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

Cocaine abuse can cause cardiovascular damage leading to hypertension, myocardial ischaemia and infarction. This might be partly due to the effects of cocaine on the microcirculation about which little is known, although its effects on the macrovessels are well documented. Accordingly, we used in vivo videomicroscopy to study the vasoconstrictive effect of cocaine on arterioles of different diameter. They were classified into three orders (A2, A3, A4) according to their position in the microvascular network and their diameter. Since calcium antagonists have been reported to exert a protective effect against the cardiovascular disorders induced by cocaine, we tested the hypothesis that this protective action occurs in the microcirculation. We found that intra-arterial administration of the calcium antagonist Nitrendipine greatly inhibited the vasoconstriction induced by cocaine in all three arteriole orders. The degree of inhibition ranged from 44 to 56%. Combined administration of benzodiazepine and an angiotensin converting enzyme inhibitor has also been reported to protect rats against cocaine-induced hypertension and to increase survival rates after a toxic dose of cocaine. Since the mechanisms of this protection are not yet clear, we also studied the effect of the angiotensin converting enzyme inhibitor Enalaprilat on cocaine-induced vasoconstriction. Intra-arterial administration of Enalaprilat inhibited this vasoconstriction slightly but significantly in arteriole orders 2 and 3 by 27 and 24% respectively, but not in order 4. We concluded that Nitrendipine is a powerful inhibitor of cocaine-induced vasoconstriction in the microcirculation. The small but significant inhibition found with Enalaprilat for the larger arterioles suggests that the local angiotensin II level may affect the response to cocaine. However, since the Enalaprilat-induced inhibition was very limited, we conclude that mechanisms other than those occurring in the peripheral microcirculation account for the protection afforded by Enalaprilat against the harmful effects of cocaine.
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PMID:Microvascular effects of cocaine; interaction with nitrendipine and enalaprilat. 164 95

ACE-inhibitors have for some time been used in the treatment of hypertension. Apart from inhibiting the conversion of angiotensin I to II, the drugs also affect the metabolism of some inflammatory agents, like bradykinin and substance P. Egg albumin (EA)-sensitized guinea pigs were pretreated with the ACE-inhibitors. Measurement of flare and wheal areas induced by an intradermal injection of EA, showed that enalaprilat significantly increased, whereas cilazaprilat slightly decreased, the reaction area. Enalaprilat also showed an enhancement in histamine and substance P (SP) contents in the skin. In vitro incubation of guinea pig biopsies with enalaprilat potentiated EA- but not SP-induced histamine release. The EA-induced effect was abolished if the animals were pretreated with capsaicin. The conclusion is that cilazaprilat, in contrast to enalaprilat, does not potentiate inflammatory reactions in the guinea pig.
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PMID:Enalaprilat versus cilazaprilat: a comparison of allergic skin reactions in the guinea pig. 171 46

The effect of rapid converting enzyme inhibition (CEI) with intravenous enalaprilat on technetium-99m-(99mTc) diethylenetriaminepentaacetic acid (DTPA) and 99mTc-dimercaptosuccinic acid (DMSA) renograms was evaluated in rats with two-kidney, one-clip renovascular hypertension. Rapid sequential DTPA renograms, performed immediately before and five minutes after enalaprilat injection (30 micrograms/kg), demonstrated a selective decrease in clipped kidney DTPA plasma clearance following CEI and no significant effect on unclipped kidney function. Pre- and post-CEI data were obtained with a single injection of DMSA by administering enalaprilat five minutes after the radiopharmaceutical. Enalaprilat slowed the rate of DMSA accumulation in clipped relative to unclipped kidneys, and reduced the clipped/unclipped kidney ratio of absolute DMSA uptake at 10 and 30 min. DTPA and DMSA were equally effective in demonstrating the CEI effect. Enalaprilat was also compared with captopril (3 mg/kg, intraperitoneally), using sequential DTPA renograms. Clipped kidney DTPA plasma clearance was reduced to an identical degree (40%) by both converting enzyme inhibitors. Clinical renographic protocols can probably be devised to take advantage of the rapid, reliable CEI of enalaprilat, thereby shortening total procedure time.
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PMID:Enalaprilat-enhanced renography in a rat model of renovascular hypertension. 215 32

This study was designed to identify the possible role of vasoconstricting compounds released from ischemic tissues in the hemodynamic response to cross-clamping of the thoracic aorta. Twenty-one dogs were anesthetized with pentobarbital sodium. The left hindlimb was denervated, vascularly isolated, and pump perfused at a constant rate with blood drained from the inferior vena cava after passing through a gas-exchanging membrane where oxygen and carbon dioxide tensions were maintained within normal limits. Left and right thoracotomies were performed, and the aorta and inferior vena cava were cross-clamped. The cross-clamping was associated with 33-45% increase in limb vascular resistance in denervated control animals (n = 6). In animals pretreated with Enalaprilat (2 mg/kg, n = 6), an angiotensin-converting enzyme inhibitor, limb vascular resistance did not change significantly. In animals pretreated with phenoxybenzamine (3 mg/kg, n = 6), an alpha-adrenoceptor antagonist, limb vascular resistance significantly decreased to 43% of preclamped level. The study demonstrated that vasoconstrictive compounds, such as angiotensin and catecholamines, play a role in systemic hemodynamic changes, including arterial hypertension, observed during cross-clamping of the thoracic aorta.
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PMID:Angiotensin and alpha-adrenoceptor activation play a role in hemodynamic response to aortic cross-clamping. 216 66

The orally active angiotensin-converting inhibitors (ACE inhibitors) such as captopril and enalapril represent a significant therapeutic advance in the treatment of hypertension and congestive heart failure. Enalapril differs from captopril in several respects. It is a prodrug converted by hepatic esterolysis to the active (but more poorly absorbed) diacid, enalaprilat. Enalaprilat is more potent than captopril, more slowly eliminated and does not possess a sulfhydryl (SH) group. Enalapril was rapidly followed by a number of newer ACE inhibitors, the majority of which are similar to enalapril in that they are prodrugs, converted by hepatic esterolysis to a major active but poorly absorbed diacid metabolite. In one case (delapril) there are 2 active metabolites; in another (alacepril) the prodrug is converted in vivo to captopril. Lisinopril is an exception in that it is an enalaprilat-like diacid but with acceptable oral bioavailability, so that the prodrug route is not employed. The newer ACE inhibitors are at widely different stages of development, and it is not yet clear how many will reach regular clinical use. Of these newer drugs, lisinopril is the longest established and is the subject of the widest published literature. For a number there is as yet little published pharmacokinetic information. A variety of assay methods have been employed to characterise the pharmacokinetics of the ACE inhibitors, including enzymatic techniques, radioimmunoassay and chromatography. The peak plasma concentrations of the prodrugs are generally observed at around 1 hour and those of the diacid metabolites at about 2 to 4 hours. However, there is considerable variation within and between drugs, with benazepril and benazeprilat reaching peak concentrations early and enalapril and enalaprilat typical of later times to peak. Absorption of the active diacids is generally poor, and moderate (typically 30 to 70%) for the prodrugs. The bioavailability of lisinopril is about 25%. It is difficult to talk meaningfully about half-lives of the active drugs. The declines in their plasma concentrations are polyphasic and, if analytical sensitivity allows, active drug may be found at 48 hours or more following administration. This may reflect binding to ACE in plasma. Half-lives of accumulation are of the order of 12 hours; protein binding varies from little (lisinopril) to 90% (benazeprilat). Elimination is mostly renal but there may be biliary elimination for some, such as benazeprilat and fosinopril. The half-lives of the prodrugs are short. Impaired renal function decreases the elimination rate of the diacids.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of the newer ACE inhibitors. A review. 220 79

The hemodynamic effects of enalaprilat (MK-422) and lisinopril (MK-521) were compared with the calcium channel blocker felodipine in dogs with ischemic left ventricular (LV) failure. The combination of nitrendipine plus enalapril was also examined in ischemic failure and in rats with spontaneous hypertension. In anesthetized dogs coronary embolization with 50 micron plastic microspheres reduced cardiac output and LV dP/dt max by approximately 40%, and LV end-diastolic pressure increased to greater than 13 mm Hg. Enalaprilat and lisinopril reduced mean arterial pressure by a maximum of 20 mm Hg and total peripheral resistance by approximately 30%. Left ventricular dP/dt:LVP, which was substantially decreased by embolization, was slightly increased by both angiotensin converting enzyme (ACE) inhibitors. The calcium entry blockers felodipine and nitrendipine qualitatively produced many of the same hemodynamic effects as the ACE inhibitors, but, in addition, they markedly reduced coronary resistance, increased myocardial blood flow, and did not alter cardiac contractility (LV dP/dt max). In spontaneously hypertensive rats single doses of nitrendipine (1.25 to 5.0 mg/kg per os) and enalapril (0.3 and 3.0 mg/kg per os) reduced mean arterial pressure, but differences were observed in the onset (enalapril 2 h versus nitrendipine 0.5 h), the duration of action, and magnitude of effect. In terms of blood pressure lowering, nitrendipine, 5.0 mg/kg per os, was clearly additive to 3.0 mg/kg per os of enalapril, but other combinations (enalapril, 3 mg/kg per os plus 0.625 mg/kg of nitrendipine or enalapril, 0.3 mg/kg per os plus 0.625 mg/kg nitrendipine) were not.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enalapril in experimental hypertension and acute heart failure: comparison with calcium channel blockers. 242 87

To assess the vascular involvement of renin-angiotensin system inhibition in human hypertension, acute effects of intravenous enalaprilat on brachial artery diameter, blood flow, and blood velocity were investigated in hypertensive patients by pulsed Doppler technique and compared with effects of saline vehicle. Compared with saline vehicle, enalaprilat reduced blood pressure (P less than 0.001) and increased brachial arterial diameter (P less than 0.01) and brachial blood flow (P less than 0.01). Enalaprilat effect on arterial pulse pressure was dependent on preinjection pulse pressure (r = -0.76; P less than 0.001), but its effect on mean blood pressure was not dependent on preinjection mean blood pressure. On the other hand, enalaprilat effect on arterial blood flow was negatively correlated with preinjection blood pressure (r = -0.64; P less than 0.02). The findings point to different responses of large and small arteries to intravenous enalaprilat.
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PMID:Brachial artery hemodynamic response to acute converting enzyme inhibition by enalaprilat in essential hypertension. 282 67

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)
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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.
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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.
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PMID:Enalaprilat in hypertensive emergencies. 300 76


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