Plasma levels of atrial natriuretic factor in mild to moderate hypertensives without signs of left ventricular hypertrophy: correlation with the known duration of hypertension

The relationship between plasma atrial natriuretic factor (ANF), blood pressure (BP), age, plasma renin activity (PRA) and urinary sodium excretion was studied in 64 normal subjects (mean age 48.7 +/- 2.1 yrs; BP: 126.5 +/- 1.6/79.5 +/- 0.9 mmHg) and in 104 untreated uncomplicated essential hypertensives (50.8 +/- 1.1 yrs; BP: 164.7 +/- 1.6/105.2 +/- 0.6 mmHg). ANF was measured by radioimmunoassay after extraction on C18 columns. ANF was significantly higher in the hypertensives than in the normal subjects (37.1 +/- 1.2 vs 29.7 +/- 1.5 pg/ml, P less than 0.01). In normals plasma ANF was significantly correlated with age (r = 0.72, P less than 0.001), Na excretion (r = 0.42, P less than 0.001) and PRA (r = -0.71, P less than 0.001) whereas in the hypertensives ANF plasma levels correlated only with systolic (r = 0.46, P less than 0.001) and diastolic (r = 0.51, P less than 0.001) BP. In addition in hypertensive patients, by multivariate linear regression analysis, a significant correlation was found between age, known duration of hypertension and plasma ANF. The partial correlation coefficient between duration of hypertension and plasma ANF was highly significant (r = 0.80, P less than 0.001). These findings suggest that in essential hypertension the level of arterial BP is a main determinant of the ANF plasma values offsetting the ability of other physiological factors to regulate plasma ANF levels.     

Plasma insulin levels do not change during atrial natriuretic factor infusion in human essential hypertensives

In order to evaluate the effects of atrial natriuretic factor (ANF) infusion on plasma insulin (IRI) in hypertension, 32 essential hypertensives (aged 40 to 62 years) were studied. After 1 week of pharmacologic washout under normal sodium intake (120 mEq of Na+/day), patients were randomly assigned to receive either ANF (0.04 micrograms/kg/min) or its vehicle (50 mL of isotonic saline) over a 60-min period in supine position. Plasma IRI and glucose were measured at -60, 0, 20, 40, 60, 120, 180, and 240 min (infusion time: from 0 to 60 min). Plasma levels of IRI and glucose did not change significantly during ANF infusion. On the contrary, after ANF discontinuation plasma IRI rose from levels of 13.5 +/- 6.4 microU/mL at 60 min to values of 20.1 +/- 11.3 microU/mL at 240 min (P less than .0001 v time 0). Plasma glucose showed a similar behavior, increasing from values of 100.4 +/- 5.0 mg/dL at 60 min to values of 120.0 +/- 5.1 mg/dL at 240 min (P less than .02 v time 0). Our findings suggest that ANF did not influence insulin release in hypertensives. The increase of plasma glucose and IRI observed after ANF discontinuation could be due to the relapse of sympathetic activity, suppressed during ANF infusion.     

Plasma atrial natriuretic peptide in young normotensive subjects with a family history of hypertension and in young hypertensive patients

Plasma atrial natriuretic peptide (ANP) behavior was evaluated in 26 untreated essential hypertensives, 21 normotensives, and 20 normotensives with hypertensive heredity under normal sodium intake (120 mEq of Na+/day). All subjects were men, mean age 22.1 +/- 1.9 years. Plasma ANP was evaluated by radioimmunoassay on samples collected in supine position upon waking and again after 1 h of orthostatism. Resulting data showed that ANP in hypertensives (supine = 44.5 +/- 19.4 pg/mL, orthostatism = 24.1 +/- 11.6 pg/mL) was at higher levels than in controls (supine = 38.3 +/- 19.4 pg/mL, orthostatism = 19.9 +/- 10.6 pg/mL) or in normotensives with hypertensive heredity (supine = 42.1 +/- 16.8 pg/mL, orthostatism = 23.2 +/- 10.8 pg/mL). Mean ANP level was higher in the latter group than in the control group (supine = +9%; orthostatism = +14.2%). In conclusion, plasma ANP is raised in young essential hypertensives, resulting in slightly elevated levels in normotensives with hypertensive heredity.     

Atrial natriuretic factor-specific antibody as a tool for physiological studies. Evidence for role of atrial natriuretic factor in aldosterone and renal electrolyte regulation

Numerous studies have shown that administration of atrial natriuretic factor (ANF) increases urinary sodium excretion and urine flow, decreases blood pressure, and inhibits renin and aldosterone release. However, the role of endogenous ANF in the regulation of renal sodium excretion, blood pressure, plasma renin activity, and aldosterone level remains to be elucidated. To examine this issue, endogenous ANF was blocked by administering rat ANF-(99-126) specific antiserum (Ab) to anesthetized rats (n = 7). Control animals received either no injection (time controls, n = 10) or preimmune serum (n = 8). Blockade of endogenous ANF caused a 28 +/- 0.09%, 47 +/- 0.08%, and 51 +/- 0.08% fall in sodium excretion at 15, 30, and 45 minutes after Ab injection (p less than 0.05, p less than 0.01, p less than 0.01, respectively). Urine flow fell 35 +/- 7% at 45 minutes after ANF inhibition (p less than 0.05). Plasma ANF levels were suppressed to undetectable levels. However, there were no changes in blood pressure throughout the experiment nor plasma renin concentration when measured at 45 minutes after Ab injection. Interestingly, plasma aldosterone concentration increased significantly (by approximately 50%, p less than 0.025), in response to Ab. Completeness of blockade was demonstrated by the absence of sodium excretion response to exogenous ANF (500 ng). In either the time control or the preimmune serum group, urinary excretion, blood pressure, plasma ANF, plasma renin concentration, and plasma aldosterone concentration were unchanged throughout the experiment. In contrast to the Ab group, a challenge with exogenous ANF (500 ng) increased sodium excretion by 2.17 mueq/min in the preimmune serum group.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Disparate effects of mental stress on plasma noradrenaline in young normotensive and hypertensive subjects

The response of blood pressure, heart rate and plasma catecholamines to a mental arithmetic and a cold pressor test was studied in 70 patients with mild essential hypertension and in 41 age- and sex-matched normotensives. Each group consisted of three prospectively stratified age classes: 20-29, 30-39 and 40-55 years. During mental arithmetic, hypertensives showed only a higher increment of systolic blood pressure (+17-19%) than normotensives (+12-15%). Plasma noradrenaline in the youngest normotensives (20-29 years) showed a small but significant decrease (-0.20 +/- 0.07 nmol/l) whereas the youngest hypertensives showed a small but significant increase of plasma noradrenaline (+0.14 +/- 0.04 nmol/l). The difference between both groups was highly significant (P less than 0.001). In the two older age classes there was no difference in plasma noradrenaline response between normo- and hypertensives. During the cold pressor test both the cardiovascular and plasma noradrenaline response were of the same magnitude in normo- and hypertensives. These data reinforce the concept that the increased sympathetic reactivity to mental stress in hypertensives may be restricted to the younger age.     

Elevated insulin, norepinephrine, and neuropeptide Y in hypertension

To investigate the relationship between insulin and sympathetic activity, plasma norepinephrine, neuropeptide Y, serum glucose and insulin concentrations were measured in ten age-, weight-, and sex-matched normotensive and untreated hypertensive subjects at fasting and 2 h following ingestion of a 75 g oral glucose dose. Hypertensives had higher fasting serum insulin (27 +/- 6 v 12 +/- 2 microU/mL; P = .02) and plasma norepinephrine (356 +/- 38 v 235 +/- 35 pg/mL; P = .03) concentrations than normotensives. Glucose load increased serum insulin (P less than .001) and plasma norepinephrine concentrations (P = .001) in both groups and hypertensives had still higher postglucose insulin (P = .003) and norepinephrine levels (P = .003) than normotensives. Fasting neuropeptide Y was higher in hypertensives than in normotensives (P = .03) and correlated with age in both groups (r = 0.7; r = 0.77). Postglucose serum insulin correlated positively with plasma norepinephrine (r = 0.75; P = .013) in normotensives, but these parameters correlated negatively in hypertensives (r = -0.7; P = .036). We hypothesize that elevated plasma norepinephrine and neuropeptide Y levels reflect an increased level of sympathetic nervous activity in hypertensives, which in turn may be responsible for the abnormal relationship between plasma NE and insulin levels.     

Relationship between natriuresis and changes in plasma atrial natriuretic factor, renin activity and aldosterone levels in fasting obese subjects

This study was conducted to assess whether changes in atrial natriuretic factor (ANF) secretion could account for the natriuresis of the early phase of fasting. To this end, 8 AM (supine) and 10 AM (standing) plasma ANF concentrations were determined daily and compared with plasma renin activity and aldosterone levels in 8 obese subjects submitted to a 7-day total fast. Depiste constant daily sodium intake (51 mmol), urinary sodium excretion increased from 35 +/- 7 to 109 +/- 8 mmol/day after 4 days of fast (p less than 0.001) and declined thereafter. Urinary ketone excretion progressively increased over the whole period of fasting (p less than 0.001). Interestingly, fasting induced a decrease in plasma ANF concentrations (p less than 0.05). A contrast analysis revealed no significant change in ANF during the initial natriuretic phase of fasting but a decrease at the end of fasting averaging 36% (p less than 0.05) and 18% (p less than 0.05) at 8 and 10 AM respectively. In contrast, plasma aldosterone rose during fasting (p less than 0.05), the difference being significant at the end of fasting (p less than 0.01). Plasma renin activity and cortisol did not change significantly over the fasting period. Postural and/or diurnal changes of ANF, aldosterone, renin and cortisol were preserved during fasting (p less than 0.01). Postural changes of ANF were, however, attenuated at the end of fasting (p less than 0.05). These data indicate that the fasting natriuresis cannot be explained by changes in ANF levels but that the loss of sodium may contribute to a decline of basal ANF levels, with an attenuation of their physiological postural changes, and to a stimulation of the aldosterone secretion.     

BASAL AND SALINE-STIMULATED LEVELS OF PLASMA ATRIAL NATRIURETIC FACTOR IN ACROMEGALY

We have studied plasma ANF before and after a 4-h intravenous infusion of normal saline in eight subjects with active acromegaly and in eight age and sex-matched control subjects. Plasma ANF, serum aldosterone and blood pressure were measured basally and after 2 and 4 h and plasma renin activity basally and after 4 h. Basal plasma ANF was similar in each group (4.4 +/- 1.5 pmol/l (mean +/- SEM) in acromegalic subjects and 5.3 +/- 0.7 pmol/l in controls NS). Plasma ANF did not rise significantly after saline in the acromegalic group (2-h value, 5.9 +/- 0.9; 4-h value, 5.1 +/- 0.9 pmol/l) but did rise significantly in the control group (2-h value, 8.9 +/- 1.9; 4-h value 9.5 +/- 1.3 pmol/l, both values P less than 0.05 vs basal level). The 4-h ANF value was significantly higher in the control group than in the acromegalic group (P less than 0.05). Basal and stimulated serum aldosterone values were similar in the two groups. Plasma renin activity suppressed to a lesser extent in the acromegalic group after 4 h. The facts that basal plasma ANF was not raised in acromegalic subjects and did not respond to saline stimulation demonstrate that an abnormality of ANF control may be an important factor in the aetiology of the expanded sodium status of patients with acromegaly and hence may contribute to the hypertension seen in patients with growth hormone excess.     

PLASMA DOPAMINE-β-HYDROXYLASE ACTIVITY AND BLOOD PRESSURE VARIABILITY IN HYPERTENSIVE MAN

It has been proposed that measurements of plasma dopamine-beta-hydroxylase (DBH) may allow for assessmetn of adrenergic tone and may elucidate a possible neurogenic contribution to essential hypertension. We performed a series of measurements of DBH in fifty-seven normotensive and fifty hypertensive black and white men in order (1) to compare DBH to selected blood pressure patterns and (2) to evalutate the influence of salt intake, posture and race on plasma DBH. Plasma DBH, measured on unrestricted salt intake with subjects supine, was 42 +/- 4 Units/L in white normotensives, greater (P less than 0.05) than black normotensives (26 +/- 6 Units/L). White hypertensives had greater plasma concentrations of DBH than black (35 +/- 3 VS. 24 +/- 5, P less than 0.05). Normotensives did not differ from hypertensives. Dietary salt restriction and upright ambulation increased plasma DBH activity in hypertensives. Although DBH did not correlate directly with blood pressure, high DBH values were associated with lability of blood pressure in hypertensives but not in normotensives. There are two possible explanations for our results: (1) multiple factors influence plasma DBH activity and plasma levels reflect more than adrenergic function, or (2) essential hypertension is a multifactorial disease and excess sympathetic neuronal activity alone is not sufficient to produce sustained hypertension.     

Enhanced plasma soluble CD40 ligand levels in essential hypertensive patients with blunted nocturnal blood pressure decrease

BACKGROUND: Hypertensives with a blunted nocturnal blood pressure (BP) decrease have increased risk of developing atherosclerotic disease. Soluble CD40 ligand (sCD40L) is involved in the pathogenesis of risk factor-related vascular damage. Therefore, we evaluated the relationship between circulating sCD40L levels, circadian BP profile, and early carotid atherosclerosis in essential hypertensives. METHODS: Plasma sCD40L concentrations were assessed in two groups of 25 never-treated hypertensives, without additional cardiovascular risk factors, differentiated on the basis of a nocturnal decrease of BP either of >10% (dippers) or <10% (nondippers) of daytime values, and in 25 matched normotensives. Carotid intima-media thickness (IMT) was also measured in all participants. RESULTS: Plasma sCD40L concentrations were higher in nondippers (4.9 +/- 1.2 ng/mL) than in dippers (3.7 +/- 0.7, P = .0005) and controls (1.6 +/- 0.6, P < .0001). These latter had lower sCD40L concentrations than dippers (P < .0001). The IMT was higher in both hypertensive groups than in normotensives (P < .0001). In the entire hypertensive population IMT directly correlated with circulating levels of sCD40L (r = 0.365, P = .01) and inversely correlated with nocturnal systolic BP decreases (r = -0.286, P = .043). In a multivariate regression analysis sCD40L was the main determinant of IMT (r(2) = 0.157, P = .004). CONCLUSIONS: Nondippers have enhanced plasma sCD40L levels, which may contribute to their increased susceptibility to develop vascular damage.     

Effects of dietary calcium on atrial natriuretic factor release from isolated rat atria.

Previous studies have shown that acute calcium load causes an increase in circulating plasma atrial natriuretic factor (ANF) levels. The present study was conducted to examine the effect of high dietary calcium on ANF release. Experiments were performed on two groups of male Wistar rats. Hypercalcemic (n = 12) and normocalcemic (n = 12) animals were placed on a high and normal calcium diet, respectively, for 14 days before study. A 24-hour renal clearance was conducted on all animals before superfusion studies. Clearance results showed that high dietary calcium induced a significant increase in plasma calcium (2.69 +/- 0.02 v 2.90 +/- 0.77 mmol/L; P less than .01). This elevation is plasma calcium was associated with a marked increase in calcium excretion (fractional excretion of calcium, 1.91% +/- 0.33% v 8.17% +/- 0.11%, and was correlated with a significant increase in plasma ANF levels (97 +/- 6 v 167 +/- 20 pg/mL). We also measured immunoreactive ANF in the atria of hypercalcemic and normocalcemic rats. ANF content and concentration in the atria were lower in hypercalcemic (465 +/- 36 ng/mg) than in normocalcemic rats (635 +/- 30 ng/mg). This implies that ANF secretion is stimulated by hypercalcemia. To examine this directly, the right atrium from hypercalcemic and normocalcemic rats was superfused in a modified Langendorff preparation. Spontaneous release of ANF from the isolated right atria of hypercalcemic animals (19 +/- 0.8 pg/min/mg) was significantly higher (P less than .01) than from the normocalcemic rats (8.6 +/- 0.3 pg/min/mg). These results suggest that elevation of plasma ANF levels in hypercalcemia is due to an increase in ANF secretion.     

Cytosolic free calcium concentration in platelets in patients with renovascular hypertension and primary aldosteronism.

To investigate the role of cytosolic free calcium, [Ca2+]i, in secondary hypertension, the levels in platelets from 14 secondary hypertensives (7 renovascular hypertension, 7 primary aldosteronism) were compared with those from 21 essential hypertensives and 15 normotensives by means of the fluorescent indicator, quin-2. The mean BP was significantly higher in both the secondary hypertensives and essential hypertensives (122 +/- 8 and 124 +/- 12 mmHg) than in the normotensives (89 +/- 10 mmHg). Cytosolic free calcium in platelets was significantly higher in the essential hypertensives, but not in the secondary hypertensives, compared with the normotensives (182 +/- 34, 141 +/- 17, 138 +/- 15 nM respectively). There was no significant difference in platelet [Ca2+]i between renovascular hypertension and aldosteronism (142 +/- 19 versus 139 +/- 16 nM). There was no correlation between platelet [Ca2+]i and plasma renin activity, plasma aldosterone concentration or plasma noradrenaline concentration in the three groups. Thus, the increase in platelet [Ca2+]i seen in essential hypertension was not found in patients with secondary hypertension. Our results suggest that the cytosolic calcium handling of secondary hypertensive patients with renal artery stenosis or primary aldosteronism differs from that of essential hypertensives.     

Urinary free 18-hydroxy-11-desoxycorticosterone excretion in normal and hypertensive patients.

One hundred fourteen hypertensives and 20 normal controls were examined using a new clinical technique of measuring 24-h urinary free 18-hydroxy-11-desoxycorticosterone (18-OH-DOC) excretion in response to dietary salt manipulations and ACTH injections. The object was to avoid potential errors of random plasma sampling. Mean urinary free 18-OH-DOC in normals on 110 milliequivalent sodium diet was 1.84 +/- 0.69 microgram (mean +/- SD) and represented about 2% of the daily secretion rate of this steroid. Both in normals and hypertensives, urinary free 18-OH-DOC approximately doubled on low salt (P less than 0.01 for each) and rose about 10 times in response to ACTH injection (P less than 0.05 and P less than 0.01, respectively). Plasma and urinary free 18-OH-DOC showed good correlation in patients with essential hypertension on a low salt diet (r = 0.45, P less than 0.01). Suppressed renin patients showed no propensity toward excess 18-OH-DOC excretion and hypertensives with elevated 18-OH-DOC could not be distinguished by their aldosterone levels, cortisol levels, nor their responses to various stimuli. These data suggest 18-OH-DOC is predominantly secreted under ACTH control and, to a smaller extent, in response to salt changes. Hypertension characterized by chronic overproduction of 18-OH-DOC forms only a small percentage of the hypertensive population. It is proposed that measuring 24-h urinary free 18-OH-DOC excretion may be the best method of assessing its rate of secretion without resorting to injection of radiolabeled material.     

Cardiorenal effects of atrial natriuretic factor administration in congestive heart failure: natriuresis and diuresis without hemodynamic alterations

The effects of low bolus dose (70 +/- 6 micrograms [mean +/- SEM]) atrial natriuretic factor (ANF) administration was assessed in 16 patients with chronic congestive heart failure. Measurements were made for at least 60 minutes before and after the dose of ANF. There was a significant increase in urine flow rate (0.81 +/- 0.06 to 1.81 +/- 0.23 ml/min, p less than 0.01), sodium excretion rate (56 +/- 14 to 80 +/- 23 microEq/min, p less than 0.01), fractional excretion of sodium (1.23 +/- 0.49 to 1.63 +/- 0.60 percent, p less than 0.01) and potassium excretion rate (35 +/- 7 to 42 +/- 6 microEq/min, p less than 0.02). However, no significant alterations in renal plasma flow or glomerular filtration rate were observed. Furthermore, there was no significant correlation between the change in urine flow rate or sodium excretion rate and the change in renal plasma flow or glomerular filtration rate, respectively. In addition, there was no significant effect on cardiac index, mean aortic or left ventricular filling pressures, or systemic vascular resistance. There also was no discernible relationship between the response to ANF and the baseline concentrations of plasma ANF, aldosterone, or plasma renin activity. Thus, in patients with congestive heart failure, low dose ANF boluses may produce an increase in urine flow rate and sodium excretion rate that is independent of renal plasma flow or glomerular filtration rate. This suggests a meaningful direct renal tubular effect of exogenous ANF in this setting.     

Effects of posture and ageing on circulating atrial natriuretic peptide levels in man

Possible influences of posture or age on plasma immunoreactive atrial natriuretic peptide (irANP) levels and potential correlates were assessed in 12 young (age +/- s.e.m. 24 +/- 1 year) and 12 elderly (63 +/- 8 year) healthy subjects on a liberal sodium intake. The groups did not differ significantly in their basal 24-h urinary sodium excretion (210 +/- 23 versus 180 +/- 15 mmol/l). However, plasma irANP was five- to ninefold higher in the elderly (P less than 0.05-0.01). Plasma irANP averaged 167 +/- 31 and 24 +/- 3 pg/ml in the elderly and young, respectively, during recumbency, fell (P less than 0.05) to 101 +/- 21 and 11 +/- 1 pg/ml, respectively, with upright posture, and rose (P less than 0.01) to 250 +/- 51 and 50 +/- 9 pg/ml, respectively, after intravenous (i.v.) loading with 0.9% saline (2.14 l in 3 h). Supine blood pressure (BP) and plasma norepinephrine tended to be higher while renin and aldosterone levels were lower (P less than 0.01) in the elderly; the three latter variables rose (P less than 0.001) with upright posture. These findings demonstrate that in normal humans, circulating irANP levels vary with posture and ageing. These changes may have potential physiological relevance and should be considered when interpreting plasma irANP levels in pathological conditions.     

Effects of aging and hypertension on plasma angiotensin II and platelet angiotensin II receptor density.

Plasma renin activity (PRA) declines with age in normal individuals, but the effect of age on plasma angiotensin II (ANG II) is less clear. A decline in plasma ANG II with age could result in altered platelet ANG II receptor density since plasma hormone levels influence their target organ receptors. To investigate this possibility, PRA, plasma ANG II, and platelet ANG II receptor density were examined in 17 young, 12 middle-aged, and 14 elderly healthy normotensive volunteers. To assess whether hypertension altered receptor density, these variables were also examined in 23 hypertensive patients. In normotensives, there was a negative correlation between age and PRA (r = -0.43, P < .05), no significant change in basal plasma ANG II with age, and a weak positive correlation between age and ANG II receptor density (r = 0.34, P < .05). Multiple regression analysis revealed that the relationship between age and ANG II receptor density was independent of the associated rise in mean arterial pressure with age (P < .05). Platelet ANG II receptor density was not significantly related to PRA or plasma ANG II. ANG II receptor affinity did not change with age. Neither PRA nor ANG II receptor density or affinity differed between hypertensives and normotensives of similar mean age, but plasma ANG II was significantly lower in hypertensives compared with normotensives. We concluded that aging is associated with a decline in supine PRA. The small decrease in plasma ANG II was not significant. Platelet ANG II receptor density increased with age primarily due to a small group of elderly subjects with elevated receptor density. There was no change in ANG II receptor density or affinity in hypertensives despite apparently lower plasma ANG II in these patients.     

Reduced activity of the kallikrein-kinin system predominates over renin-angiotensin system overactivity in all conditions of sodium balance in essential hypertensives and family-related hypertension

OBJECTIVE: To study the renin-angiotensin-aldosterone and kallikrein-kinin systems in essential hypertensives and offspring of hypertensive parents during different sodium loads, and to explore their possible influence on renal hemodynamics. METHODS: Forty-five essential hypertensives (35 +/- 4 years old, 25 males), 30 offspring of hypertensive parents (26 +/- 8 years old, 16 males) and 30 normotensive controls (28 +/- 5 years old, 20 males) were submitted to three different sodium loads (high, 250 mmol/l; normal, 140 mmol/l; and low, 20 mmol/l). Blood pressure, plasma renin activity, serum aldosterone, total kallikrein and urinary kallikrein-like activity were measured after each period. Effective renal plasma flow and glomerular filtration rate were also measured. In essential hypertensive subjects, renal hemodynamic and hormonal parameters were also measured after 3 days of 20 mg enalapril administration. RESULTS: Plasma renin activity and serum aldosterone were higher in normotensives, essential hypertensives and offspring of hypertensive parents only during low sodium intake, whereas urinary kallikrein activity was lower in hypertensive offspring and essential hypertensives, compared with normotensives, during the three diet conditions. Effective renal plasma flow was found to be reduced in hypertensives and normotensive offspring, while the glomerular filtration rated was similar in the three groups. Angiotensin converting enzyme inhibitor (ACEI) administration to essential hypertensives for 3 days normalized effective renal plasma flow, increased plasma renin activity and decreased aldosterone and urinary kallikrein activity. CONCLUSIONS: Our observations confirmed the presence of a hormonal imbalance between the renin-angiotensin-aldosterone system and the kallikrein-kinin system, not only in essential hypertensives but also in the offspring of hypertensive parents. This imbalance probably affects the renal circulation and sodium homeostasis, since there was reduced effective renal plasma flow in both populations compared with normotensive subjects. The positive effect of ACEI, resulting in normalization of the effective renal plasma flow in essential hypertensive patients, suggests the involvement of both systems in impaired renal circulation.     

Abnormalities of renal function in essential hypertension with increased circulating levels of insulin-like growth factor I.

An increase in glomerular filtration rate and in tubular Na+ reabsorption from the parenteral administration of insulin-like growth factor I (IGF-I) have been reported in human subjects. To evaluate whether glomerular hyperfiltration and Na+ hyper-reabsorption present in some essential hypertensives are associated to an excess of IGF-I, the plasma levels of this factor and several parameters of renal function were studied in 30 non-treated essential hypertensives and in 30 normotensive controls. IGF-I levels were higher in hypertensive as compared to controls. With the 95% (upper) limit of the normotensive population as a cut-off point, a subgroup of six hypertensives had an abnormally high IGF-I level. Mean blood pressure was slightly lower in these six patients (112 +/- 7 mmHg) than in the remaining patients (120 +/- 2 mmHg). As compared to normotensives and hypertensives with normal IGF-I levels, patients with increased IGF-I levels were characterized by lower (P < 0.01) fractional Na+ excretion and higher (P < 0.05) creatinine clearance. The analysis of the relation of plasma renin activity and the concurrent daily rate of Na+ excretion showed that patients with increased IGF-I were low-renin hypertensives and patients with normal IGF-I were normal-renin hypertensives. These results indicate that an association exists between exaggerated circulating levels of IGF-I and abnormalities of renal function present in some patients with essential hypertension. It is suggested that IGF-I can play a role in low-renin essential hypertension.     

Enhanced antinatriuresis in response to angiotensin II in essential hypertension

Angiotensin II regulates sodium homeostasis by modulating aldosterone secretion, renal vascular response, and tubular sodium reabsorption. We hypothesized that the antinatriuretic response to angiotensin II is enhanced in human essential hypertension. We therefore studied 48 white men with essential hypertension (defined by ambulatory blood pressure measurement) and 72 normotensive white control persons, and measured mean arterial pressure, sodium excretion, renal plasma flow, glomerular filtration rate, and aldosterone secretion in response to angiotensin II infusion (0.5 and 3.0 ng/kg/min). Hypertensive subjects exhibited a greater increase of mean arterial pressure (16.7+/-8.2 mm Hg v 13.4+/-7.1 mm Hg in normotensives, P < .05) and a greater decrease of renal plasma flow (-151.5+/-73.9 mL/ min v -112.6+/-68.0 mL/min in controls, P < .01) when 3.0 ng/kg/min angiotensin II was infused. The increase of glomerular filtration rate and serum aldosterone concentration was similar in both groups. Sodium excretion in response to 3.0 ng/kg/min angiotensin II was diminished in both groups (P < .01). However, the decrease in sodium excretion was more pronounced in hypertensives than in normotensives (-0.18+/-0.2 mmol/min v -0.09+/-0.2 mmol/min, P < .05), even if baseline mean arterial pressure and body mass index were taken into account (P < .05). We conclude that increased sodium retention in response to angiotensin II exists in subjects with essential hypertension, which is unrelated to changes in glomerular filtration rate and aldosterone concentration. Our data suggest a hyperresponsiveness to angiotensin II in essential hypertension that could lead to increased sodium retention.