Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The acute effects of the kallikrein inhibitor aprotinin (498 ki.u./min), and the kininase II inhibitor SQ 14,225 (250 MICROGRAM), GIVEN INTRAVEnously during saralasin-induced angiotensin blockade, were studied in conscious sham-operated rats and rats with benign and malignant two-kidney, one-clip Goldblatt hypertension during dietary sodium restriction. 2. The blood pressure of conscious sham-operated rats increased significantly in response to aprotinin. It remained unchanged after SQ 14,225 in contrast to the significant vasodepressor effect seen when SQ 14,225 was given to the same rats under surgical stress and pentobarbital anaesthesia. 3. Benignly hypertensive rats showed a consistent vasopressor response to aprotinin and a marked vasodepressor response to SQ 14,225. The effects of both inhibitors were markedly and significantly blunted in malignantly hypertensive rats. 4. Our demonstration that two agents with known opposite actions on the kallikrein-kinin system produced predictable and opposite effects on blood pressure may indicate that this system is involved in the homeostatic regulation of blood pressure. It may play an important antihypertensive role in benign two-kidney, one-clip Goldblatt hypertension, a role which might be impaired in malignant hypertension.
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PMID:The kallikrein-kinin system in blood pressure homeostasis. 9 77

Goat antibodies developed against pure rabbit pulmonary angiotensin-converting enzyme (peptidyl dipeptidase, EC 3.4.15.1) were administered intravenously to rats with two-kidney Goldblatt hypertension and to normotensive animals. In the hypertensive model these antibodies were associated with a sustained, immune-dependent decrease of blood pressure to normal values. A smaller, but also immune-specific, reduction of blood pressure was observed in the normotensive group. The data suggest that heterologous antibody directed against angiotensin-converting enzyme may provide a biologically specific probe for examining the contribution of the renin-angiotensin system to normal and pathologic circulatory states.
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PMID:Reversal of renovascular hypertension by antibodies specific for angiotensin-converting enzyme. 21 95

Evidence from animal studies demonstrates that the renin-angiotensin (ANG II) system and sodium retention play major roles in experimental renovascular hypertension (RVH). Two basic models have been described. In the first, one-clip two-kidney Goldblatt hypertension, the ischemic kidney secretes renin, which leads to increased ANG II formation and hence elevation of blood pressure (BP). As BP rises, sodium excretion by the intact contralateral kidney increases (pressure natriuresis); therefore, there is no sodium retention. In the second, one-clip one-kidney Goldblatt hypertension, the contralateral kidney is removed. In this case the pressure natriuresis can no longer occur, and sodium retention occurs. The ensuing expansion of plasma volume inhibits renin secretion, so that in this model the renin level is normal or low. Following the clipping of the renal artery, renal blood flow and pressure are maintained distal to the stenosis by an ANG II-mediated vasoconstriction. This acts preferentially on the efferent glomerular arterioles, so that the ratio of preglomerular to postglomerular resistance is reduced, which helps to maintain glomerular filtration despite the reduced renal perfusion pressure. In the contralateral kidney the afferent arteriolar resistance is increased, probably as a direct result of exposure to the higher intrarenal arterial pressure. ANG II constricts the efferent arterioles in the same way as in the ischemic kidney, so that the ratio of preglomerular to postglomerular resistance is unchanged. When an angiotensin converting enzyme (ACE) inhibitor is given, the efferent arterioles vasodilate. In the ischemic kidney this may produce a reduction of glomerular filtration rate (GFR), which is not seen in the contralateral kidney. Unilateral RVH in humans corresponds closely to the animal model of one-clip two-kidney hypertension. Plasma renin activity is usually high, and converting enzyme inhibitors lower BP effectively. The increased renin is due exclusively to increased secretion of renin by the ischemic kidney, and is completely suppressed in the contralateral kidney. It is not clear whether bilateral RVH corresponds to the one-clip one-kidney model, but there is circumstantial evidence to suggest that both renin and volume factors may be involved. The majority of cases of human RVH are caused by atheroma, which is commonly bilateral, or by fibromuscular dysplasia. The former tends to be associated with atheroma elsewhere in the arterial tree, and often progresses to complete occlusion and renal failure. The latter occurs in younger patients, and almost never progresses to complete occlusion.
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PMID:Renovascular hypertension: etiology and pathophysiology. 265 13

In nuclear medicine new trends in the diagnosis of renal function are based on the introduction of new radiopharmaceuticals, improvements in the methodological part of the procedure and precise pharmacological intervention in response to given indications. Tc99m mercaptoacetyltriglycine (Tc99m MAG3) was tested as replacement for I123 orthoiodohippuric acid (I123 oIH) both in the form of a HPLC purified substance and as an impure kit preparation. HPLC purified Tc99m MAG3 clearance determinations in anuric patients showed a low extrarenal excretion amounting to only about 5% of the total clearance in normal patients. Kit preparations yielded about 90% of the labelled product; impurities were pertechnetate, reduced hydrolyzed Tc99m and chemically unidentified labelled products which showed a significantly lower renal, but increased hepatobiliary excretion in comparison with Tc99m MAG3. The renal clearance with kit preparations of Tc99m MAG3 was 55% of the clearance with oIH at a comparable urinary excretion. Significantly higher protein binding and therefore, a decrease in the distribution volume of Tc99m was found in comparison with I123 oIH. No difference was recorded between the two substances with respect to the renogram curves in normal subjects, apart from a modest delay in the elimination of Tc99m MAG3. For clinical purposes kit preparations of Tc99m MAG3 proved equal to I123 oIH. The influence of angiotensin converting enzyme (ACE) inhibitors (captopril) leads to characteristic changes in the renograms of patients with Goldblatt hypertension. Quantitative criteria for the evidence of haemodynamically significant renal artery stenosis were derived from investigations without and with captopril (25 mg) (I123 oIH and Tc99m DTPA) in 21 patients with essential hypertension. The criteria were defined as follows: a delay in peak activity (Tmax) in the I123 oIH captopril renogram exceeding 2 minutes as compared with the baseline value and/or a lower uptake of Tc99m DTPA in comparison with the uptake of I123 oIH (uptake quotient I123 oIH/Tc99m DTPA greater than 1.2). The diagnostic and prognostic potential of the captopril renogram was compared with that of the captopril test by investigating 34 patients with renal artery stenosis (23 uni-, 11 bilateral) (atherosclerosis: 23, fibromuscular hyperplasia: 11). The captopril renogram was positive more often (n = 12) than the captopril test (n = 4) in patients without renal functional impairment of the stenosed kidney. Similar results were obtained with both methods in patients with atrophic kidneys: captopril renography was positive in all cases with a positive captopril test.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[New aspects of nuclear medicine diagnosis of kidney function: improved potential by pharmacologic intervention and quantitative analytic procedures]. 297 26

Increased glomerular capillary pressure (GCP) mediates glomerular damage in hypertension. The efficacy of captopril, an angiotensin converting enzyme (ACE) inhibitor, and captopril-hydrochlorothiazide (captopril-TZ) in lowering GCP and preventing glomerular damage was evaluated in rats with two-kidney, one clip (2K, 1C) Goldblatt hypertension and partial ablation of the unclipped kidney. Thirty days after surgery nine rats received captopril, 11 received captopril-TZ and eight served as untreated control rats. Sixty days later systemic hypertension was associated with increased GCP and severe structural damage in the unclipped kidney of C rats. Captopril lowered arterial pressure (AP), and prevented the rise in GCP and structural lesion. Captopril-TZ decreased AP and GCP to a greater extent, but did not reduce structural damage further. Captopril lowered GCP, preventing structural damage; greater reduction of GCP with captopril-TZ did not provide further protection.
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PMID:Effect of captopril and hydrochlorothiazide on glomerular haemodynamics and histological damage in Goldblatt hypertension with partial renal ablation. 355 76

Captopril was administered to acute (8 to 14 days after unilateral renal artery constriction) and chronic (71 to 127 days after the constriction) two-kidney Goldblatt hypertensive dogs, and to normotensive ones for 21 days (oral administration of 10, 20 and 40 mg/kg/day, consecutively each 7-day period). The decrease of arterial blood pressure was remarkable in hypertensive animals with high plasma renin activity, but not in the normotensive animals. In the acute stage of hypertension, the antihypertensive effect of captopril was dose-dependent and persistent even after its cessation. In the chronic stage of hypertension, blood pressure also decreased, but the response was not dose-dependent and did not continue after cessation. Plasma renin activity rose in both hypertensive and normotensive animals during the treatment with captopril. There were no significant changes in heart rate, daily urinary volume, sodium balance, and renal clearances of sodium (CNa), potassium (CK), chloride (CCl) and creatinine (CCr). Circulating blood volume was also not altered. These results indicate that the main mechanism of antihypertensive effect of captopril in two-kidney Goldblatt hypertensive dogs is an inhibition of the angiotensin converting enzyme. In addition, the different effects in the acute and chronic hypertensive dogs suggest that some differences exist in the mechanism(s) of maintaining blood pressure between the two stages of two-kidney Goldblatt hypertension in dogs.
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PMID:Different effects of captopril on blood pressure in the acute and chronic two-kidney Goldblatt hypertensive dogs. 704 89