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

An investigation of the relationship between nephrotensin and the renin angiotensin system was carred out. Nephrotensin was found in the plasma of rats with renal clip hypertension and with chemically induced kidney damage. There was no demonstrable correlation between presence of nephrotensin and plasma renin activity, and the pressor activity of nephrotensin was not altered by previous immunization of test animals with angiotensin II nor by pretreatment with angiotensin I converting enzyme inhibitor. These results indicate that nephrotensin is different from the components of the renin-angiotensin system.
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PMID:Differentiation of nephrotensin from the renin angiotensin system. 16 47

Seven patients with essential hypertension and seven patients with hypertension associated with renal artery stenosis received captopril (SQ 14225), an inhibitor of angiotensin I converting enzyme. There was a significant reduction in mean blood pressure, from 176/113 +/- 4/3 mm Hg during the control period to 140/90 +/- 5/3 mm Hg during captopril administration. Five patients received captopril alone and nine patients needed hydrochlorothiazide in addition to control their blood pressure. Captopril produced a significant increase in peripheral plasma renin activity. When measured 12 hours after the administration of captopril the angiotensin I converting enzyme activity was found to be similar to that during the control period even though the blood pressure was at or near normal. These findings indicate that although captopril is an effective antihypertensive agent, its action does not depend only on inhibition of plasma angiotensin I converting enzyme activity.
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PMID:Effect of captopril (SQ 14225) on blood pressure, plasma renin activity and angiotensin I converting enzyme activity. 22 56

Purified peptidyl dipeptidase (angiotensin I converting enzyme or kininase II) from human lung or hog kidney is inhibited by commercially prepared plasma protein preparations, by human serum albumin and by the additive albumin stabilizer, acetyltryptophan. After the initial steps of purification, albumin was detected by immunodiffusion as a component in human lung peptidyl dipeptidase preparation. Fragment C of albumin (sequence 124-298) is a more potent inhibitor than the parent molecule (Ki = 1.7 X 10(-5)M). Reduction and carboxymethylation of five of the six S-S bridges in Fragment C yield the most potent noncompetitive inhibitor (Ki = 3 X 10(-6)M). Reduction of the sixth bridge raises the K1. This indicates that maintenance of the tertiary structure in Fragment C is of importance for the inhibition. Neither albumin nor Fragment C are substrates of the enzyme. Fragment C and its derivative also inhibit the inactivation of bradykinin by the purified human enzyme and by the peptidyl dipeptidase on the surface of intact cultured human endothelial cells.
Hypertension
PMID:Inhibition of human peptidyl dipeptidase (angiotensin I converting enzyme: kininase II) by human serum albumin and its fragments. 23 85

1. The response of arterial blood pressure, plasma renin activity and plasma aldosterone concentration to inhibition of angiotensin I converting enzyme (kininase II) with captopril has been studied in patients with severe, treatment-resistant, malignant hypertension. 2. Nine patients with a past history of severe hypertension, supine diastolic blood pressure greater than 120 mmHg before conventional antihypertensive therapy and resistant to conventional antihypertensive therapy were studied. 3. Captopril administration resulted in a marked decrease in arterial blood pressure and plasma aldosterone concentration and an increase in plasma renin activity. 4. Although arterial blood pressure remained significantly below the values observed during the control period, pressure did tend to increase again after 3 days. Addition of hydrochlorothiazide kept arterial pressure significantly below pretreatment control values.
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PMID:Response of arterial blood pressure, plasma renin activity and plasma aldosterone concentration to long-term administration of captopril in patients with severe, treatment-resistant malignant hypertension. 39 84

We examined whether the renal protective effect of the angiotensin I converting enzyme inhibitor enalapril in stroke-prone spontaneously hypertensive rats (SHRSP) is dose-related and associated with alterations in the urinary excretion of prostaglandin (PG) E2 and 6-keto-PGF1 alpha, a stable breakdown product of prostacyclin. Enalapril maleate at 1.5, 5 and 15 mg/kg/day or vehicle was chronically administered to saline-drinking SHRSP (six per group) starting at 8.1 weeks of age. Vehicle-treated SHRSP developed severe hypertension, proteinuria and strokes (age at death, 14 +/- 1 weeks; mean +/- S.E.). Enalapril prolonged survival dose-dependently and reduced proteinuria; all SHRSP given 15 mg/kg/day lived beyond 23 weeks of age without evidence of stroke or proteinuria. There was no effect of enalapril at any dose on systolic arterial blood pressure in spite of variable levels of urinary protein excretion and onset of stroke in the different groups. Likewise, urinary 6-keto-PGF1 alpha and PGE2 excretion did not differ among the groups except for an increase in 6-keto-PGF1 alpha in the 15 mg/kg/day group at one week after initiation of enalapril therapy. These results are consistent with a dose-related renal protective action of enalapril in saline-drinking SHRSP that is not closely associated with sustained alterations in urinary excretion of renal vasodilatory PGs.
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PMID:The antiproteinuric action of enalapril in stroke-prone spontaneously hypertensive rats is unrelated to alterations in urinary prostaglandins. 154 1

Endothelin-1 (ET-1), a potent vasoconstrictor peptide synthesized by the vascular smooth muscle endothelium, has been previously shown to produce a sustained, salt-sensitive elevation in mean arterial pressure when chronically infused over a 7-day period into male Sprague-Dawley rats. In addition to other physiological actions, ET-1 has been shown to have potent effects on various renal functions, including renin production. Activation of the renin-angiotensin system, therefore, may contribute to the pressor response induced by ET-1. In this investigation, captopril ([2S]-1-[3-mercapto-2-methylpropionyl]-L-proline), a sulfhydryl-containing angiotensin I converting enzyme inhibitor, was chronically administered to endothelin-infused rats to elucidate the role of the renin-angiotensin system in this animal model of hypertension. Rats were catheterized, housed in metabolic cages, and maintained on a fixed 6.0 meq.day-1 sodium intake throughout the experiment, with daily measurements taken of mean arterial pressure, heart rate, water intake, urine output, and urinary sodium and potassium excretions. Infusion of ET-1 alone at a rate of 5.0 pmol.kg-1.min-1 for 7 days was associated with a significant and sustained increase in mean arterial pressure; concomitant chronic administration of captopril in another group of rats at a rate of 1.0 mg.kg-1.hr-1 prevented the ET-1-induced hypertension. In an additional study, however, increases in plasma angiotensin II concentration were not observed in rats administered ET-1 alone at 5.0 pmol.kg-1.min-1. These results indicate that endothelin-induced hypertension may involve stimulation of the renin-angiotensin system but not an increase in circulating angiotensin II concentration.
Hypertension 1992 Jun
PMID:Captopril prevents chronic hypertension produced by infusion of endothelin-1 in rats. 159 67

Inhibitors of two zinc metallopeptidases, angiotensin I converting enzyme (ACE) and neutral metalloendopeptidase-24.11 (EP-24.11), are antihypertensive agents. In this issue of Hypertension, Genden and Molineaux report that yet another peptidase inhibitor, metalloendopeptidase-24.15, EC 3.4.24.15 (EP-24.15), lowers blood pressure in normotensive rats. In this editorial we discuss the possible role of kinins as common mediators of part of the vasodepressor action of these peptidase inhibitors. Genden and Molineaux report that the marked fall in blood pressure caused by the EP-24.15 inhibitor is almost abolished by a kinin receptor antagonist, supporting the hypothesis that kinins play a role in the regulation of normal blood pressure. We have confirmed that the EP-24.15 inhibitor used by these investigators lowers blood pressure. Up to now, EP-24.15 has not been implicated in in vivo metabolism of kinins. Although a number of kininases have been identified, our own previous work indicated that the metabolic pathway responsible for clearing kinins from the circulation involves the action of kininase II (angiotensin I converting enzyme) and renal peptidases. Nevertheless, the main metabolic pathway involved some other unidentified enzyme, since in these experiments disappearance of kinins from the circulation was only marginally reduced by a "cocktail" of inhibitors of ACE, EP-24.11, and carboxypeptidase N. It could be that EP-24.15 is involved in kinin metabolism. However, a number of questions need to be answered with regard to the mechanism by which the EP-24.15 inhibitor lowers blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1991 Sep
PMID:Zinc metallopeptidase inhibitors. A novel antihypertensive treatment. 188 49

Hypertension was produced in cynomolgus monkeys by reducing blood flow to the left kidney by 60% via renal artery stenosis (2-kidney, 1-clip). Significant increases in mean arterial blood pressure (MABP) were observed within two to three weeks. Maximum increase (from 95 +/- 6 mmHg to 130 +/- 7 mmHg) occurred at about four to six weeks following renal artery stenosis and was sustained for more than 24 weeks. Plasma renin activity (PRA) was elevated concomitantly with the increase in MABP. PRA was raised to 42 +/- 3 ng angiotensin I/ml/hr six weeks after renal artery stenosis from a control PRA of 3 +/- 0.7 ng angiotensin I/ml/hr. At six months post renal artery stenosis, PRA was 33.4 +/- 4.2 ng angiotensin I/ml/hr. The angiotensin II (AII) receptor antagonist saralasin, the angiotensin I converting enzyme inhibitor captopril, and the renin inhibitor CGP 38,560 produced sustained reductions in MABP. The antihypertensive response to the renin inhibitor CGP 38,560 was associated with a reduction in PRA of greater than 99%, and a greater than 90% reduction in immunoreactive AII. These studies demonstrate that high-renin hypertension can be induced in the cynomolgus monkey. This pathological model provides a useful method for investigating the antihypertensive effects of agents which antagonize the renin-angiotensin system in a nonhuman primate.
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PMID:Development of a high renin model of hypertension in the cynomolgus monkey. 176 Aug 94

To study the effects of a novel angiotensin I converting enzyme inhibitor (ACEI) on hypertension-induced cardiac hypertrophy, benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4) at the dose of 3 and 10 mg/kg/d p.o. was administered to spontaneously hypertensive rats from 4 to 16 weeks of age. In addition to suppression of developing blood pressure, benazepril hydrochloride reduced both the wet weights of whole heart and left ventricle dose-dependently and significantly. Benazepril hydrochloride had no effect on hydroxyproline concentration and content or protein concentration in the left ventricle, whereas is reduced the total protein content dose-dependently. Serum ACE activity was significantly reduced at 10 mg/kg/d of benazepril hydrochloride, but renin activity, aldosterone and noradrenaline concentration in serum were not changed. From the microscopic findings of the left ventricle, benazepril hydrochloride reduced the myocardial hypertrophy significantly. From these results, benazepril hydrochloride seems to suppress the increase in volume load by acting through the renin-angiotensin-aldosterone system, and dose not seem to cause a significant reflex of catecholamine which often occurs with peripheral vessels dilation. Thus, benazepril hydrochloride may be expected to suppress cardiac hypertrophy in patients with hypertension.
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PMID:Effect of benazepril hydrochloride on cardiac hypertrophy in spontaneously hypertensive rats. 183 66

In the present study we examined whether the angiotensin I converting enzyme inhibitor, captopril, would protect stroke-prone spontaneously hypertensive rats (SHRSP) from stroke and renal pathology over a 26-week period. In the control group of six untreated SHRSP fed Stroke-Prone Rodent Diet and 1% NaCl drinking solution, all animals developed severe hypertension and stroke by 16.1 weeks of age. In eight salt-loaded SHRSP treated with oral captopril (50 mg/kg/day) beginning at 8.4 weeks of age, systolic blood pressure was slightly but temporarily suppressed and then continued to rise; by 12 weeks of age systolic blood pressure reached levels of severe hypertension, 240 +/- 8 mm Hg, and did not differ from that of untreated SHRSP. No deaths or brain lesions were noted in captopril-treated SHRSP despite severe hypertension maintained through 26 weeks of age when the study ended. Captopril treatment prevented increases in urinary protein excretion (14 +/- 2 v 63 +/- 16 mg/day at 11.7 weeks of age, P less than .01) and the severe brain, renal, and cardiac vascular lesions observed in untreated SHRSP. When maintained on Stroke-Prone Rodent Diet and saline, plasma renin activity of untreated SHRSP surviving until 14.5 weeks of age was markedly increased (29.1 +/- 9.4 ng Ang I/mL/h) compared with either untreated SHRSP (9.2 +/- 2.5 ng Ang I/mL/h, P less than .01) or Wistar-Kyoto rats (3.5 +/- 1.0 ng Ang I/mL/h, P less than .01) maintained on standard diet and water.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapeutic benefit of captopril in salt-loaded stroke-prone spontaneously hypertensive rats is independent of hypotensive effect. 193 Aug 50


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