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

The renin-angiotensin system has an important role in maintaining elevated blood pressure levels in certain forms of experimental and human hypertension. Renin, an enzyme produced by the juxtaglomerular cells of the kidney, acts on a protein substrate found in the alpha 2-globulin fraction of the plasma to produce a decapeptide, angiotensin I. This decapeptide is not directly pressor, but on passage through the pulmonary circulation is converted to an octapeptide, angiotensin II, a very potent pressor substance which acts by causing constriction of arteriolar smooth muscle. In addition to its direct action which increases blood pressure, angiotensin II acts on the adrenal cortex to cause the release of the sodium-retaining hormone aldosterone. Recent evidence suggests that this action may be mediated by the heptapeptide, angiotensin III. Both renin and its protein substrate exist in multiple forms and renin may also exist as a high molecular-weight "pro-hormone," although the physiologic significance of these forms is not clear. The elucidation of the biochemistry of the renin-angiotensin system has provided us with inhibitors which allow the system to be blocked effectively in vivo. Thus, angiotensin antagonists such as Sar 1, IIe 8-angiotensin II and converting enzyme inhibitors such as BPP 9a (SQ 20881) have proved useful in the study of experimental and human hypertension.
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PMID:The biochemistry of the renin-angiotensin system and its role in hypertension. 19 Aug 80

To understand the role of the renin-angiotensin-aldosterone system in the pathogenesis of human hypertension, in serial studies we have blocked the system using three different pharmacologic probes: 1) reduction of renin secretion by administration of the beta receptor blocker, propranolol; 2) blockade of the action of angiotensin II by infusion of saralasin, a competitive antagonist of angiotensin II; and 3) blockade of the enzymatic conversion of angiotensin I to angiotensin II by infusing a nonapeptide competitive inhibitor. The depressor responses induced by either propranolol or the nonapeptide expose a significant to major involvement of excess renin--angiotensin in maintaining the hypertension of some 50 to 70% of common forms of hypertension including "essential" hypertension. This subgroup includes nearly all patients with high or "normal" renin--sodium profiles. The considerably lower estimates for a renin factor in essential hypertension suggested by saralasin testing now appear due to the partial agonism of this drug. Further studies are required to determine whether this relative or absolute excess of renin secretion is primarily involved in the hypertension and if not why it fails to shut itself off. Similar studies of normal subjects are also needed to determine whether renin support of blood pressure is proportionately greater or less than in hypertensive subjects. Meanwhile the validation provided by these three different pharmacologic probes portends a burgeoning clinical role for renin--sodium profiling not only in screening for renal and adrenal cortical hypertensions but also for characterizing the vasoconstrictor and volume elements involved in various individual patients and thus enabling more specific treatments of the various subtypes of essential hypertension.
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PMID:Blockade of renin or angiotensin for understanding human hypertension: a comparison of propranolol, saralasin and converting enzyme blockade. 19

1. Acute severe sodium subtraction (20-25% of total exchangeable sodium) before or during treatment with adrenocorticotrophic hormone (ACTH) does little to modify the increase in blood pressure induced by ACTH. 2. Chronic low salt diet, less than 5 mmol/day, abolishes the blood pressure increase, but the response can be restored by increasing the sodium intake to as little as 10 mmol/day. 3. 17alpha,20alpha-Dihydroxyprogesterone infused concurrently with other adrenal steroids will mimic ACTH hypertension and perhaps represents a new class of steroid capable of influencing blood pressure.
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PMID:Further unravelling of the causes of ACTH-induced hypertension in the sheep. 19 14

In two fractions obtained from the bovine A. coronaria adenylate cyclase activity was identified and characterized. The adenylate cyclase activity of the 75,000 X g sediment shows a pH optimum at 7.4. The temperature dependence of this adenylate cyclase activity is linear when represented in the Arrhenius plot, and an Arrhenius activation energy of 13.2 kcal Mol-1 can be calculated for the enzyme reaction. The Km-value of the enzyme to ATP is 6 +/- 0.6 - 10(-4) M. The adenylate cyclase activity of the 75,000 X g sediment can be stimulated by NaF. 5'AMP and adenosine inhibit the adenylate cyclase activity of the 75,000 X g sediment. With regard to the enzyme activity, Mn++ and Co++ replace Mg++, but not Ca++. The monovalentcations Na+ and K+ do not influence the adenylate cyclase activity. In a particulate fraction containing plasma membranes, adenylate cyclase activity was also identified. This adenylate cyclase activity can be stimulated by catecholamines, noradrenaline, and isoproterenol. This stimulation can, however, only be proved for the enzyme in the coronaries of 9-week-old and 2-year-old animals. The adenylate cyclase activity from the coronaries of adult animals is not affected by catecholamines. These findings are discussed with regard to hypertension frequently found in adult animals.
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PMID:[Proof of adenylate cyclase activity in the coronary artery of cattle]. 19 28

Chronic administration of small doses of prostaglandin-synthesis inhibitor indometacin against the background of a salt load or unilateral nephrectomy induces the development of arterial hypertension in rats. Arterial pressure increases (two fold on the average) on the 6th week of the experiment in 60-80% of the animals. Arterial hypertension developing against the background of a salt load is marked by retention of sodium in the organism and increase the intravascular volume, while that developing in unilateral nephrectomy--by increased sodium excretion and reduced intravascular volume. Depressed activity of the renin-angiotensin-aldosterone system and conspicious changes in the renal vascular channel are noted in both forms of arterial hypertension. It is assumed that disorders in the metabolism of cyclic nucleotides underlie the changes occurring in the renal vessels due to the effect of indometacin. Similar generalized changes in the peripheral vascular channel on the whole may be the cause of the increased vascular resistance and one of the causative factors of the hypertension development.
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PMID:[2 models of indomethacin-induced arterial hypertension in rats in chronic experiments]. 20 75

1. The haemodynamic effects of oral converting enzyme inhibitor (SQ 14225) were assessed in eight patients with severe essential or renovascular hypertension. 2. Mean arterial pressure fell (149 +/- 5 to 127 +/- 8 mmHg, P less than 0.02), because of a fall in total peripheral resistance (6.9 +/- 0.53 to 5.7 +/- 0.40 kPa 1(-1)s m2) without a significant change in cardiac index. Two of the eight patients were non-responders without pressure reduction or a haemodynamic change. Sodium restriction (10 mmol/day) while the same dose of SQ 14225 was continued further lowered arterial pressure (137 +/- 8 to 111 +/- 12 mmHg, P less than 0.05) through further resistance reduction (6.5 +/- 0.53 to 5.2 +/- 0.40 kPa 1(-1)s m2, P less than 0.05). 3. Haemodynamic responses to head-up tilt (increased heart rate and resistance, decreased cardiac index) were unaffected by SQ 14225 regardless of sodium intake. 4. The pattern of reduction in peripheral resistance, with unchanged cardiac index, was similar to that produced by vasodilators acting at both arteriolar and venular levels.
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PMID:Haemodynamics of orally-active converting enzyme inhibitor (SQ 14225) in hypertensive patients. 21 68

1. Pressor responses to angiotensin II, noradrenaline and tyramine were examined in sheep prior to and during the development of corticotrophin-induced hypertension. 2. Pressor responses to angiotensin II amide did not change with corticotrophin (ACTH) administration. Small significant increases in pressor responses to noradrenaline occurred at low doses only (0.27 and 1.06 mumol/h). Significant increases in response to tyramine occurred after 24h of ACTH administration, but were not maintained after 6 days of ACTH. These changes are quantitatively small and do not suggest that changes in pressor sensitivity contribute significantly to the rise in blood pressure following ACTH administration. 3. Sodium depletion significantly reduced the pressor responses to angiotensin II amide at all doses and to tyramine in the middle range only, but did not affect the responses to noradrenaline.
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PMID:The effect of corticotrophin (ACTH) administration on the pressor action of angiotensin II, noradrenaline and tyramine in sheep. 21 61

1. A single intravenous administration of rabbit tonin antiserum into one-kidney one-clip hypertensive rats restored blood pressure to normal in seven out of ten animals. There was little change in blood pressure in two-kidney one-clip hypertensive, uninephrectomized or sham-operated rats. 2. Infusion of tonin in control rats did not modify arterial blood pressure. However, in indomethacin salt-treated rats a marked increase in arterial blood pressure was observed under tonin infusion. 3. Plasma tonin activity was significantly increased in human essential and renovascular hypertension. 4. These findings strongly suggest that tonin is important in the maintenance of high blood pressure. However, other factors (possibly prostaglandins and sodium) have to be modified in order to activate the tonin--angiotensin II system.
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PMID:Tonin--angiotensin II system in hypertension. 21 73

1. Ouabain-sensitive uptake of 86Rb, a measure of the Na+-K+ pump activity, was studied in tail arteries of rats made hypertensive with deoxycorticosterone and saline. 2. Decreased activity of the ouabain-sensitive Na+-K+ pump supports the hypothesis that the activity of Na+-K+ pump is suppressed in volume expanded hypertension.
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PMID:Altered activity of the sodium-potassium pump in arteries of rats with steroid hypertension. 21 75

The effect of a 5 day ACTH test (40 U/24 h) on plasma aldosterone (aldo), deoxycorticosterone (DOC), plasma renin activity (PRA) and urinary excretion of aldosterone-pH1-conjugate (pH-1-aldo) and tetrahydro-DOC (TH-DOC) was investigated in 8 normotensive children (group I), 8 patients with hypertension of unknown origin (group II), and 4 hypertensive children with dexamethasone suppressible hyperaldosteronism (DSH) (group III). Changes in blood pressure and sodium balance were studied in all groups. Under baseline conditions there was no hormonal difference between group I and II. In contrast, the children in group III had a suppressed PRA and a 1.5--2 fold elevation of aldo and DOC. Plasma DOC and urinary THDOC increased continuously 10--50 fold in all groups during the ACTH test. Aldo rose transiently 2--4 fold on the first day of ACTH and fell subsequently below baseline levels in group I and II. The children with DSH (group III), however, showed an unusual, sustained aldo stimulation with ACTH. PRA decreased significantly after ACTH in group I and II. Sodium retention aTH administration. The highest blood pressure rise was observed in group III (from 124/72 to 139/90 mm Hg). The blood pressure response to ACTH was partly sodium dependent. Although aldo and DOC and sodium retention may contribute to the ACTH induced blood pressure elevation, other factors must play a role.
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PMID:Mineralocorticoids, salt balance and blood pressure after prolonged ACTH administration in juvenile hypertension. 21 19


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