Impaired response of atrial natriuretic factor to high salt intake in persons prone to hypertension.
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Atrial Natriuretic Factor↗
Biomedical subjects
C Ferrier
Publications and source records attributed to C Ferrier.
Atrial natriuretic peptide in man.
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Atrial Natriuretic Factor↗
Atrial natriuretic factor in mild to moderate chronic renal failure.
The relationship between kidney function and plasma immunoreactive atrial natriuretic factor (irANF) levels as well as the effects of synthetic human ANF-(99-126) were investigated in 13 patients with mild to moderate chronic renal failure. Under basal conditions, glomerular filtration rate averaged 39 +/- 5 (SEM) ml/min/1.73 m2 and blood pressure (BP) averaged 166/107 +/- 7/2 mm Hg; 12 patients were hypertensive. Plasma irANF levels were significantly increased (98 +/- 16 vs 42 +/- 4 pg/ml in healthy control subjects; p less than 0.001) and correlated (p less than 0.05-0.005) inversely with hematocrit (r = -0.65) and positively with systolic BP (r = 0.75) or fractional sodium excretion (r = 0.75). Human ANF-(99-126) infusion for 45 minutes at 0.034 microgram/kg/min augmented (p less than 0.05-0.01) diuresis and urinary sodium, chloride, calcium, phosphate, and magnesium excretion. During the subsequent 45 minutes of human ANF-(99-126) infusion at a rate of 0.077 microgram/kg/min, diuresis and electrolyte excretion remained elevated (p less than 0.05-0.01). Glomerular filtration rate and effective renal plasma flow were not significantly modified, but filtration fraction rose progressively (p less than 0.01). Human ANF-(99-126) infusion decreased BP (p less than 0.05-0.01), produced hemoconcentration (hematocrit + 7%; p less than 0.01) without negative body fluid balance, and increased (p less than 0.01-0.001) plasma norepinephrine, insulin, and serum free fatty acids; plasma aldosterone and renin activity were unaltered during but rose after cessation of human ANF-(99-126) infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Corticosteroid-induced stimulation of atrial natriuretic peptide in man.
UNLABELLED: Previously, we reported elevated plasma immunoreactive ANP (irANP) levels from the 2nd to the 9th day of administering either prednisone, 50 mg/day, or 9 alpha-fludrocortisone acetate (9 alpha F), 0.6 mg/day, to normal humans. To investigate the course of plasma irANP levels during the first 48 h of corticosteroid administration, 9 healthy men (mean age +/- SEM, 24 +/- 1 years) received in randomised sequence A) a 4-h iv infusion of prednisolone sodium tetrahydrophthalate followed by oral administration of prednisone for 2 days; or B) a 4-h infusion of aldosterone followed by oral administration of 9 alpha F for 2 days. Basal supine plasma irANP levels averaged 32 +/- 5 ng/l in study A and 30 +/- 6 ng/l in study B; they were unchanged or even deceased up to 24 h of glucocorticoid or mineralocorticoid administration, but rose (P less than 0.01) to 56 +/- 9 and 62 +/- 12 ng/l at 48 h, respectively, of the two interventions. During glucocorticoid treatment, blood pressure (BP) and indices of the sodium-fluid volume state were unchanged after 48 h. During 9 alpha F administration, body weight increased (1.1 +/- 0.3%, P less than 0.001), whereas urinary sodium excretion (63 +/- 7%, P less than 0.001), hematocrit (4.1 +/- 1.1%, P less than 0.001), and plasma renin activity (38 +/- 4%, P less than 0.001) decreased. CONCLUSIONS: The increase in circulating irANP at 48 h of administration of either a glucocorticoid or a mineralocorticoid demonstrates a distinct but slow response of the ANP system to these corticosteroids in normal humans.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Serum lipoproteins during treatment with antihypertensive drugs.
Hypertension and certain alterations in serum lipoproteins such as a decrease in high density lipoprotein-cholesterol (HDL-C), an increase in low density lipoprotein-cholesterol (LDL-C) and perhaps also elevated triglycerides (Tg), are complementary coronary risk factors. Moreover, it has become evident that several of the drugs used for standard antihypertensive therapy may also interact with lipoprotein metabolism. The following has been observed after 1 to 12 months of treatment. Various diuretics can significantly increase LDL-C and/or very LDL-C and total C/HDL-C ratio, while HDL-C is often largely unchanged; Tg also are often elevated. LDL-C increased in diuretic-treated men and in chlorthalidone-treated postmenopausal women but not in chlorthalidone-treated premenopausal women. The latter may be protected from this side effect. Drug dosages were usually high in these studies. Indapamide, given at a dose of 2.5 mg/day, seems to exert no relevant effect on the lipoproteins. It is not established whether this difference is related to the nature of the drugs or the doses used. There is little doubt that the dose of chlorthalidone used was greater than that required for a full antihypertensive effect of this drug. Several beta-blockers given as monotherapy induce significant increases in Tg and a tendency for decreases in HDL-C. These changes are most prominent on non-selective beta 1+2-blockers without partial intrinsic sympathomimetic activity (ISA), less pronounced on highly selective beta 1-blockers without ISA, and even more discrete or absent on beta-blockers with distinct ISA. Other sympatholytics such as reserpine, methyldopa, debrisoquine, urapidil, clonidine, labetalol, or postsynaptic alpha-blockers (prazosin, trimazosin, doxazosin etc.) did not affect or, postsynaptic alpha-blockers in particular, sometimes even slightly decreased Tg or LDL-C and very LDL-C values. During combination therapy, diuretic-induced increases in LDL-C were at short term prevented or reversed by the concomitant administration of certain beta-blockers, but not by sympatholytics such as reserpine, methyldopa or clonidine. With combined diuretic-prazosin treatment, a tendency for slightly higher HDL-C was reported. Angiotensin converting enzyme inhibitors (captopril, enalapril) and calcium channel blockers (verapamil, nifedipine, nitrendipine, diltiazem) seem to be largely devoid of undesirable effects on serum lipoproteins. Monotherapy with the potent direct vasodilator carprazidil improved blood pressure and significantly increased HDL-C. Whether and to what extent the observed variations in lipoproteins may persist beyond 1 year of treatment is as yet unclear.(ABSTRACT TRUNCATED AT 400 WORDS)
Antihypertensive Agents↗
[History and physiology of atrial natriuretic peptides in man].
The recent discovery of the atrial natriuretic peptide (ANP) system and its possible physiological role in man are discussed. ANPs are produced in the atria of various species, including man. In normal humans the biologically active alpha-ANP, a peptide consisting of 28 amino acid residues, is released into the circulation through cleavage from a larger prohormone which is stored in specific granules in atrial myocytes. The secretion of alpha-ANP from the heart is activated during atrial distension secondary to volume overload or increased atrial pressures. When injected intravenously, synthetic human alpha-ANP can produce a wide spectrum of hemodynamic, endocrine and renal effects. The ANP system may well play an important role in the homeostasis of (central) blood volume and blood pressure.
Amino Acid Sequence↗
Potassium and norepinephrine- or angiotensin-mediated pressor control in pre-hypertension.
Blood pressure (BP), plasma electrolytes, renin, aldosterone, angiotensin II (AII) or catecholamines, the chronotropic effects of intravenous isoproterenol, norepinephrine (NE) or AII, the pressor responses to NE or AII, and the relationship between plasma AII and aldosterone concentrations were studied before and after 10 days of dietary supplementation with potassium 100 mmol/day, in normotensive members of normotensive (N = 12) or hypertensive (N = 12) families, and 11 patients with borderline essential hypertension. Under control conditions, the pressor responsiveness to NE was significantly enhanced in normotensive with positive family history for hypertension and hypertensive subjects; the other variables were comparable in the groups. After potassium supplementation, plasma potassium, renin, aldosterone or AII, and the relationship between AII and aldosterone levels increased significantly, while body weight, plasma catecholamines, the chronotropic effects of isoproterenol, AII or NE, the pressor effects of AII and plasma clearance of AII or NE were unchanged in all groups. In normotensive members of hypertensive families and patients with hypertension, BP was decreased and the exaggerated pressor responsiveness to NE was normalized; these variables were not modified in normotensive members of normotensive families. These observations are consistent with a potassium-remediable disturbance in NE- but not AII-dependent regulation of BP in the pathogenesis of essential hypertension.
Adult↗
Alpha-1-adrenergic blockade and lipoprotein metabolism in essential hypertension.
The effect of the selective alpha 1-antagonist terazosin on serum lipoproteins and certain blood pressure-regulating factors was assessed in 15 patients with essential hypertension. Terazosin given during 8 weeks reduced arterial pressure (from 153/103 +/- 3/2 (SE) to 143/96 +/- 5/2 mm Hg; P less than 0.02) but did not modify body weight, heart rate, blood volume, plasma renin activity, aldosterone and catecholamine levels, or serum cholesterol, triglycerides, and their lipoprotein fractions. In nine of the patients, blood pressure control was not achieved with terazosin monotherapy and the diuretic methyclothiazide, 2.5 mg, was added. After 8 weeks of combined treatment, blood pressure decreased further (P less than 0.05); serum lipids and lipoprotein fractions did not change as compared with placebo or terazosin conditions. These findings indicate that terazosin in monotherapy does not unfavorably influence lipid metabolism.
Adrenergic alpha-Antagonists↗
Blood pressure control in normotensive members of hypertensive families.
The cardiovascular pressor responses to a stepwise increase in plasma norepinephrine or angiotensin II concentrations, induced by infusions, were studied in 23 normotensive subjects with a negative and 25 with a positive family history of essential hypertension. The two study groups had a similar mean age (24 +/- 2 (SD) yr), body weight, blood pressure (112/64 +/- 10/7 mmHg), heart rate, plasma and urinary sodium and potassium, and plasma norepinephrine, epinephrine, angiotensin II, renin and aldosterone levels. However, subjects with positive history differed from those with negative history of hypertension by a decreased pressor dose of infused norepinephrine (89 +/- 29 vs. 135 +/- 66 ng/kg/min; P less than 0.005), and a significant (P less than 0.01) shift to the left of the relationship between norepinephrine-induced changes in mean arterial pressure and concomitant changes in plasma norepinephrine. In contrast, the relation between stepwise increasing plasma angiotensin II levels and induced changes in diastolic blood pressure or plasma aldosterone did not differ significantly between the two study groups. These findings delineate a distinct abnormality which may often occur in normotensive offspring of hypertensive families. It is characterized by a selectively disturbed noradrenergic blood pressure control in the presence of a normal angiotensin-mediated blood pressure and aldosterone regulation.
Adult↗
Adrenergic activity and aldosterone regulation: no evidence for an alpha-1 adrenoceptor-mediated influence in normal subjects.
In normal man the sympathetic nervous system could exert an inhibitory influence on aldosterone responsiveness to angiotensin II. The possible role of alpha-1 adrenoceptors in the modulation of aldosterone response was assessed by studying the changes of plasma aldosterone during infusion of angiotensin II at the doses of 1, 2, 5 and 10 ng/kg.min or after corticotrophin injection, 0.25 mg, in 9 normal subjects before and after treatment with the selective alpha-1 adrenoceptor antagonist, prazosin. Prazosin, given during 3 weeks, did not modify supine arterial pressure, heart rate and the plasma levels of angiotensin II, renin, aldosterone or adrenaline but caused a significant (P less than 0.05) increase of plasma noradrenaline. The correlation relating plasma aldosterone to plasma angiotensin II levels before and during angiotensin II infusion and the response of plasma aldosterone to corticotrophin was not modified by prazosin. These findings suggest that in normal man there is no inhibitory influence of the noradrenergic system on aldosterone responsiveness to angiotensin II mediated by an alpha-1 dependent mechanism.
Adrenocorticotropic Hormone↗
Alpha 1-adrenergic blockade and cardiovascular pressor responses in essential hypertension.
The effects of selective alpha 1-adrenergic blockade with terazosin on blood pressure and cardiovascular pressor responsiveness were assessed in 17 subjects with mild to moderate essential hypertension (mean age, 48 +/- 2 [SEM] years). As compared with a 2-week placebo period, 8 weeks of terazosin treatment (mean dose, 10.5 +/- 1.7 mg/day) caused a fall of supine (from 153/103 +/- 3/2 to 143/96 +/- 4/2 mm Hg; p less than 0.025) and upright (from 145/106 +/- 4/2 to 131/94 +/- 5/3 mm Hg; p less than 0.01) arterial pressure; a marked blunting of cardiovascular pressor responsiveness to norepinephrine, as judged from the pressor dose (from 73 +/- 9 to 2156 +/- 496 ng/kg/min; p less than 0.02) and from the rightward shift (p less than 0.01) of the plasma concentration-blood pressure response curve; and a slight increase in plasma norepinephrine concentration (from 37.7 +/- 3.3 to 52.2 +/- 7.8 ng/dl; p less than 0.01). Heart rate, body weight, exchangeable sodium, blood volume, and norepinephrine plasma clearance; plasma epinephrine, renin, angiotensin II, and aldosterone levels; the relationships between angiotensin II-induced increases in arterial pressure or plasma aldosterone and the concomitant increments of plasma angiotensin II; and heart rate responsiveness to isoproterenol did not change significantly after terazosin treatment. These findings suggest that the fall of arterial pressure induced by selective alpha 1-adrenergic blockade in subjects with essential hypertension is associated with, and probably explained by, inhibition of alpha 1-mediated, noradrenergic-dependent vasoconstriction. alpha 1-Adrenergic receptor antagonism did not modify body sodium concentration, the adrenomedullary component of the sympathetic nervous system, angiotensin II levels, or beta-adrenergic dependent mechanisms.
Adrenergic alpha-Antagonists↗
Alfentanil pharmacokinetics in patients with cirrhosis.
The pharmacokinetics of alfentanil were studied in 11 patients with alcoholic cirrhosis and 10 control patients during general anesthesia. All patients received 50 micrograms . kg-1 alfentanil as an intravenous bolus injection. Plasma concentrations were measured at intervals up to 10 h, using a specific radioimmunoassay technique. Protein binding was measured by equilibrium dialysis. Patients with cirrhosis had a significantly lower (P less than 0.01) plasma clearance of alfentanil of 1.6 +/- 1.0 ml . min-1 . kg-1 (mean +/- SD) instead of 3.1 +/- 1.6 ml . min-1 . kg-1 in the controls. The total apparent volume of distribution was similar in the two groups. The elimination half-life was prolonged from 90 +/- 18 min in the controls to 219 +/- 128 min in the cirrhotics (P less than 0.01). Patients with cirrhosis had a higher (P less than 0.01) alfentanil plasma-free fraction (18.6 +/- 9.4%) compared with the control patients (11.5 +/- 3.9%). When kinetic parameters were corrected for protein binding, the unbound volume of distribution and the free drug clearance were decreased significantly in patients with cirrhosis. Since the concentration alpha 1-glycoprotein to which alfentanil mainly is bound in plasma did not differ in the two groups, it is suggested that the increase in the free fraction is caused by an alteration of binding sites of this protein in patients with cirrhosis. Owing to its delayed elimination and increased free fraction, alfentanil will exert a prolonged and pronounced effect in patients with cirrhosis.
Adult↗
Cardiovascular effects of short-term selective alpha 1-adrenergic blockade with terazosin in patients with essential hypertension.
The effects of selective alpha 1-adrenergic blockade with the agent terazosin on blood pressure and cardiovascular pressor responsiveness as related to major pressor factors were assessed in 17 patients with mild to moderate essential hypertension (mean age +/- s.e.m. 48 +/- 2 years). As compared with a 2-week placebo period, terazosin, given during 8 weeks at a maximal daily dose of 10.5 +/- 1.7 mg, caused a fall of supine arterial pressure (from 153/103 +/- 3/2 to 143/96 +/- 4/2 mmHg; P < 0.05), and a marked blunting of cardiovascular pressor responsiveness to norepinephrine (NE) as judged from the pressor dose (from 0.43 +/- 0.05 to 12.74 +/- 2.93 mmol/kg per min, P < 0.05) and from the shift to the right (P < 0.01) of the correlation relating NE-induced increments of arterial pressure to the corresponding increases of plasma NE during NE infusion. Heart rate, body weight, exchangeable sodium, blood volume, NE plasma clearance, plasma epinephrine, renin, angiotensin (ANG) II and aldosterone levels, the relationships between the ANG II-induced increases in arterial pressure or plasma aldosterone and the concomitant increments of plasma ANG II during ANG II infusion as well as the heart rate responsiveness to isoproterenol did not change significantly after terazosin. The findings of the present study suggest that the fall of arterial pressure induced by selective alpha 1-adrenergic blockade in patients with essential hypertension is associated and probably explained by inhibition of alpha 1-mediated, noradrenergic-dependent vasoconstriction.
Adrenergic alpha-Antagonists↗
[Hemodynamic effects of fentanyl during anesthesia with 2 concentrations of enflurane].
The cardiovascular effects of intravenous fentanyl were determined in eleven patients undergoing intra-abdominal surgical procedures under enflurane anaesthesia. The patients were curarized with pancuronium and ventilated with nitrous oxide (50%) in oxygen. The systemic arterial pressure (Pa) was measured by means of a left radial arterial catheter. The pulmonary artery pressure (Ppa), the pulmonary wedge pressure (Ppw), the cardiac output, the pH and blood gases of mixed venous blood were measured by means of a thermodilution Swan-Ganz catheter. Before the surgical procedure, the measurements were carried out 10 and 20 min after the administration of 0.8% enflurane, and 5 and 15 min after 5 micrograms X kg-1 intravenous fentanyl. During surgery, the measurements were repeated under 0.8% enflurane, and then after 10 and 20 min of receiving 1.6% enflurane, and 5 and 15 min after a second intravenous injection of fentanyl (5 micrograms X kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Thiopentone pharmacokinetics in patients with chronic alcoholism.
The pharmacokinetics of thiopentone were compared in nine control patients and 10 patients with chronic alcoholism (without signs of cirrhosis or hepatitis) undergoing orthopaedic or abdominal surgery under general anaesthesia. The mean (+/- SD) alcohol intake was 92 +/- 14 litre of ethanol per year in the alcoholic patients and less than 10 litre yr-1 in the controls. Thiopentone plasma concentrations were measured by high pressure liquid chromatography after the administration of a single bolus dose (5-9 mg kg-1). The plasma clearance of thiopentone was significantly increased from 3.7 +/- 0.9 ml min-1 kg-1 in the controls to 5.4 +/- 2.2 ml min-1 kg-1 in the patients with chronic alcoholism. The volume of the central compartment and the total apparent volume of distribution were similar in both groups. The terminal elimination half-life was of 684 +/- 168 min in the alcoholics and did not differ significantly from the value found in the controls (750 +/- 212 min).
Adult↗
Disturbed noradrenergic blood pressure control in normotensive members of hypertensive families.
The possible influence of a family history of hypertension on some variables of adrenergic blood pressure regulation was assessed. Blood pressure, heart rate, plasma renin activity, adrenaline and noradrenaline concentrations, and plasma or urinary electrolyte estimations did not differ significantly between two groups of normotensive subjects matched for age and sex with and without a family history of hypertension. Compared with subjects without a family history, however, an appreciably decreased pressor dose of infused noradrenaline, a distinct shift to the left in the relation between noradrenaline induced changes in mean arterial pressure and concomitant plasma noradrenaline concentrations, and an enhanced pressor response to given increases in plasma noradrenaline concentrations occurred in the group with a family history. These findings suggest that an imbalance between cardiovascular noradrenaline responsiveness and circulating noradrenaline is a common familial disturbance which could possibly predispose to the development of essential hypertension.
Adult↗
Correction of cardiovascular hypersensitivity to norepinephrine by potassium supplementation in normotensive members of hypertensive families and patients with essential hypertension.
Blood pressure (BP), plasma levels of norepinephrine (NE) and epinephrine, the chronotropic effect of isoproterenol, and the relationship between variations in BP and concomitant plasma NE levels obtained during NE infusion were studied under control conditions and after 10 days of dietary potassium supplementation (100 mmol/day) in 12 normotensive subjects with negative family history (FH) of hypertension (mean BP 111/70 +/- 9/7 mmHg), 11 normotensive subjects with positive FH (112/73 +/- 8/6 mmHg), and 10 subjects with untreated borderline to mild essential hypertension (131/89 +/- 15/9 mmHg). Under control conditions, the increase in circulating NE required to elevate mean BP by 20 mmHg was significantly lower in hypertensive subjects (6.1 +/- 4.0 nmol/l) or normotensive subjects with positive FH (5.0 +/- 2.4 nmol/l) than in normal subjects with negative FH (9.9 +/- 6.4 nmol/l); the other study parameters were similar. After potassium supplementation, plasma and urinary potassium increased and body weight decreased slightly in all groups; basal plasma NE and epinephrine levels and cardiovascular effects of isoproterenol were unchanged. However, in normotensive subjects with positive FH and hypertensive subjects, the increase in plasma NE required to elevate mean BP by 20 mmHg was normalized (to 8.9 +/- 5.9 and 9.9 +/- 6.9 nmol/l, respectively), while BP tended to decrease slightly. These findings indicate that dietary potassium supplementation may favorably modify noradrenergic BP-regulation in hypertension prone individuals.
Adult↗
Different blood pressure responses to diuretic treatment in normotensive subjects with and without a family history of hypertension.
The possibility that the familial background for hypertension may influence the blood pressure response to diuretic treatment was evaluated in 14 normotensive subjects with negative and 14 normotensive subjects with positive family history of hypertension. Under control conditions, blood pressure, heart rate, body weight, urinary sodium and potassium, plasma sodium, potassium, creatinine, norepinephrine, epinephrine, renin and aldosterone levels did not differ between the two study groups. Each subject received chlorthalidone, 100 mg/day, or indapamide, 2.5 mg/day for eight weeks. Compared with control values, blood pressure was decreased during diuretic treatment in subjects with positive (P less than 0.05), but not in those with negative family history for hypertension. Diuretic-induced decreases in plasma potassium (P less than 0.005), increases in plasma renin activity and aldosterone (P less than 0.005), and a tendency towards higher plasma norepinephrine levels were not different between the two study groups. These findings suggest that the familial background of hypertension may, at least in part, determine the blood pressure response to diuretic treatment.
Adult↗