Muirhead's syndrome--a syndrome of medullipin dependent hypotension.
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Antihypertensive Agents↗
Biomedical subjects
T Hedner
Publications and source records attributed to T Hedner.
Radioimmunoassay of endothelin in human plasma.
A specific and sensitive radioimmunoassay (RIA) for determination of endothelin-1 (ET-1) in human plasma has been developed. Antibodies were raised in rabbits using synthetic ET-1 conjugated to thyroglobulin as immunogen. The antibodies obtained were used at a final dilution of 1:300,000 yielding maximum binding of 61.7 +/- 3.0% (mean +/- 1 SD, n = 20) of 125I-ET-1. The ID50 (inhibitory dose 50%) was 4.5 +/- 0.6 fmol/100 microliters (mean +/- 1 SD, n = 20). The sensitivity of the RIA was 0.33 fmol/100 microliters standard solution. No cross reactivity was observed with endothelin-3, big-endothelin-1, atrial natriuretic factor, angiotensin I or angiotensin II. The cross-reactivity with endothelin-2 was 100%. Endothelin was extracted from acidified plasma with Sep-pak C18 cartridges and recovery of ET-1 added to normal plasma was 70.9 +/- 10.3% (mean +/- 1 SD, n = 12). The concentration of ET-1 in plasma from normal subjects was 1.5 +/- 0.4 pmol/l (mean +/- 1 SD, n = 11) ranging from 1.0 to 2.2 pmol/1. Extracts of normal human plasma subjected to high performance liquid chromatography on a reverse phase C18 column showed one peak of immunoreactivity co-eluting with the standard for ET-1. From these data it is concluded that the immunoreactive material measured in normal plasma with the present RIA is identical to ET-1.
Animals↗
Peptides as targets for antihypertensive drug development.
AIM: To assess the potential for development of new classes of pharmacological drugs in the treatment of hypertension and cardiovascular disease. BACKGROUND: Basis of pharmacological blood pressure reduction: Since the discovery of the renin-angiotensin system by Tigerstedt almost 100 years ago, a large number of vasoactive peptides have been discovered. By interaction with such peptides of endocrine, perivascular or endothelial origin, blood pressure may be modulated. BLOCKADE OF THE RENIN-ANGIOTENSIN SYSTEM: The success of the angiotensin converting enzyme (ACE) inhibitors in hypertension and congestive heart failure is generally attributed to reduced generation of angiotensin II. The recent development of specific and highly potent Ang II type 1 subtype receptor antagonists such as losartan (DuP753, MK954) have provided a new opportunity to inhibit the renin-angiotensin system, and this is currently being explored in hypertensive patients. In addition, blockade of the first and rate-limiting reaction of the renin-angiotensin system, inhibition of renin activity, is also a target for the development of antihypertensive drugs. However, this development is hampered at present by a compensatory increase in active renin that clinically offsets the antihypertensive action of renin inhibitors. PHARMACOLOGICALLY INDUCED INCREASE IN ATRIAL NATRIURETIC PEPTIDE (ANP): The availability of circulating or tissue ANP may be increased by inhibiting its metabolic clearance by NEP-24.11 inhibitor drugs. These agents induce a reduction in blood pressure and diuretic effects in animal models, and may become a new class of drugs for the clinical management of patients with hypertension and congestive heart failure. OTHER POTENTIAL PHARMACOLOGICAL TARGETS IN THE MANAGEMENT OF HYPERTENSION: There are several potential pharmacological targets that may lead to the development of novel antihypertensive agents in the future. These include the interaction or blockade of vasopressor peptides. Routes of development include neuropeptide Y1 receptor antagonists, which block the postjunctional vasopressor effect of neuropeptide Y, or endothelin antagonists, which block endothelin pressor actions at the endothelin A receptor site. The cardiovascular actions of the functional neuropeptide Y inhibitor alpha-trinositol (PP 56) provide a potential new mechanism for reducing blood pressure in hypertension. In addition, the recent discovery of small molecular agents with high potency and specificity for the endothelin A receptor subtype may also be of value in specific vascular disease states. CONCLUSIONS: Future development is likely to provide us with novel drugs based on interactions with vasoactive peptides that may improve the management of specific cardiovascular disease states.
Amino Acid Sequence↗
Enhanced risk of thromboembolic disease in hypertension from platelet hyperfunction and decreased fibrinolytic activity: has antihypertensive therapy any influence?
Enhanced platelet function and a decrease in fibrinolytic activity have been reported in patients with mild hypertension after treatment with various nonselective beta-blockers. Until now, such changes have not been reported during treatment with beta 1-selective drugs or with agents that have intrinsic sympathomimetic activity. The impact of angiotensin-converting enzyme inhibitors and diuretics on platelet function and fibrinolytic activity has not been fully elucidated. Calcium antagonists of various types, however, are known to decrease platelet release in vivo whereas their effects on platelet aggregation and fibrinolytic activity are less clear. The new dihydropyridine calcium antagonist isradipine, when tested in a group of patients with mild hypertension, resulted in a decrease in platelet aggregation, a shortened euglobulin clot-lysis time, and a dramatic increase in t-PA (tissue-plasminogen activator) activity after 14 days of treatment. These changes remained stable throughout the 1-year study period. The fact that antihypertensive therapy does not always result in the hoped-for prolongation of life, despite satisfactory blood pressure reduction, may be in part due to an unfavorable impact on various components of the blood-clotting system.
Antihypertensive Agents↗
Comparative effects of verapamil and volume overload on atrial natriuretic factors and the renin-angiotensin aldosterone-vasopressin system.
The authors compared the effects of verapamil (120 mg three times daily for 3 days) with those of acute volume expansion with normal saline on the plasma levels of atrial natriuretic factors (ANF), renin (PRA), angiotensin II (AII), aldosterone (ALD), and arginine-vasopressin (AVP) in healthy subjects. A randomized, double-blind, placebo-controlled study of crossover design was employed, where each individual received two acute volume overloads 1 week apart, one during placebo and the other during treatment with verapamil. Verapamil reduced blood pressure (BP) and increased the plasma levels of ANF, PRA, AII, ALD, and AVP. Strong positive correlations were observed between PRA, AII, ALD, and AVP, but not with ANF. Acute volume expansion (1500 mL saline in 15 minutes, in supine legs-up position) similarly to verapamil increased ANF levels; however, opposite to verapamil, it reduced PRA-AII-ALD, did not modify AVP levels, and increased BP. The mechanisms of these changes are discussed. In verapamil-treated subjects, volume expansion produced an additional increase in ANF and inhibited the PRA-AII-ALD axis, suggesting that in young healthy individuals, verapamil does not interfere with the reflex compensatory hormonal mechanisms activated under circumstances of acute volume-salt overload, with rapid expansion of the central vascular compartment. Our study indicates that verapamil and volume expansion represent two different stimuli for ANF secretion associated with opposite changes in the PRA-AII-ALD axis. In addition, verapamil can be used as a tool to study and understand the simultaneous increases in ANF and in PRA, AII, and AVP, characteristics of congestive heart failure.
Adult↗
Effects of clonidine on renal sympathetic nerve activity, natriuresis and diuresis in chronic congestive heart failure rats.
The differential effects of the alpha-2 adrenergic agonist, clonidine, on blood pressure, renal sympathetic nerve activity (RSNA) and renal responses were investigated in conscious as well as anesthetized congestive heart failure (CHF) rats and normal control animals. After the stepwise increments of i.v. clonidine infusion (5, 15 and 30 micrograms/hr for 1 hr), mean arterial pressure gradually decreased in CHF, but increased significantly in the control animals at the higher doses. Urinary volume, sodium and potassium excretions were significantly higher in the normal control animals after the clonidine 30-micrograms/hr infusion compared with the CHF rats. There were almost immediate decreases in RSNA in both the CHF and control groups. Although the control animals reduced RSNA to about 5%, the CHF rats retained 36.5% of their respective control values after clonidine administration. Base-line plasma immunoreactive atrial natriuretic peptide were increased 7-fold in the CHF rats compared to controls. After clonidine, immunoreactive atrial natriuretic peptide increased more than 3-fold in the normal rats, whereas no changes were observed in the CHF group. Our data show that clonidine decreases RSNA in CHF and that the natriuretic and that diuretic effects of an alpha-2 receptor agonist are blunted in experimental CHF. Furthermore, the different mean arterial pressure response in the CHF and control groups at higher doses of clonidine may suggest down-regulation of the vascular alpha-2 adrenergic receptor in CHF.
Animals↗
Effects of d-myo-inositol-1,2,6-trisphosphate on neuropeptide Y-induced potentiation of various vasoconstrictor agents in the rat.
The adrenergic cotransmitter neuropeptide Y (NPY) induces vascular smooth muscle contraction by occupying postsynaptic Y1 receptors and by enhancing the vasoconstriction induced by a series of other pressor agents. In particular, NPY modulates the blood pressure response to alpha-1 adrenergic agonists and angiotensin II. The inositol phosphate derivative, d-myo-inositol-1,2,6-trisphosphate (PP56), is a novel NPY antagonist which within a defined dose range selectively blocks the effects of exogenously administered NPY in vivo. In the pithed animal as well as in the freely moving Sprague-Dawley rat, an i.v. bolus administration of PP56 (2 mg/kg) followed by an infusion (20 mg/kg/hr for 30 min) inhibited the approximate 50% increase in mean arterial blood pressure induced by a continuous infusion of NPY (2 micrograms/kg/min for 10 min). Furthermore, PP56 treatment completely inhibited the enhancement induced by NPY (0.1 microgram/min for 50 min or 2 micrograms/kg/min for 10 min) of the pressor responses to preganglionic sympathetic nerve stimulation (in the pithed rat) and to i.v. bolus injections of noradrenaline (20 ng), the indirect sympathomimetic tyramine (40 micrograms) as well as to angiotensin II (10 ng). These results show that PP56, representing a new class of synthetic nonpeptide drugs, is capable of antagonizing the vascular smooth muscle contractile as well as the potentiating effects of NPY in vivo in the pithed as well as the conscious rat.
Angiotensin II↗
[Ambulatory blood pressure measurement--guidelines for registration and data processing].
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Ambulatory Care↗
D-myo-inositol-1,2,6-trisphosphate is a selective antagonist of neuropeptide Y-induced pressor responses in the pithed rat.
The antagonistic effects of a new inositol phosphate derivative, D-myoinositol-1,2,6-trisphosphate (PP56), on pressor responses to preganglionic sympathetic nerve stimulation and exogenously administered phenylephrine or neuropeptide Y (NPY) were investigated in vivo in the pithed rat. In this model an intravenous (i.v.) bolus administration of PP56 (1-50 mg/kg) dose dependently inhibited the increase in mean arterial blood pressure (MAP) induced by a continuous infusion of NPY (2 micrograms/kg per min for 10 min). PP56 in a dose of 5 mg/kg i.v. bolus reduced the entire NPY dose-response curve (0.4-8 microgram/kg per min 10 min infusion) without any shift to the right indicating a non-competitive interaction. Furthermore, PP56 (10-50 mg/kg i.v.) was found to inhibit the pressor response to preganglionic sympathetic nerve stimulation and i.v. bolus injection of the alpha 1-adrenoceptor agonist, phenylephrine. The dose-response curves for increasing doses of phenylephrine and incremental preganglionic sympathetic nerve stimulation were not significantly altered by a lower dose of PP56 (5 mg/kg i.v. bolus). We conclude that PP56, representing a new class of synthetic drugs, can antagonize the actions of exogenous and endogenous NPY in vivo, an action which is specific for NPY within a limited dose range.
Analysis of Variance↗
Antagonistic effects of somatostatin and substance P on respiratory regulation in the rat ventrolateral medulla oblongata.
Substance P (SP) in the dose range 0.75-1.5 nmol exerts a potent stimulatory effect on ventilation after microinjection into the rat ventrolateral medulla oblongata (VLM; n. reticularis lateralis, n. paragigantocellularis lateralis). A significant but less pronounced effect is also seen in the dorsal medulla (DM; n. tractus solitarius). Somatostatin (0.6-1.8 nmol) inhibited ventilation and induced apnoea after microinjection into the VLM but not the DM. Serial microinjections of the two peptides showed a reciprocal antagonistic action in the VLM but not in the DM. The apnoea-inducing effect of SOM was blunted by SP while SOM reduced the ventilatory stimulation induced by SP. Extracellular single unit recordings were performed following the microiontophoretic application of SP and/or SOM to respiratory-related and non-respiratory-related neurons in the VLM and DM. Although a heterogeneous population of neurons were recorded from, the majority of respiratory-related units in the VLM responded with excitation to SP and inhibitory to SOM. A direct interaction between the peptides was seen in some respiratory-related units. The neurons not responding to either of the peptides were usually non-respiratory. Dorsal to the VLM, the type of response to the two peptides was less likely to be antagonistic and a wider distribution of response types were recorded. The results indicate a direct physiological antagonism between SP and SOM regarding their effects on respiratory regulation elicited in the VLM.
Animals↗
Antinociceptive and ventilatory effects of the morphine metabolites: morphine-6-glucuronide and morphine-3-glucuronide.
Morphine and its major metabolites, morphine-3-glucuronide and morphine-6-glucuronide, were given intracerebroventricularly (i.c.v.) to rats. The antinociceptive effects were assessed in the tail-flick and hot-plate tests as well as the writhing test. Ventilatory effects were studied in halothane-anaesthetized rats. Based on calculated ED50 values, morphine-6-glucuronide was approximately 200 times more potent that morphine itself in the tail-flick and hot-plate tests. In the writhing test the difference in ED50 was approximately 9-fold. Morphine and morphine-6-glucuronide administered i.c.v. induced dose-related decreases in minute ventilation in the dose range 2.7 x 10(-9)-1.3 x 10(-7) mol. The dose-response curve for minute ventilation was steeper for morphine-6-glucuronide than for morphine. Morphine-6-glucuronide was approximately 10 times more potent than morphine in depressing minute ventilation. Morphine-6-glucuronide reduced both tidal volume and respiratory frequency, while morphine reduced only the tidal volume. Morphine-3-glucuronide, in contrast, increased both tidal volume and respiratory frequency, causing an increase in minute ventilation. Apnoea was elicited after the highest doses of morphine-6-glucuronide but not of morphine. The potency difference for depression of minute ventilation between morphine-6-glucuronide and morphine corresponded well to the difference in the writhing test but not to the potency difference in the tail-flick or hot-plate tests. The ventilatory depression induced by morphine and morphine-6-glucuronide was readily reversed by naloxone, while the hyperventilation caused by morphine-3-glucuronide was slightly potentiated by the opioid antagonist. Naloxone pretreatment completely blocked the ventilatory depression induced by morphine-6-glucuronide. These results show that the potent ventilatory depression induced by morphine-6-glucuronide is related to its antinociceptive effects in rats. Furthermore, the fact that morphine-3-glucuronide stimulated ventilation and that morphine had a more shallow ventilatory dose-response curve compared to morphine-6-glucuronide may indicate that morphine-3-glucuronide is a functional antagonist of the depressive effects of morphine and morphine-6-glucuronide on ventilation.
Analgesics↗
Haemodynamic, metabolic and endocrine effects of short-term dexfenfluramine treatment in young, obese women.
Seventeen normotensive, premenopausal women were treated with the 5-hydroxytryptamine-reuptake inhibitor dexfenfluramine 30 mg per day, for 4 days in a randomised double-blind, cross-over, placebo controlled trial. Energy intake was held constant during the study as the aim was to study the endocrine and metabolic effects of dexfenfluramine dissociated from its weight-lowering properties. Body weight, blood glucose, plasma insulin, cholesterol triglycerides and C-peptide after an overnight fast and during an oral load of 100 g glucose did not change after dexfenfluramine compared to placebo. Supine and standing systolic and diastolic blood pressures were significantly decreased, while heart rate remained unchanged. Plasma noradrenaline and plasma renin were markedly reduced by dexfenfluramine, and cortisol, beta-endorphin and thyroid hormones were not changed. Thus, dexfenfluramine has a significant hypotensive effect in normotensive, obese women after 4 days of treatment, independent of a negative energy balance. This was associated with decreased circulating plasma noradrenaline, indicating decreased sympathetic nerve activity. Dexfenfluramine may be a candidate drug for longer-term trials in the treatment of primary hypertension associated with obesity.
Adult↗
Effects of diltiazem and metoprolol on blood pressure, adverse symptoms and general well-being. The Swedish Diltiazem-Metoprolol Multi-Centre Study Group.
General well-being, adverse effects and anti-hypertensive efficacy have been investigated in a double blind, parallel-group, dose-response multicentre study of diltiazem and metoprolol monotherapy for hypertension. 128 patients with primary hypertension were included from 10 participating centres. The patients were randomized to receive oral diltiazem 120-240-360 mg/day or metoprolol 50-100-200 mg/day. Each dose was given for a 4-week period as a forced titration regime. In all 119 patients, 59 and 60, respectively, on diltiazem and metoprolol completed the study protocol. There were dose-dependent reductions in supine and standing blood pressures (BP) after both diltiazem and metoprolol therapy. In the diltiazem group, supine BP was reduced by 10 (11)/10 (6) mmHg (SBP/DBP) at the highest dose level, and the corresponding values for the metoprolol group were 7 (16)/8 (9) mmHg (SBP/DBP). Target pressures (DBP less than or equal to 90 mmHg and/or a reduction in DBP of greater than or equal to 10%) were reached in 63% and 48% of the patients, respectively. The incidence and severity of dose-dependent adverse effects, as evaluated by spontaneous reports or open and direct questioning, did not differ between treatments. Subjective well-being, evaluated by a self-administered questionnaire, the MSE-profile, did not differ significantly between diltiazem and metoprolol therapy. However, after an initial slight deterioration, contentment and vitality tended to improve with increasing doses of diltiazem, while a dose-related deterioration in these variables was observed on metoprolol therapy. At the highest dose levels, contentment and vitality tended to be better in the diltiazem than the metoprolol group. Thus, diltiazem and metoprolol in daily doses of 120-360 mg and 50-200 mg, respectively, produce comparable and parallel reductions in supine and standing BP. However, while subjective well-being tended to improve with increasing doses of diltiazem, there was a negative trend for metoprolol. It is concluded that diltiazem, given as monotherapy to hypertensive patients, does not impair subjective well-being.
Adult↗
Antihypertensive effects of chronic 5-hydroxytryptamine (5-HT2) receptor blockade with irindalone in the spontaneously hypertensive rat.
The present study was conducted to evaluate the antihypertensive effects of irindalone, a potent 5-HT2-receptor blocking agent with weak alpha 1-adrenoceptorblocking properties. Young spontaneously hypertensive rats (SHR) received irindalone in the food (daily intake estimated to 10 mg/kg) for 10 weeks and older SHR received irindalone subcutaneously for 2 weeks (3 mg/kg/day by osmotic pump). The indirect systolic blood pressure was measured each week (tail plethysmography) and at the end of the intervention periods the direct intraarterial blood pressure was measured in conscious rats. Subsequently a dose-response curve of pressor responses to phenylephrine was constructed in pithed rats. Chronic oral treatment with irindalone reduced the development of hypertension but influenced neither body weight nor heart weight. The subcutaneous treatment with irindalone reduced the blood pressure in relatively older SHR compared with controls. Pressor responses to phenylephrine were antagonized in rats receiving oral treatment. However, during subcutaneous treatment with irindalone the dose-response curve to phenylephrine was not influenced, suggesting that the blood pressure reduction was not directly related to a concomitant alpha 1-adrenoceptor blockade. These results demonstrate that irindalone effectively reduces the blood pressure in SHR and that no tolerance develops to its antihypertensive effects. Since the blood pressure reduction, at least following subcutaneous treatment, was not directly related to a concomitant alpha 1-blockade, it is suggested that the 5-HT2-receptor blockade may be of relevance for the antihypertensive effect.
Adrenergic alpha-Antagonists↗
Exercise hemodynamics and myocardial metabolism during long-term beta-adrenergic blockade in severe heart failure.
Hemodynamics and myocardial metabolism at rest and during exercise were investigated in 21 patients with heart failure. The patients were evaluated before and after long-term treatment (14 +/- 7 months) with the beta-adrenergic blocking agent metoprolol. Clinical improvement with increased functional capacity occurred during treatment. Maximal work load increased by 25% (104 to 130 W; p less than 0.001). Hemodynamic data showed an increased cardiac index (3.8 to 4.6 liters/min per m2; p less than 0.02) during exercise. Pulmonary capillary wedge pressure decreased at rest (20 to 13 mm Hg; p less than 0.01) and during exercise (32 to 28 mm Hg; p = NS). Stroke volume index (30 to 39 g.m/m2; p less than 0.006) and stroke work index (28 to 46 g.m/m2; p less than 0.006) increased during exercise and long-term metoprolol treatment. The arterial norepinephrine concentration decreased at rest (3.72 to 2.19 nmol/liter; p less than 0.02) but not during exercise (13.2 to 11.1 nmol/liter; p = NS). The arterial-coronary sinus norepinephrine difference suggested a decrease in myocardial spillover during metoprolol treatment (-0.28 to -0.13 nmol/liter; p = NS at rest and -1.13 to -0.27 nmol/liter; p less than 0.05 during exercise). Coronary sinus blood flow was unchanged during treatment. Four patients produced myocardial lactate before the study, but none produced lactate after beta-blockade (p less than 0.05). There was no obvious improvement in a subgroup of patients with ischemic cardiomyopathy. In summary, there were signs of increased myocardial work load without higher metabolic costs after treatment with metoprolol.
Adrenergic beta-Antagonists↗
Blunted renal sodium excretion during acute saline loading in normotensive men with positive family histories of hypertension.
The natriuretic and intra-arterial blood pressure response to an acute saline load (1000 mL 0.9% NaCl), was studied in normotensive young men with positive (n = 11) and negative (n = 21) family histories of hypertension. The age-matched (36 +/- 5 years) control group with negative family histories of hypertension was subdivided into two groups, one matched for body mass index (BMI) to the subjects with positive family histories of hypertension (n = 10), and another lean control group (n = 11). Baseline blood pressure was significantly higher in subjects with positive family histories of hypertension and in controls matched for BMI as compared with lean controls. Sodium excretion increased in all three groups during the saline infusion, while subjects with positive family histories of hypertension disclosed a diminished natriuretic response as compared with the two control groups. Systolic blood pressure increased significantly during the saline load in subjects with positive family histories of hypertension, while in subjects with negative family histories of hypertension, no significant change in blood pressure was observed. Plasma renin activity, angiotensin II, serum aldosterone, plasma noradrenaline, blood volume, and ouabain-sensitive erythrocyte sodium efflux rate constant did not differ between the three groups at baseline. A significant negative correlation was found between baseline sodium excretion and sodium efflux rate constant in subjects with positive family histories of hypertension. We conclude that the subjects with positive family histories of hypertension exhibit a blunted natriuretic and an exaggerated blood pressure response to an acute saline load as compared with the two control groups with negative family histories of hypertension. This could be of neuronal and/or hormonal origin.
Adult↗
The CSF and plasma pharmacokinetics of sufentanil after intrathecal administration.
Eight patients (7 men and 1 woman, 45-68 yr old) scheduled to undergo thoracotomy were given, preoperatively, 15 micrograms sufentanil in the lumbar intrathecal space for a study of cerebrospinal fluid (CSF) and plasma kinetics of sufentanil. Multiple samples of plasma and CSF from the lumbar region were obtained through indwelling catheters for 12 h and analyzed for sufentanil by radioimmunoassay. Pharmacokinetic parameters were derived by noncompartmental analysis. In plasma, the maximal concentration of sufentanil appeared after 0.65 +/- 0.17 h (mean +/- SEM). No equilibrium was reached between the sufentanil concentration in CSF and plasma, but the CSF/plasma concentration ratio declined from approximately 140 at 2 h to about 15 at 10 h. Extrapolation indicates that another 10 h would be required before the concentration in CSF would equal that in plasma. The mean residence time (MRT) of sufentanil in CSF was 0.92 +/- 0.08 h and in plasma was 6.8 +/- 0.6 h. The volume of distribution at steady state (Vss) in the subarachnoid compartment was 1.54 +/- 0.39 ml/kg, and the clearance from the CSF was 27 +/- 5 microliters.kg-1.min-1. The intrathecal administration of 15 micrograms sufentanil at the beginning of the operation did not produce analgesia that lasted into the postoperative period. Most patients had urinary retention, but none experienced any serious complications. This study demonstrates that the lipophilic opioid sufentanil undergoes rapid clearance from CSF and absorption to plasma after intrathecal administration. These pharmacokinetic characteristics are slower for the less lipophilic opioids meperidine and morphine. The rapid pharmacokinetics of sufentanil explain its rapid onset of action and short-lasting effects.
Aged↗
Resting and volume-stimulated circulating atrial natriuretic peptide in young normotensive men with positive family histories of hypertension.
Normotensive young men (36 +/- 5 years old) with positive family histories of hypertension (n = 11) and age-matched controls (n = 21) with negative family histories of hypertension were examined. The control group was divided into one group matched for body mass index with those subjects with positive family histories (n = 10) and one group with normal body mass index (n = 11). Blood pressure, central venous pressure (CVP), plasma atrial natriuretic peptide (ANP) and serum aldosterone were examined at a baseline and during an acute volume load with 1000 ml saline solution. Subjects with positive family histories and controls matched for body mass index had a higher blood pressure at baseline than controls with normal body mass index. CVP and serum aldosterone did not differ between the three groups, while sodium intake and plasma concentrations of ANP were significantly higher in subjects with positive family histories. During volume loading, CVP increased significantly more in subjects with positive family histories as compared with the two control groups. A blunted response to ANP was observed during volume loading in subjects with positive family histories, while subjects in the two control groups demonstrated comparable and significant increases in circulating ANP. Serum aldosterone, however, decreased during volume loading in all three groups, with no difference between the groups. We conclude that normotensive subjects with positive family histories are characterized by increased basal concentrations of ANP and exhibit a blunted response to an acute volume load.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗