Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stop-flow technique was used to determine the site of entry of kininase II into tubular fluid in dogs. Stop-flow patterns were constructed for kininase II, p-aminohippurate, sodium, and potassium. The proximal tubule was localized by the peak of p-aminohippurate concentration and the distal tubule by the minimum sodium concentration. In the stop-flow pattern for kininase II, three peaks (a, b, and c) were observed. A main peak (a), located 2.25 +/- 0.45 ml distal to the p-aminohippurate peak (p less than 0.01) and 3.75 +/- 0.31 ml proximal to the minimum sodium concentration (p less than 0.001), was observed in all experiments. Peak c, located 2.6 +/- 0.4 ml (p less than 0.01) proximal to the p-aminohippurate peak, was observed in five dogs. Peak b appeared in five dogs and was always located 2.0 ml distal to the minimum sodium concentration. This peak was coincident with the potassium peak. Only two of eight experiments showed all three peaks. These results showed that the major kininase II entry into the tubular fluid is near the p-aminohippurate peak and that distal entry occurred in 63% of the dogs.
Hypertension 1988 Feb
PMID:Site of entry of kininase II into renal tubular fluid. 283 Nov 47

To evaluate whether hypertension is a cause or just an association with diabetic renal disease, diabetes was induced in both normotensive Wistar-Kyoto and spontaneously hypertensive rats (WKY and SHR). Animals were assessed monthly for 8 months before sacrifice. When compared to normotensive diabetic rats (WKY-STZ), hypertensive diabetic rats (SHR-STZ) had an earlier and more rapid rise in urinary albumin excretion. In addition, SHR-STZ had increased glomerular basement membrane thickness when compared to WKY-STZ or SHR. In a separate experiment, Enalapril therapy (35 mg/L) was administered in drinking water to WKY-STZ and SHR-STZ. Enalapril significantly reduced blood pressure in both animal groups, and this was associated with a decrease in urinary albumin excretion. The SHR-STZ model has accelerated nephropathy as determined by both functional and structural parameters. Angiotensin-converting enzyme inhibition is associated with a reduction in albuminuria in both hypertensive and normotensive models of diabetic nephropathy.
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PMID:Genetic hypertension accelerates nephropathy in the streptozotocin diabetic rat. 283 66

The intrarenal kallikrein-kinin system was studied during the acute phase of renovascular hypertension induced by renal artery constriction and during teprotide inhibition of kininase II in the dog. Kallikrein-like activity measured by both kininogenase and esterolytic assays, was increased during renal artery constriction (p less than 0.5) and (p less than 0.01). The administration of teprotide resulted in a further increase of renal cortical kallikrein-like activity and inhibited kininase II activity (p less than 0.01). Following the inhibition of kininase II, the plasma concentration of kininogen was also significantly decreased (p less than 0.01). These results suggest that kininase II inhibition may increase levels of intrarenal and plasma kinins and that decreased degradation of kinin peptides may contribute significantly to the acute hypertensive effect of teprotide.
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PMID:Intrarenal kallikrein-kinin activity in acute renovascular hypertension in dogs. 285 35

Angiotensin-converting enzyme (ACE) inhibitors are a group of drugs recently introduced to treat hypertension and congestive heart failure. There are many reports of a dry cough in patients treated with (ACE) inhibitors, but this is often considered a rare side effect. Eleven of 30 patients treated with the investigational ACE inhibitor cilazapril complained about a chronic cough.
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PMID:Cough caused by cilazapril. 296 78

Angiotensin-converting enzyme (ACE) activity was measured in microvessels prepared from cerebral cortices of 4-week-old spontaneously hypertensive rats (SHR). The Vmax value of the ACE activity in the cerebral microvessels of SHR was lower than that of Wistar Kyoto controls of the same age by 25% without difference in Km value for substrate. The low activity of ACE in the cerebral microvessels of young SHR indicates that in this animal model of hypertension the function of ACE is genetically altered in the cerebral microvessels, which may be correlated with the alteration of the cerebral microcirculation and pathogenesis of hypertension.
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PMID:Low activity of angiotensin-converting enzyme in cerebral microvessels of young spontaneously hypertensive rats. 298 30

Angiotensin-converting enzyme (ACE) inhibitors are useful antihypertensive agents. Enalapril maleate is a new ACE inhibitor with actions similar to those of captopril but with fewer side-effects. A study was conducted on 19 black South Africans with mild or moderate essential hypertension; enalapril was compared with propranolol as monotherapy or together with hydrochlorothiazide in a 1-year randomized, double-blind, parallel study. Neither enalapril nor propranolol alone produced consistent, significant reductions in blood pressure. There were no significant differences between the blood pressure responses to enalapril and to propranolol (either with or without hydrochlorothiazide). It is concluded that neither enalapril nor propranolol is effective as monotherapy in the treatment of hypertension in South African blacks, but that both require the addition of a thiazide diuretic.
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PMID:Comparison of the antihypertensive effect of enalapril and propranolol in black South Africans. 298

The acute antihypertensive effect of a new long-acting oral angiotensin I-converting enzyme (ACE) inhibitor, enalapril maleate, was assessed in 20 hypertensive patients, of whom 14 had essential hypertension, 4 had renovascular hypertension, one had hypertension associated with chronic renal failure, and one had primary aldosteronism. Enalapril maleate significantly lowered the blood pressure in either low-renin or normal- and high-renin hypertensives. There was a significant correlation for all patients as a group between the pretreatment levels of serum ACE activity and the reduction in mean blood pressure (r = -0.454, p less than 0.05, n = 20) 2 h after drug administration. The serum ACE activity decreased maximally 3 to 4 hours after drug administration and did not return to baseline levels within 24 h. There was a significant correlation between the reduction in mean blood pressure and changes in ACE activity 90 min and 2 h after drug administration, respectively, for all patients as a group (r = 0.495, p less than 0.05, n = 20, at 90 min; r = 0.508, p less than 0.05, n = 20, at 2 h). The plasma renin activity (PRA) significantly increased in normal- and high-renin hypertensives but not in low-renin hypertensives. There was a close correlation between the reduction in mean blood pressure and the PRA 8 h after drug administration in normal- and high-renin patients (r = -0.623, p less than 0.05, n = 13), while no such relationship was observed in low-renin patients. The plasma aldosterone concentration (PAC) significantly decreased within 3 h, the lowest values occurring at 8 h after drug administration, and it returned to baseline levels within 24 h in all patients. No relationship was found between the reduction in mean blood pressure and changes in PAC after drug administration in either low-renin or normal- and high-renin hypertensives. The plasma bradykinin concentration (PBC) increased within 1 h, the highest values occurring at 3 h after drug administration, and returned to baseline levels within 24 h in low-renin hypertensives, while the PBC was significantly increased at 4 h and had not returned to baseline levels within 24 h in normal- and high-renin hypertensives. There was a significant correlation between percentage changes in mean blood pressure and those in PBC 90 min after drug administration in normal- and high-renin hypertensives (r = -0.556, p less than 0.05, n = 13), while no relationship was observed between them in low-renin hypertensives.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[The acute effects of the new angiotensin I-converting enzyme inhibitor, enalapril maleate, on blood pressure, plasma renin, aldosterone and kinins in hypertensive patients]. 299 Oct 35

Angiotensin-converting enzyme inhibitors promise to make important therapeutic contributions to the control of hypertension and congestive heart failure. The nonapeptide teprotide was the first of these inhibitors to be tested clinically. It was followed by orally active inhibitors, captopril in 1977 and enalapril in 1980. The latter is representative of a new design for the inhibition of metallopeptidases and is the subject of this review. The best of the N-carboxyalkyldipeptide inhibitors inhibits angiotensin-converting enzyme with a Ki of 7.6 X 10(-11) M. This compound is the most potent competitive inhibitor of a metallopeptidase yet to have been reported. The basis of this high potency is beginning to be understood and in part is considered to involve precisely arranged multiple interactions within the enzyme active site. X-ray crystallography of a thermolysin-inhibitor complex has been achieved. Assuming that similar interactions within the active site of angiotensin-converting enzyme are mechanistically probable, the authors hypothesize the binding of enalaprilat to converting enzyme as shown in Figure 24. Such interactions are consistent with kinetic studies (Section V) with the understanding that binding to the enzyme is not sensitive to the inhibitor's state of NH protonation. The reason for this surprising conclusion has not been established. Perhaps counterbalancing factors are involved in the energetics of binding or there may be compensating adjustments made in the enzyme which permit NH protonated and nonprotonated inhibitor to bind equally well. Figure 24 also summarizes present understanding of the conformation of enalaprilat when bound to angiotensin-converting enzyme. From studies on conformationally defined analogs of enalaprilat, it seems likely that the Ala-Pro segment of enalaprilat binds in a conformation that is close to a minimum energy conformer. This situation no doubt contributes to the potency of enalaprilat, since little binding energy would be needed to induce conformational changes in this part-structure of enalaprilat when it is bound to the enzyme. The phenethyl group of enalaprilat is believed to be near the alpha-hydrogen of the L-Ala residue in the enzyme-inhibitor complex. However, the synthesis of conformationally restricted analogs to establish this point has not yet been reached. The N-carboxyalkylpeptide design was developed from Wolfenden's collected product inhibitors of carboxypeptidase-A. Whether or not N-carboxyalkyldipeptides should be classified as collected product or transition state inhibitors is unclear.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The design and properties of N-carboxyalkyldipeptide inhibitors of angiotensin-converting enzyme. 299 4

It is now well recognised that the renin-angiotensin system plays a key role in the control of blood pressure not only through circulating angiotensin II but through its interaction with the autonomic and central nervous systems. Angiotensin-converting enzyme (ACE) inhibitors have proved to be effective in lowering blood pressure in different types of hypertension. This study evaluates the antihypertensive effects of enalapril, a new, potent, long acting ACE inhibitor. 50 patients with uncomplicated essential hypertension were included in 4 groups. Group I was used to compare the effects of enalapril and propranolol on blood pressure, renal function, plasma renin activity, aldosterone excretion and plasma lipids in 24 patients after 23 weeks. Group II was used to evaluate long term effects (48 weeks) of these drugs in 13 patients. Group III included 32 patients that received enalapril as monotherapy for 6 to 12 weeks. Group IV was studied to estimate the antihypertensive effect of low doses of hydrochlorothiazide in 18 patients receiving enalapril. The effect on mean blood pressure was similar with enalapril and propranolol (enalapril 117 versus 103 mm Hg and propranolol 115 versus 104 mm Hg); however, the glomerular filtration rate decreased with propranolol (105 versus 87 ml/min; p less than 0.05) and was unaltered with enalapril (102 versus 98 ml/min). Triglycerides rose with propranolol (179 versus 231 mg/dl; p less than 0.05) and did not change with enalapril (157 versus 121 mg/dl). In the long term, antihypertensive effects were similar and no significant side effects were observed. In 14/32 patients blood pressure became normal with enalapril alone. Low doses of hydrochlorothiazide (12.5 to 25 mg) decreased mean blood pressure by 10mm Hg when added to enalapril. The antihypertensive effect of enalapril was similar to that of propranolol; however, the lowering effect on glomerular filtration rate of propranolol did not occur with enalapril. A slight rise in triglycerides occurred only with propranolol. No significant side effects were observed with either propranolol or enalapril. Used as monotherapy, enalapril normalised blood pressure in 44% of cases. Addition of low doses of hydrochlorothiazide significantly increased the antihypertensive effect of enalapril.
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PMID:Enalapril in essential hypertension. 299 86

Angiotensin-converting enzyme (ACE) activity in the pituitary zone and 7 other brain areas has been studied in rats with developing spontaneous hereditary hypertension. ACE activity was significantly different in normotensive and spontaneously hypertensive rats, with the differences most prominent in pituitary body, cerebellum, striatum and medulla oblongata. Age-dependent variability in ACE activity was demonstrated.
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PMID:[Regional changes in the activity of the angiotensin-converting enzyme in the brain of rats with developing hereditarily induced hypertension]. 300 Apr 69


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