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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atrial natriuretic factor (ANF) is degraded by neutral endopeptidase. We hypothesized that neutral endopeptidase inhibition (NEP-I) increases sodium excretion and that this effect would be potentiated in the presence of an isolated increase in intrarenal ANF. In seven anesthetized dogs, ANF was infused into one renal artery to produce pathophysiologic concentrations in the supplemented kidney while the control kidney received physiologic circulating concentrations of ANF. In the control kidney, NEP-I (SQ 28,603) produced significant increases in urine flow, absolute sodium excretion and fractional sodium excretion while glomerular filtration rate (GFR) remained constant. These renal actions of NEP-I were associated with marked increases in urinary excretion of ANF and cyclic GMP consistent with decreased renal degradation and increased biologic activity of ANF. All of these effects were significantly greater in the supplemented kidney. The present study suggests that NEP-I produces natriuresis which appears to be independent of changes in GFR. In addition, while NEP-I mimics the renal action of pathophysiologic levels of ANF, NEP-I also potentiates the natriuretic effects of pathophysiologic concentrations of ANF as observed in congestive heart failure or hypertension.
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PMID:Neutral endopeptidase inhibition potentiates the renal actions of atrial natriuretic factor. 214 48

The effects of an orally active inhibitor (UK 79300) of the neutral metalloendopeptidase EC 3.4.24.11 were investigated in six healthy male volunteers maintained on a constant diet (150 mmol sodium/day and 80 mmol potassium/day). Subjects were studied in a random order, single-blind study on two occasions, each 48 hours in length, when they were given UK 79300 (25 or 50 mg p.o.) or placebo at 12-hour intervals (each agent for 24 hours). The endopeptidase inhibitor enhanced plasma concentrations of atrial natriuretic factor in association with suppression of both plasma renin activity and aldosterone concentrations. Twenty-four-hour urinary excretion of sodium was doubled by UK 79300, and the urinary excretion rates of phosphorus, atrial natriuretic factor immunoreactivity, and cyclic guanosine monophosphate were also significantly enhanced, whereas urinary aldosterone excretion was halved. The profile of biological effects closely paralleled those previously reported with low dose infusions of atrial natriuretic factor in humans and animals. Therapeutic trials of such inhibitors are now indicated for hypertension or heart failure together with further studies to clarify the underlying mechanisms of action.
Hypertension 1990 Sep
PMID:Inhibition of endopeptidase EC 24.11 in humans. Renal and endocrine effects. 214 60

Chronic regulation of the cardiovascular system by atrial natriuretic factor was investigated by generating transgenic mice with elevated hormone levels in the systemic circulation. A fusion gene comprising the mouse transthyretin promoter and mouse atrial natriuretic factor structural sequences was designed so as to target hormone expression to the liver. Hepatic expression of atrial natriuretic factor was detectable as early as embryonic day 15 in transgenic animals. In adult transgenic mice, plasma immunoreactive atrial natriuretic factor concentration was elevated at least eightfold as compared with nontransgenic littermates. The mean arterial pressure of conscious transgenic mice was 75.5 +/- 0.9 mm Hg, significantly less than that of nontransgenic siblings (103.9 +/- 2.0 mm Hg). This difference in mean arterial pressure was not accompanied by significant changes in several other physiological parameters, including heart rate, plasma and urinary electrolytes, water intake, and urine volume. This study demonstrates that a chronic elevation of plasma atrial natriuretic factor decreases arterial blood pressure without inducing diuresis and natriuresis in transgenic mice and also illustrates the value of the transgenic approach for the study of the cardiovascular system.
Hypertension 1990 Sep
PMID:Hypotension in transgenic mice expressing atrial natriuretic factor fusion genes. 214 62

Hypoxia causes the release of atrial natriuretic factor (ANF), but the mechanisms are not yet understood. This study examined the relative contribution of pulmonary arterial hypertension, neural pathways, increased heart rate, or increased atrial size to the ANF response. Alveolar hypoxia [fractional concentration of O2 in inspired gas (FIo2) = 0.1] or pulmonary arterial hypertension (25-45 mmHg) was induced for 10 min in four series (n = 4-12 each) of anesthetized, mechanically ventilated pigs. During hypoxia, plasma ANF concentrations increased by 129 +/- 52 (SE) pg/ml (or 271 +/- 105%) over baseline (35 +/- 7 pg/ml; P less than 0.01) (series 1). There was also a significant increase of pulmonary arterial pressure, heart rate, central venous pressure, and pulmonary capillary wedge pressure. Repeated pulmonary hypertension induced by intravenous air infusion caused a repeated and reversible 125 +/- 14% increase (P less than 0.001) of plasma ANF, and this response was totally abolished by lesion of the cervical vagosympathetic trunks (series 2). Lesion of these nerves 1 h before hypoxia also decreased the ANF response to hypoxia by 45-58% (P less than 0.01), whereas responses of heart rate and atrial pressures were unchanged (series 3). The ANF response to hypoxia, expressed in percent of baseline, was not affected by 0.2 mg/kg propranolol (PR) (no PR: 145 +/- 63%; PR: 151 +/- 82%; not significantly different from series 1 and control, series 3), although the increase in heart rate (no PR: 61 +/- 15 beats/min) was almost abolished (PR: 17 +/- 5 beats/min) (series 4). Hypoxia caused no significant changes in right and left atrial peak volume regardless of propranolol, as measured with an electrical conductance catheter. The results indicate that a new neural reflex of probably pulmonary arterial origin mediates approximately 50% of the ANF response to hypoxia. The remaining ANF response remains to be explored further and cannot be explained by conventional release mechanisms such as atrial stretch and pulsatility alone.
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PMID:Neural control of ANF release in hypoxia and pulmonary hypertension. 214

To evaluate the hypothesis of an atrial natriuretic factor (ANF) deficiency in hypertension-prone humans, we investigated plasma ANF and other variables in 116 white offspring of normotensive parents (ONorm) or essential hypertensive parents (OHyp). Ten ONorm and 10 OHyp, all men matched for age and body habitus, were studied after 4 days of low (70 mmol/day) and high (350 mmol/day) dietary sodium intake. After mild sodium restriction, plasma ANF did not differ between ONorm and OHyp (9.7 +/- 0.7 vs. 9.0 +/- 1.3 fmol/L). On high sodium intake, plasma ANF increased in ONorm, but not in OHyp (to 18.3 +/- 1.7 vs. 11.7 +/- 1.7 fmol/L; P less than 0.001). On the other hand, acute responses of plasma immunoreactive ANF (irANF) to saline loading or a norepinephrine-induced rise in blood pressure did not differ significantly between 8 ONorm and 8 OHyp. Fifty-one additional ONorm and 45 OHyp were evaluated during liberal sodium intake. Groups were further subdivided according to whether 24-h urinary sodium excretion was 91 mmol/m2 or less (modest salt intake) or more than 91 mmol/m2 (high salt intake). Twenty-four-hour urinary sodium was similar in the 26 ONorm and 21 OHyp on a modest salt intake (121 +/- 6 vs. 116 +/- 9 mmol) and in the 25 ONorm and the 24 OHyp on a high salt intake (226 +/- 10 vs. 221 +/- 9 mmol). However, compared with ONorm, plasma irANF in OHyp was slightly lower on modest sodium intake (7.7 +/- 0.7 vs. 5.3 +/- 0.7 fmol/L; P less than 0.05) and markedly reduced on high sodium intake (15.0 +/- 1.3 vs. 8.0 +/- 1.3 fmol/L; P less than 0.001). Moreover, the slope of the relationship between plasma irANF and 24-h urinary sodium was flatter in OHyp than in ONorm (z test = 2.4). We postulate a new endocrine syndrome characterized by a relative plasma ANF deficiency during high sodium intake in some hypertension-prone humans. This functional defect becomes apparent during chronic, rather than acute, stimulation of ANF release. It occurs as a familial disturbance and may potentially predispose to the development of hypertension.
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PMID:Dysregulation of atrial natriuretic factor in hypertension-prone man. 214 58

1. The pharmacokinetics and pharmacodynamics of quinapril and its active metabolite quinaprilat were studied in 20 subjects with renal function varying from normal to severe renal failure, during the approach to and at steady-state, and for 72 h after cessation of quinapril 20 mg orally for 7 days. 2. The apparent oral plasma clearance of quinaprilat (dose of quinapril equivalent/AUC of quinaprilat) was directly related to creatinine clearance (CLCr). The predicted apparent oral clearance of quinaprilat was zero when CLCr was zero, suggesting minimal extrarenal elimination. 3. Peak and trough concentrations of quinaprilat, and its apparent elimination half-life, varied inversely with CLCr. 4. Trough concentrations of quinaprilat showed no accumulation between 2 and 7 days, even in severe renal impairment. 5. There was a weak relationship between the oral plasma clearance of quinapril and CLCr. 6. ACE inhibition was marked and prolonged in all subjects, with 50% inhibition at 2.7 +/- 1.9% ng ml-1 of quinaprilat. The time for which ACE inhibition was greater than 90% was related inversely to CLCr. 7. Aldosterone concentrations and plasma renin activity responded in a predictable way, but with no clear relationship To CLCr. 8. Atrial natriuretic peptide concentrations were not affected by quinapril administration. 9. Glomerular filtration rate, as measured by Tc99mDTPA clearance, was not affected by quinapril administration. 10. Blood pressure at steady-state decreased significantly in the subjects with hypertension. The changes in blood pressure were not related to renal function. 11. These results suggest that the dosage rate of quinapril may have to be altered in renal impairment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pharmacokinetics and pharmacodynamics of quinapril and quinaprilat in renal impairment. 214 94

The endopeptidase EC 3.4.24.11 (atriopeptidase) degrades atrial natriuretic factor (ANF). Intravenous administration of UK 69,578 (0.025 to 10.0 mg/kg), a new specific atriopeptidase inhibitor, in 16 normal volunteers produced a two- to three-fold rise in endogenous ANF. Peak levels were reached within 2 h declining to control values by 8 h. The rise in ANF was associated with an increase in urine volume and mean urinary sodium excretion rose from 64.9 mmoles/8 h after placebo to 116.1 mmoles/8 h after 10 mg/kg UK 69,578. Despite the natriuresis, plasma active renin concentration was suppressed for up to 8 h. We conclude that inhibition of the endopeptidase EC 3.4.24.11 in humans elevates endogenous ANF and causes a natriuresis and may offer a novel therapeutic approach to the treatment of hypertension and cardiac failure.
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PMID:The atriopeptidase inhibitor UK 69,578 increases atrial natriuretic factor and causes a natriuresis in normal humans. 214 71

In order to define the factors responsible for cardiac hypertrophy in elderly hypertension, blood pressures and non-hemodynamic humoral parameters were correlated with echocardiographic left ventricular mass (LVM) in 30 elderly hypertensive patients and 30 age-matched normotensive subjects with a mean age of 65 years. Arterial blood pressures were obtained either at the clinic, after supine rest, during maximal exercise test, or with a 24 hour ambulatory monitoring device at 10 minute intervals. Interventricular septum and posterior wall thickness, but not end-diastolic diameter, were significantly increased in the hypertensives than in the normotensives. LVM was significantly correlated with all of te blood pressure parameters, having the strongest association with the mean of ambulatory systolic blood pressures (r = 0.65, p less than 0.001). On the other hand, plasma norepinephrine (r = 0.09), plasma renin activity (r = -0.14), and atrial natriuretic factor (r = -0.08), though known to influence cardiac adaptation to hypertrophy in young or middle aged hypertensives, were not correlated wit LVM. These results suggest that the heart in elderly hypertension is characterized by concentric hypertrophy, the only significant determinant of which appears to be a hemodynamic factor. Unlike younger patients, sympathetic nervous and renin-angiotensin systems may not play an important role in the development of cardiac hypertrophy in the elderly.
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PMID:[Determinant of cardiac hypertrophy in elderly hypertension]. 214 25

A prospective longitudinal study of 25 pregnant women (30 pregnancies) with chronic hypertension, a group prone to development of preeclampsia, was conducted to explore the relationship between the renin-angiotensin-aldosterone system and the development of superimposed preeclampsia. In women with chronic hypertension in whom preeclampsia did not develop (17 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated, beginning in the first trimester and continuing throughout pregnancy as found previously in normotensive pregnant women (n = 58). Plasma estradiol and progesterone levels also increased progressively. In women with chronic hypertension in whom preeclampsia developed (13 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated in the first trimester as in the other groups. However, later in pregnancy significant differences were observed. Blood pressure began to rise in the second trimester. Initially the renin-angiotensin-aldosterone system remained stimulated, but in the early third trimester, when preeclampsia was diagnosed, plasma renin activity and urine aldosterone excretion decreased, and atrial natriuretic factor increased. These data provide information that may be useful in the recognition of superimposed preeclampsia, and in the investigation of its pathogenesis.
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PMID:Longitudinal study of the renin-angiotensin-aldosterone system in hypertensive pregnant women: deviations related to the development of superimposed preeclampsia. 183 99

The effect of a single oral dose (50 mg) of captopril was studied in 12 hypertensive patients divided into 2 groups: 6 had a normal hemodynamic profile; the other 6 had NYHA class III or IV heart failure. Medical history and clinical and laboratory investigation showed that the heart failure was due exclusively to arterial hypertension. Mean arterial pressure (MAP), aldosterone, plasma renin activity (PRA) and atrial natriuretic factor (ANF) were followed for 4 hours after administration of captopril. MAP values showed a similar decrease in the 2 groups but the variations in the 3 hormones were much greater in the second group. This group showed higher basal levels of PRA, aldosterone and ANF; after stimulation PRA increased sharply preceded by a substantial decrease in aldosterone and ANF. To explain this phenomenon, the Authors propose that the liver of the patients with heart failure is unable to rapidly compensate the reduction in synthesis of angiotensin II caused by the drug with a corresponding increase in angiotensinogen production; the consequent sharp drop in plasma aldosterone would lead to a rise in renin production by the kidney. The arteriolar and venous vasodilatation induced by the ACE-inhibitor, would explain the drop in intra-atrial pressure with reduced plasma levels of ANF. The decrease in ANF could also be caused by the inhibition of the renin-angiotensin system of the heart leading to improved blood supply and hence myocardial contractility.
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PMID:[Captopril and hypertensive cardiopathy : therapeutic effects and hormonal changes]. 215 Mar 43


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