0.22, P = 0.097 and r = -0.25, P = 0.049, respectively), and were more significant when plasma renin activity was related to 24 h mean DBP (r = -0.32, P = 0.013) and to SBP and DBP standard deviations (r = -0.37, P = 0.004 and r = -0.26, P = 0.04, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Diet and weight loss: their effect on norepinephrine renin and aldosterone levels

The effect of low calorie diet on blood pressure, catecholamines, plasma renin activity (PRA) and aldosterone was examined in 22 obese subjects (19 hypertensives and 3 borderline hypertensives). A significant decrease in blood pressure (P less than 0.05) was observed in all patients after 10 days on the diet. Twenty subjects showed a significant decrease in norepinephrine (NE) levels (P less than 0.05) and two patients showed an extreme increase in NE level. On reexamination six months later these two patients presented with high NE levels and predict blood pressure levels despite having lost 15 and 18 kg respectively. The study group showed a significant decrease in mean PRA (P less than 0.05). A correlation was observed between changes in NE levels and PRA (r = 0.42, P less than 0.05) and between changes in PRA and aldosterone (r = 0.54, P less than 0.05). The reduction in blood pressure associated with caloric restriction in these obese patients may be a result of reduced sympathetic nervous system activity.     

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.     

Endogenous prostaglandin E2 metabolite levels, renin-angiotensin system and catecholamines versus acute hemodynamic response to captopril in chronic congestive heart failure

Hemodynamic and hormonal responses to captopril were measured in 10 patients with severe chronic heart failure poorly controlled by digitalis and diuretics. After administration of a 25-mg dose, stroke volume (SV) increased from 53 +/- 7 to 63 +/- 9 ml (p less than 0.05), while pulmonary wedge pressure (PWP) decreased from 20 +/- 2 to 14 +/- 2 mm Hg (p less than 0.01). The hemodynamic changes were associated with increases in plasma renin activity (PRA; p less than 0.05) and in plasma levels of a novel bicyclo-prostaglandin E2 metabolite (bicyclo-PGE-m; p less than 0.01), whereas norepinephrine (NE) showed a falling tendency. In general, basal hemodynamic and basal hormonal levels did not correlate. Captopril-induced changes in mean artery pressure (MAP) and mean pulmonary artery pressure (mPAP) were positively correlated to pre-captopril PRA (r = 0.74, p less than 0.01; r = 0.64, p less than 0.05) and to changes in PRA (r = 0.85, p less than 0.01; r = 0.80, p less than 0.01) with a similar trend for angiotensin II (AII); decreases of systemic vascular resistance were more pronounced in patients with higher control NE levels (r = 0.62, p less than 0.05), the reduction of NE levels being highest in patients with higher basal concentrations (p less than 0.001); the captopril-induced decreases of mPAP and PWP were inversely related to basal bicyclo-PGE-m levels (r = 0.60, p less than 0.05; r = 0.61, p less than 0.05), and changes in mPAP were closely related to basal ratios of AII/bicyclo-PGE-m (r = 0.67, p less than 0.01). Thus, captopril exerts its acute beneficial hemodynamic effect by inhibiting the generation of AII, associated with toning down of sympathetic stimulation and increased production of vasodilating prostaglandins, such as PGE2. The relation between AII and PGE2-counteracting substances-might determine the hemodynamic response to captopril in the patients.     

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.     

Effects of clonidine on blood pressure, noradrenaline, cortisol, growth hormone, and prolactin plasma levels in high and low intestinal tone depressed patients

Systolic blood pressure (SBP), diastolic blood pressure (DBP), norepinephrine (NE) plasma levels, cortisol (CRT), growth hormone (GH), and prolactin (PRL) plasma levels were investigated in 26 high intestinal tone (high-IT) and 24 low intestinal tone (low-IT) depressed patients, before and after the intramuscular injection of clonidine (2.5 micrograms/kg). A positive correlation was found between NE, DBP, and Hamilton Depression Rating Scale (HRS) values in low-IT depressed patients, while a negative correlation was found between HRS/IT and NE in high-IT depressed patients. Although clonidine induced significant reduction of SBP in both groups, the drug reduced DBP and NE in the low-IT group, only. CRT mean level was greater in the high-IT than in the low-IT depressed group. However, clonidine was unable to induce changes in CRT, GH, and PRL mean levels in any depressed group. Our results suggest that the clonidine-induced DBP reduction is a reliable index of sympathetic activity in depressed patients and that both parameters (DBP and IT) are useful physiological markers to differentiate two types of depressive syndromes.     

Effects of high sodium diet on dopaminergic mechanism in normal and hypertensive subjects

To investigate the effects of dietary sodium on the peripheral dopaminergic mechanism, changes of unconjugated plasma dopamine(DA) and its related humoral factors were studied in 8 patients with essential hypertension(EH) and 8 age-matched normal controls(N) while they were receiving ordinary meals (Na, 130-180 mEq daily) followed by higher sodium (250-300 mEq daily) diets for a week. Plasma and urinary DA, norepinephrine(NE) and epinephrine(E) were measured by the highly sensitive COMT-mediated radioenzymatic procedure, which permits an accurate estimation of plasma DA as low as 5-6 pg/ml. Under high sodium diets, blood pressure and heart rate were not changed significantly in N and EH subjects. Urinary NE and E tended to decrease, while urinary DA increased significantly in both groups of subjects (p less than 0.05). There was a significant correlation between urinary sodium and DA (r = 0.590, p less than 0.001), but plasma DA failed to correlate significantly to urinary sodium or DA in all subjects. Plasma NE and E tended to decrease in both N and EH subjects, while plasma DA increased significantly (p less than 0.05) in EH from 7.2 +/- 0.8 pg/ml [mean +/- SEM] to 9.3 +/- 1.0 and slightly in N from 9.1 +/- 1.8 to 11.2 +/- 1.3. Plasma renin activity(PRA) and plasma aldosterone(PAC) were invariably decreased in all subjects, while plasma prolactin(PRL) remained unchanged. A significant correlation was observed between plasma DA and NE under ordinary meals (r = 0.733, p less than 0.01), but this correlation disappeared under high sodium diets. Plasma DA showed an inverse correlation to PAC (r = 0.351, p less than 0.05) under both dietary conditions. Upright posture induced a significant rise (p less than 0.05) in NE, E, DA, PRA and PAC with ordinary meals, but the responses of NE and PAC were apparently attenuated with high sodium diets. An intravenous injection of metoclopramide (MCP, 10 mg), a DA receptor antagonist, provoked a slight rise in plasma NE and DA with ordinary meals, of which responses were further enhanced with high sodium diets. MCP induced a definite rise in PAC and PRL in all subjects under both dietary conditions (p less than 0.01), while plasma E and PRA remained unchanged after MCP challenge. The results lend support to the view that unconjugated plasma DA could be a useful marker of peripheral dopaminergic activity, which might be a physiological regulator responsible for the suppression of aldosterone secretion and sympathetic nerve activity observed during high sodium intake.     

Mechanism of suppression of renin secretion by clonidine in the dog

The mechanism by which clonidine suppresses renin secretion was investigated in pentobarbital-anesthetized dogs in which renal perfusion pressure was controlled by means of an aortic clamp. Clonidine (30 microgram/kg, iv) lowered mean arterial pressure (MAP) from 124 +/- 8 to 104 +/- 4 mm Hg (P less than 0.01) and reduced plasma renin activity (PRA) to 32 +/- 4 percent of the control value (P less than 0.01) after 60 minutes. Ganglion blockade with pentolinium (3 mg/kg, im) decreased MAP from 148+/- 7 to 117 +/- 3 mm Hg (P less than 0.01) and reduced PRA to 55 +/- 13 percent of the control value (P less than 0.05) after 45 minutes. Pentolinium converted the hypotension produced by clonidine to hypertension (108 +/- 9 to 146 +/- 10 mm Hg at 60 minutes, P less than 0.05) and abolished the suppression of PRA (105 +/- 14 percent of control at 60 minutes, P less than 0.05). In a further series of experiments, the effects of oxymetazoline, an alpha-adrenergic receptor agonist which is closely related to clonidine but which does not cross the blood brain barrier, were studied. Oxymetazoline (10 microgram/kg, iv) increased MAP from 127 +/- 3 to 154 +/- 2 mm Hg (P less than 0.01) and elevated PRA TO 176 +/- 22 percent of the control value (P less than 0.02) after 30 minutes. A higher dose of oxymetazoline (30 microgram/kg) increased MAP from 129 +/- 10 to 161 +/- 9 mm Hg (P less than 0.05) and increased PRA to 256+/- 37 percent of control (P less than 0.05) after 30 minutes. Taken together, these data support the hypothesis that the inhibition of renin secretion by clonidine results from a centrally mediated decrease in sympathetic neural activity.     

Total and renal sympathetic nervous system activity in alcoholic cirrhosis

Basal sympathetic nervous system activity was assessed in 8 unmedicated patients with alcoholic cirrhosis using a previously developed radiotracer method for measuring total and renal noradrenaline release to, and clearance from, plasma. Compared to the control group total noradrenaline clearance was significantly increased in the patients with advanced alcoholic cirrhosis (Pugh grade C) [1.89 +/- 0.13 vs 1.51 +/- 0.11 l/min, P less than 0.05) indicating that endogenous plasma noradrenaline levels underestimate total sympathetic nervous system activity in these patients. Renal noradrenaline clearance was similar to controls independent of the severity of the liver disease. Both total and renal noradrenaline release were significantly increased in the patients with cirrhosis. The ratio of renal to total noradrenaline release was similar in cirrhotic (26 +/- 7%) and control (23 +/- 5%) groups. Increased arterial plasma adrenaline levels, indicative of adrenal medullary stimulation, were also evident in the patients with cirrhosis and correlated significantly with total noradrenaline spillover (r = 0.732, P less than 0.05). These results strongly suggest that in patients with cirrhosis, rather than a preferential increase in renal sympathetic tone, the increase is part of a pattern of generalized sympathoadrenomedullary activation. Although renal renin secretion was significantly increased in the cirrhotic group no correlation with renal noradrenaline release was seen (r = 0.199), raising the possibility that in cirrhosis renal sympathetic tone is not a major determinant of renal renin secretion. Finally, renal noradrenaline release did not correlate with renal blood or plasma flow but an influence of the sympathetic nervous system on renal function was suggested by the correlation observed between total noradrenaline spillover and impaired salt (r = -0.683, P less than 0.05) and water excretion (r = -0.702, P less than 0.05) demonstrated in the cirrhotic patients.     

The thermic effect of feeding in older men: the importance of the sympathetic nervous system

We have previously published direct evidence that approximately one third of the thermic effect of feeding (TEF) in young healthy men can be accounted for by the meal-induced increment in sympathetic nervous system (SNS) activity. The elderly are known to have abnormal beta-adrenergic mechanisms and blunted responsiveness to sympathetic stimulation. Therefore, we postulated that the elderly might also have a blunted thermic response to a meal. In the present study, we evaluated the TEF in 25 young (age, 29.4 +/- 4.6 years) and 12 older (66.6 +/- 7.0 years), healthy weight-stable, untrained, nonsmoking men on no medications. Energy expenditure (ventilated hood system) and SNS activity (arterialized plasma catecholamine concentrations and norepinephrine [NE] kinetics) were measured before and following ingestion of an 800-kcal high-carbohydrate meal. At baseline, arterialized plasma NE concentration (P = .001) and appearance rate (P = .05) were 40% and 28% higher, respectively, in the elderly. Resting energy expenditure was related to fat-free mass (r = .54, P less than .01), and was 21% lower in the older men (P less than .01). Energy expenditure increased in both groups following the meal, but this TEF was 48% lower in the older men (P less than .001). This reduced TEF observed in the older subjects was associated with only a slight, nonsignificant, blunting of the SNS response to the meal. The TEF was related to the arterialized plasma NE appearance rate in the young, but not the older group. The TEF was unrelated to either glucose or insulin concentrations in either group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sustained antihypertensive actions of a dual angiotensin-converting enzyme neutral endopeptidase inhibitor, sampatrilat, in black hypertensive subjects.

Our objective was to evaluate the safety and antihypertensive efficacy of sampatrilat, a novel dual inhibitor of both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), in subjects poorly responsive to ACE inhibitor monotherapy. The ability of sampatrilat (50 to 100 mg daily) (n = 28) to lower blood pressure was compared with that of the ACE inhibitor lisinopril (10 to 20 mg daily) (n = 30) using a double-blind, randomized, parallel group study design over a 56-day treatment period in black hypertensives. Changes in systolic (SBP) and diastolic (DBP) blood pressure were determined using repeated ambulatory blood pressure (ABP) monitoring. Both sampatrilat and lisinopril decreased plasma ACE concentrations after 28 and 56 days. The decrease in plasma ACE concentrations (U/L) was greater after lisinopril (-9.33 +/- 0.52) as compared with sampatrilat (-6.31 +/- 0.70) (P = .0001) therapy. Lisinopril, but not sampatrilat, increased plasma renin activity. Lisinopril produced a transient decrease in mean 24-h ABP (mm Hg) at 28 days (SBP = -9.0 +/- 2.3, DBP = -5.7 +/- 1.3; P < .01), which returned to pretreatment values by 56 days of therapy. Alternatively, sampatrilat produced a sustained decrease in mean ABP over the 56-day treatment period (day 28: SBP = -7.3 +/- 1.8, DBP = -5.2 +/- 1.2; P < .01: day 56: SBP = -7.8 +/- 1.5; DBP = -5.2 +/- 0.95; P < 0.01) with a greater treatment effect on DBP than that of lisinopril at day 56 (P = .05). Treatment-emergent adverse events were noted to be similar between both treatment groups. We conclude that the antihypertensive actions of ACE/NEP inhibitor monotherapy in black subjects offers a novel therapeutic approach to patients otherwise resistant to the sustained antihypertensive actions of ACE inhibitor monotherapy.     

Effectiveness of furosemide in uncontrolled hypertension in the elderly: role of renin profiling

BACKGROUND: Despite many advances in the treatment of hypertension, adequate blood pressure (BP) control in elderly patients continues to be a challenge. Optimal control of BP remains elusive because of issues relating to drug dosage and proper choice of therapeutic agents, including questions regarding the role of diuretics. METHODS: We examined the effect of diuretic treatment on BP in 12 elderly hypertensive patients whose hypertension was poorly controlled on previous drug regimens. We also evaluated the relationship of systolic, diastolic, and mean arterial BP (SBP, DBP, MAP, respectively) to changes in plasma renin activity (PRA), serum aldosterone (SA), atrial natriuretic peptide (ANP), and serum chemistries both before and after adding furosemide to the prior antihypertensive agents. RESULTS: At baseline, 83% of patients had low PRA (< 1 ng/mL/h). After furosemide, in 67% of patients, decreases in SBP (166 +/- 5 to 134 +/- 5 mm Hg; P <.001), DBP (82 +/- 4 to 71 +/- 4 mm Hg; P =.004), and MAP (111 +/- 3 to 92 +/- 3 mm Hg; P <.001), were associated with increases in PRA (2.1 +/- 1.2 to 5.1 +/- 1.8 ng/mL/h; P =.01) and SA (4.8 +/- 1.0 to 9.4 +/- 1.4 ng/dL; P =.01) and with decreases in ANP (101 +/- 28 to 58 +/- 11 pg/mL; P =.01) and body weight (77.5 +/- 3.6 to 76.4 +/- 3.3 kg; P =.02), findings consistent with volume mediated/salt sensitive hypertension. In the remaining 33% of patients, BP also decreased significantly, but there was no increase in PRA (0.15 +/- 0.05 to 0.10 +/- 0 ng/mL/h) or SA (9.2 +/- 2.2 to 7.0 +/- 0.8 ng/dL) and no decrease in ANP (66 +/- 5 to 75 +/- 18 pg/mL) (P = ns for all), suggesting alternate mechanisms for their responses. CONCLUSIONS: Many of the elderly hypertensive patients in our study had decreased PRA levels and showed significant reductions in BP after furosemide administration. Despite the associated increases in PRA and SA and decreases in ANP in 67% of patients, diuretic use remains important in the control of hypertension in this population.     

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.     

Changes in plasma norepinephrine after intravertebral artery infusion of saralasin in sodium depleted dogs

This study was designed to investigate the central action of circulating angiotensin II on the regulation of blood pressure in sodium depleted states. The effects of intravertebral arterial infusion of angiotensin II and [Sar-1, Ala-8] angiotensin II (saralasin) on plasma norepinephrine (NE) were studied in alpha-chloralose anesthetized dogs. Intravertebral arterial infusion of angiotensin II (10 ng/kg/min) increased mean arterial pressure (MAP), heart rate (HR) and plasma NE. Plasma NE was decreased by intravertebral arterial infusion of saralasin (0.40 +/- 0.05 to 0.28 +/- 0.04 ng/ml, p less than 0.05) in normal dogs. The administration of furosemide produced significant increases in plasma NE (142.4 +/- 23.7%, p less than 0.01), plasma renin activity (PRA) (158.6 +/- 26.3%, p less than 0.01) and HR (32.3 +/- 6.0 beats/min, p less than 0.01). A slight rise in mean blood pressure (3.9 +/- 1.2 mmHg, p less than 0.05) was observed during the furosemide administration. Saralasin infused into the vertebral artery significantly suppressed the furosemide-induced increases in plasma NE, HR and PRA, and lowered mean arterial blood pressure. Intravenous infusion of the same dose of saralasin produced no changes in arterial blood pressure, HR and plasma NE. These results suggest that the central sympathetic potentiation induced by circulating angiotensin II may contribute to the regulation of blood pressure in sodium and volume depleted states produced by furosemide.     

Reduction of erythrocyte (Na(+)-K+) ATPase activities in non-insulin-dependent diabetic patients with hyperkalemia.

To elucidate the mechanism of hyperkalemia in diabetic patients without renal failure, we investigated (Na(+)-K+) adenosine triphosphatase (ATPase) activity in erythrocyte membrane, erythrocyte Na+ and K+ content, and plasma endogenous digitalis-like substance in control subjects (n = 16) and non-insulin-dependent diabetes mellitus (NIDDM) patients (n = 62). NIDDM patients were divided into normokalemic patients (NKDM, n = 48) and hyperkalemic patients (HKDM, n = 14). There was no difference in plasma glucose or hemoglobin A1c (HbA1c) levels, plasma renin activity (PRA), and plasma aldosterone concentrations (PAC) between NKDM and HKDM patients. (Na(+)-K+)ATPase activities in NIDDM patients were significantly reduced compared with those in control subjects (0.336 +/- 0.016 mumol-inorganic phosphate [Pi]/mg protein/h, mean +/- SEM, P less than .05), and (Na(+)-K+)ATPase activities in HKDM patients (0.243 +/- 0.015 mumol Pi/mg protein/h) were significantly reduced compared with those in NKDM patients (0.295 +/- 0.008 mumol Pi/mg protein/h, P less than .01). Plasma K+ content had a significant negative correlation with (Na(+)-K+)ATPase activity in diabetic patients (r = -.365, P less than .01). Erythrocyte Na+ content had a significant negative correlation with (Na(+)-K+)ATPase activity in control subjects (r = -.619, P less than .05). There was no difference in plasma endogenous digitalis-like substance among the three groups. (Na(+)-K+)ATPase activity was not significantly correlated with plasma endogenous digitalis-like substance in control subjects and diabetic patients. These findings suggest that the reduction of (Na(+)-K+)ATPase activity, which was not related to plasma digitalis-like substance, may be partly responsible for hyperkalemia in diabetic patients.     

Mild essential hypertension in nonobese premenopausal women is characterized by low renin.

The pathophysiological mechanisms in hypertension may differ in men and women. Plasma renin activity was measured in 27 premenopausal, never-treated hypertensive women (blood pressure 141 +/- 2/93 +/- 1 mm Hg) and in 18 age-matched normotensive women (blood pressure 113 +/- 2/71 +/- 2 mm Hg). All subjects were unaware of their blood pressure status. The hypertensive women had on average lower plasma renin activity (0.21 +/- 0.03 nmol/L/h) than their normotensive controls (0.42 +/- 0.07 nmol/L/h, P less than .01). Serum estradiol was also lower in the hypertensive women (0.57 +/- 0.06 v 0.81 +/- 0.09 nmol/L, P less than .05). No difference in epinephrine, norepinephrine, atrial natriuretic peptide, or vasopressin was found between the groups. Plasma renin activity was positively correlated to plasma norepinephrine in the hypertensive women only (r = 0.41, P less than .05). Since low renin hypertension is associated with less cardiovascular complications, this may offer an explanation for the better prognosis of hypertension in women.     

Relationship of plasma renin activity and aldosterone levels with hemodynamic functions in essential hypertension.

Correlates of plasma renin activity and plasma aldosterone levels with hemodynamic functions were studied in 47 male patients with untreated, permanent essential hypertension. All subjects had a normal creatinine clearance and received a diet of 110 mEq/day of sodium. Supine plasma renin activity was directly correlated with cardiac index (P less than.01) and cardiopulmonary blood volume (P=.01).Percentage changes in plasma renin activity and total peripheral resistance in response to upright position were positively correlated (P less than.001). Supine plasma aldosterone level was directly correlated with stroke index (P less than .001) and negatively correlated with hear rate (P less than .05). No significant correlation of aldosterone level was observed with the other measurements, including plasma renin activity. The study points to the neural sympathetic control of plasma renin activity in essential hypertension and suggests the existence of some interrelationships between aldosterone level and cardiac performance.     

不同血压心力衰竭患者肾素-血管紧张素-醛固酮系统的活性

目的为探讨不同血压的充血性心力衰竭(CHF)患者肾素-血管紧张素-醛固酮系统(RAAS)的活性。方法运用放免法测定收缩压(SBP)<100mmHg(1mmHg=0．133kPa)的CHF患者(LPCHF组,22例),SBP>100mmHg的CHF患者(HPCHF组,25例)及健康人(对照组,18例)血浆肾素活性(PRA)、血管紧张素Ⅱ(AngⅡ)及醛固酮(ALD)水平。结果LPCHF组及HPCHF组血浆PRA、AngⅡ和ALD均明显高于对照组(P<0．05～0．01),LPCHF组血清钠、SBP及脉压SBP显著低于对照组(P<0．05～0．01);LPCHF组血浆PRA、AngⅡ和ALD高于HPCHF组(P<0．05～0．01),LPCHF组血清钠、SBP及脉压SBP显著低于HPCHF组(P<0．05～0．01);CHF患者脉压SBP与血浆AngⅡ及ALD呈显著负相关(r=－0．501,P<0．01,r=－0．439,P<0．01)。结论CHF患者体内RAAS活性增高,且SBP<100mmHg者较SBP>100mmHg更高。     

SODIUM, POTASSIUM AND AGE: POSSIBLE DETERMINANTS OF PLASMA RENIN ACTIVITY AND ALDOSTERONE DURING CHILDHOOD (AGE 4–16)

The renin-angiotensin-aldosterone system was studied in fifty healthy children aged 4–16 years under normal sodium and potassium intake. The plasma renin activity (PRA) and plasma aldosterone (PA) decreased with age: r =−0·30, P < 0·05 for plasma renin activity and r =−0·33, P < 0·05 for plasma aldosterone. Significant negative correlation was obtained between plasma renin activity and the 24-h urinary sodium excretion; r =−0·40, P < 0·01. This relationship remained significant when the daily urinary sodium excretion was corrected for 1·73 m² body surface area (BSA); r =−0·40, P < 0·01. Using the multivariance analysis, plotting the plasma renin activity against the two combined parameters (24-h urinary sodium excretion and age), no improvement was obtained (r = 0·38, P > 0·05). This finding suggests that during childhood, sodium rather than age has a major modulatory role on plasma renin activity. With advancing age the plasma aldosterone showed a significant positive correlation coefficient with plasma renin activity (r = 0·29, P < 0·05). Multivariance analysis between plasma aldosterone and the two combined parameters, plasma renin activity and age, significantly improved the correlation coefficient (r = 0·42, P < 0·05) suggesting that both plasma renin activity and age play a dominant modulatory role in the control of plasma aldosterone during childhood. Neither 24-h urinary sodium excretion, nor 24-h urinary potassium excretion, improved the multiple correlation coefficient with plasma aldosterone when added to plasma renin activity and age.     

Increased carbon monoxide production in patients with cirrhosis with and without spontaneous bacterial peritonitis

Carbon monoxide, a product of the heme-oxygenase (HO) pathway, is an important endogenous vasoactive substance. Production of CO has not been assessed in human cirrhosis. The aim of this study was to assess production of CO in patients with cirrhosis with and without spontaneous bacterial peritonitis (SBP). CO concentration in the exhaled air and blood carboxyhemoglobin (COHb) levels, as estimates of total HO activity, were determined in 16 healthy subjects, 32 noninfected cirrhotic patients (20 with ascites), and 19 patients with SBP, all nonsmokers. Noninfected cirrhotic patients had a CO concentration in the exhaled air and COHb levels significantly higher compared with values of healthy subjects (2.3 +/- 0.2 ppm vs. 0.7 +/- 0.1 ppm and 1.0% +/- 0.1% vs. 0.6% +/- 0.1%, respectively; P <.05 for both). Patients with ascites had the highest values. Both CO concentration in the exhaled air and COHb levels were very high in patients with SBP (5.6 +/- 0.6 ppm and 1.9% +/- 0.2%; P <.01 vs. the other 2 groups) and decreased slowly after resolution of the infection, reaching values similar to those of noninfected patients 1 month after SBP. In patients with SBP, there was a significantly direct correlation between CO and plasma renin activity (PRA) (r = 0.71, P <.001). In conclusion, these results support the existence of increased CO production in human cirrhosis, which further increases in the setting of SBP. Increased CO production may participate in the disturbance of circulatory function that occurs during severe bacterial infections in cirrhosis.