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

The antihypertensive effect and tolerability of enalaprilat, an intravenously administered angiotensin converting enzyme inhibitor, was studied in 65 patients with moderate or severe hypertension. In this randomized, double-blind study, enalaprilat was compared with placebo in 42 (22 enalaprilat, 20 placebo) moderate hypertensive (diastolic blood pressure [BP] 100 to 114 mm Hg) patients. It was compared with furosemide in 23 (12 enalaprilat, 11 furosemide) severe hypertensive (diastolic BP 115 to 130 mm Hg) patients. Enalaprilat (1.25 or 5.0 mg), placebo (5% dextrose) or furosemide (40 or 80 mg) was given every 6 hours intravenously up to 48 hours. In the moderate hypertension stratum, the mean supine diastolic BP was significantly (p less than or equal to 0.01) reduced from baseline at all timepoints in the enalaprilat group. These diastolic BP reductions were significantly (p less than or equal to 0.01) greater in the enalaprilat group than the placebo at 1 to 24 hours (-12 vs -4 mm Hg), with 59% of the patients responding to enalaprilat compared with 30% of the patients responding to placebo. An even greater reduction (p less than or equal to 0.01) was seen at 25 to 48 hours (-14 vs -7 mm Hg, with 73% enalaprilat vs 58% placebo responders). Significant (p less than or equal to 0.01) reductions in mean, supine systolic BP were also seen at 1 to 24 hours (-22 vs -2 mm Hg) and 25 to 48 hours (-24 vs -8 mm Hg) during the 48 hours of the double-blind treatment phase in the enalaprilat group compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of intravenous enalaprilat in moderate and severe systemic hypertension. 284 22

The development of hypertension in the spontaneously hypertensive rat (SHR) up to 8 weeks of age involves sodium retention with reduced fractional sodium excretion. Since angiotensin II (Ang II) directly stimulates proximal tubular sodium transport, we investigated age-related changes in proximal reabsorption (Jv), using shrinking split-drop micropuncture before and after enalaprilat in SHR at 5, 7 and 12 weeks of age and in age-matched Wistar-Kyoto rats (WKY). Control values for Jv were higher in the SHR than in WKY at 5 weeks, but lower at 7 and 12 weeks, consistent with an early phase of sodium retention. Enalaprilat reduced mean Jv by approximately 15% in all WKY groups, indicating the extent of Ang II-stimulated transport. In the SHR there was an age-dependent reduction in the effect of enalaprilat on Jv, and by 12 weeks no Ang II stimulation could be detected. Age-related changes in proximal tubular reabsorption could contribute to sodium retention in the young SHR and may reflect a more general pattern of inherited transport defects.
 ...
PMID:Age-related changes in angiotensin II-stimulated proximal tubule fluid reabsorption in the spontaneously hypertensive rat. 285 52

Enalaprilat (MK-422), an intravenously administered angiotensin-converting enzyme inhibitor, which is the parent compound of the oral angiotensin-converting enzyme inhibitor enalapril (MK-421), was studied in 11 patients with asymptomatic accelerated hypertension. Each patient received an initial intravenous dose of 1 mg, followed at one-hour intervals by enalaprilat 10 mg, furosemide 40 mg, and enalaprilat 40 mg. Six of 11 patients responded with a drop in mean arterial pressure greater than 15 mm Hg to diastolic levels below 110 mm Hg; there were four partial responders and one nonresponder. Pretreatment renins were not predictive of blood pressure response. No patient had any adverse reaction to the drug; there were no significant changes in posttreatment laboratory values. We conclude that enalaprilat is an effective, well-tolerated agent for the treatment of uncomplicated accelerated hypertension and its use does not imperil nonresponding uncomplicated patients.
 ...
PMID:Enalaprilat in hypertensive emergencies. 300 76

A multicenter, double-blind, placebo-controlled, randomized trial of fish oil in proteinuric patients with IgA nephropathy is being conducted by the Mayo Nephrology Collaborative Group. We completed enrollment of 106 patients into the trial in December 1991. The treatment period is for two years. Hypertension is being managed in all patients with enalapril maleate (Vasotec). We evaluated the associations between a variety of clinical and renal morphologic features and renal function at the entry of all enrolled patients. Among 78 males and 28 females [age(mean +/- SD) 36 +/- 14 years], older age at treatment randomization, hypertension, at disease discovery as well as at study entry, increased fractional excretion of albumin, increased serum triglyceride levels, and more severe tubulointerstitial, vascular, and combined glomerular and tubulointerstitial histologic lesions were all univariately associated (p < or = 0.01) with poorer renal function measured by reciprocal serum creatinine and creatinine clearance levels. In a multiple regression analysis used to predict baseline reciprocal creatinine, the best final model (R2 = 0.48) included male sex (p < .001), hypertension at treatment randomization (p = .001), decreased peripheral blood erythrocytes (p = .001), increased tubulointerstitial score (p = .004), and increased fractional excretion of albumin (p = .025) as independent predictors of decreased kidney function. These associations are similar to those seen in the high-risk subset of patients with IgA nephropathy who develop end-stage renal disease. In the eventual outcome analysis of the clinical trial, we will examine the effects of treatment on the two potentially modifiable risk factors, hypertension and proteinuria, on renal function.
 ...
PMID:Clinical and histopathologic associations with impaired renal function in IgA nephropathy. Mayo Nephrology Collaborative Group. 800 31

ACE inhibitor challenged renal scintigraphic studies offer noninvasive means of evaluating patients for renovascular hypertension, and provide help in selecting patients who will benefit most from interventional procedures designed for alleviation of renal artery stenosis. These studies provide functional assessment of each kidney which also helps the vascular surgeons to plan which renal artery to repair first, when bilateral renal arteries are stenotic, prior to an abdominal aortic aneurysm repair. Vasotec challenged Tc99mMAG3 renal scintigraphy is one of such tests with several advantages over other similar methods, and appears to have a great potential of being a preferred scintigraphic study for evaluation of renovascular hypertension.
 ...
PMID:Scintigraphic evaluation of renovascular hypertension. 812 34

The effects of captopril on the response of cytosolic free Ca2+ concentration in cultured vascular smooth muscle cells of aortas from Wistar-Kyoto and spontaneously hypertensive rats to angiotensin II (Ang II) and bradykinin were studied using fura 2. Incubation with captopril for longer than 10 minutes caused a decreased response of cytosolic free Ca2+ to Ang II and bradykinin. Maximal effects of captopril were observed after a 40-minute incubation. The inhibitory effect of captopril was abolished in Ca(2+)-free medium, suggesting that captopril acts by blocking Ca2+ influx. Similar effects were observed with enalaprilat. Isometric contraction of aortic strips induced by Ang II in normotensive rats was reduced from 6.5 +/- 2.5 to 1.8 +/- 0.6 mN by a 40-minute incubation with 1 mumol/L captopril (P = .016). Enalaprilat similarly decreased the Ang II-induced contraction. Besides the inhibition of the angiotensin converting enzyme, direct effects of Ang II converting enzyme inhibitors on vascular contraction and Ca2+ influx in vascular smooth muscle cells may be of therapeutic relevance.
Hypertension 1993 Dec
PMID:Effect of captopril on vasoconstriction and Ca2+ fluxes in aortic smooth muscle. 824 13

We performed experiments to test the hypothesis that endogenous adenosine acts as an essential cofactor required for eliciting angiotensin II (Ang II)-induced afferent and/or efferent arteriolar vasoconstriction. Enalaprilat (2 mg IV) was administered to anesthetized rats to reduce endogenous Ang II levels. Kidneys and blood were harvested from these animals and used for study of renal microvascular function using the in vitro blood-perfused juxtamedullary nephron technique. Arteriolar inside diameter was monitored videomicroscopically in (1) normal kidneys, (2) kidneys subjected to adenosine receptor blockade (100 mumol/L 1,3-dipropyl-8-p-sulfophenylxanthine), and (3) kidneys continuously exposed to 1 mumol/L adenosine. Under resting conditions, arteriolar diameters were similar in all three groups of kidneys, averaging 24.8 +/- 1.0 microns (n = 23) in afferent arterioles and 24.0 +/- 0.9 microns (n = 16) in efferent arterioles. In normal kidneys, adenosine (10 mumol/L) decreased both afferent (10.2 +/- 2.0%) and efferent (6.5 +/- 0.8%) diameters, an effect that was absent in kidneys subjected to adenosine receptor blockade. Ang II (10 pmol/L to 100 nmol/L) elicited dose-dependent vasoconstriction of both vascular segments in normal kidneys. At a concentration of 100 nmol/L, Ang II decreased afferent diameter by 36.8 +/- 8.5% and efferent diameter by 30.8 +/- 9.6%. Neither afferent nor efferent arteriolar Ang II dose-response relations were significantly different in kidneys treated with low-dose adenosine or the adenosine receptor blocker. These observations refute the hypothesis that a receptor-mediated action of adenosine is required for Ang II-induced constriction of juxtamedullary afferent or efferent arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 Jan
PMID:Renal arteriolar angiotensin responses during varied adenosine receptor activation. 828 42

To study the oxytocic effect of trypsin, we measured the force of isometric contraction in uteri isolated from estrogenized rats exposed to trypsin (8.8 x 10(-10) to 1.7 x 10(-6) mol/L) either alone or in the presence of receptor antagonists to angiotensin II [saralasin ([Sar1,Ala8]angiotensin II) or DuP 753 (losartan)] or to kinins (D-[Arg0,Hyp3,Thi5,8,D-Phe7]-bradykinin). We found that saralasin or DuP 753, but not the kinin antagonist, displaced the dose-response curve to the right. Exposure to exogenous angiotensin I desensitized the preparation to further doses of either angiotensin I or II or trypsin, without altering the effects of oxytocin or bradykinin. Enalaprilat (an angiotensin I converting enzyme inhibitor) or pepstatin A (a renin inhibitor) also displaced the dose-response curve to trypsin to the right, without altering the effects of oxytocin or angiotensin II. Our results indicate that the response to trypsin is mediated by an agent produced from a substrate present in the uterus and acting on the angiotensin II type 1 receptor and are consistent with both renin and angiotensin I converting enzyme being involved in its mechanism of action, thus supporting the notions that the renin-angiotensin system may be important in the late stages of pregnancy and that serine proteases existing in the uterus may contribute to its activation.
Hypertension 1994 Jan
PMID:Oxytocic effect of trypsin on the isolated rat uterus. 828 69

Hypertension is a major risk factor for the development of heart failure. Despite significant progress in our knowledge of the physiopathology of heart failure, the cause for decompensation in patients with left ventricular hypertrophy (LVH) is still obscure. The angiotensin converting enzyme inhibitor enalaprilat has been found to improve electromechanical coupling of heart cells in animal models. To assess the effects of enalaprilat on ventricular electromechanical coupling in humans, we studied the His bundle electrograms and hemodynamics in 22 hypertensive patients with LVH. Patients received either 2.5 mg enalaprilat or saline placebo intravenously in a double-blind protocol. There were no significant changes in heart rate, and atrioventricular and His-Purkinje conduction times. Ventricular activity duration was reduced from 110 +/- 11 msec to 88 +/- 13 msec after enalaprilat administration (P < .01). Enalaprilat decreased peak-systolic and end-diastolic left ventricular pressures, and arterial and pulmonary pressures, as well as pulmonary and systemic vascular resistances. End-systolic wall stress decreased 18% (P < .01), ejection fraction increased 11% (P < .01), and end-diastolic pressure-volume ratio decreased 50% (P < .001) after enalaprilat administration. There were no significant changes in these parameters after saline infusion. It is concluded that enalaprilat reduces ventricular activation duration and improves ventricular performance in hypertensive patients with LVH. Data suggest that enalaprilat significantly improves excitation-contraction coupling in these patients.
 ...
PMID:Effects of enalaprilat on hemodynamics and ventricular activation duration in hypertensive patients with left ventricular hypertrophy: clinical evidence of improved excitation-contraction coupling with angiotensin converting enzyme inhibition in human hypertension. 839 97

As interactions between the renin-angiotensin and sympathetic nervous systems have been suggested in the pathogenesis of hypertension, we wanted to investigate the effect of chronic renin-angiotensin blockade with losartan and enalaprilat on the sympathetic reactivity to hypotension and on the cardiac beta-adrenergic-coupled adenylyl cyclase pathway in 12-week-old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Both treatments, exerting equipotent shifts of angiotensin-pressure responses, lowered blood pressure and attenuated cardiac hypertrophy similarly in SHR. The nitroprusside-induced hypotension was similar in both strains, but the associated increases in plasma catecholamines and heart rate were higher in SHR. In SHR treated with losartan and enalaprilat, the nitroprusside-induced hypotension was greater and associated with markedly attenuated increases in norepinephrine and heart rate. The binding affinity of cardiac beta-adrenoceptors was significantly lower, and beta2-adrenoceptor subtype was dominant in untreated SHR in contrast to WKY, in which beta1-adrenoceptor subtype was dominant. Enalaprilat treatment increased total beta-adrenoceptor density, whereas both treatments restored the binding affinity and beta1- and beta2-adrenoceptor proportions to normal in SHR. Isoproterenol-, guanylylimidodiphosphate [Gpp(NH)p]-, and forskolin-stimulated adenylyl cyclase reactivity was increased in SHR. Enalaprilat restored adenylyl cyclase reactivity to normal in SHR and reduced the sensitivity (EC50) of Gpp(NH)p-induced cAMP formation in both strains. The present study supports the possibility that functional alterations of the renin-angiotensin and sympathetic systems are involved in hypertension in SHR. The antihypertensive action of losartan and enalaprilat in SHR may be partly mediated through the normalization of sympathetic hyperreactivity and the restoration of beta-adrenergic signaling pathway sensitivity.
Hypertension 1997 Aug
PMID:Effects of renin-angiotensin blockade on sympathetic reactivity and beta-adrenergic pathway in the spontaneously hypertensive rat. 926 Sep 93


<< Previous 1 2 3 4 Next >>