Assessment of the acute arterial effects of converting enzyme inhibition in essential hypertension: a double-blind, comparative and crossover study (original) (raw)
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Journal of Human Hypertension, 2000
Objective: Angiotensin-converting enzyme (ACE) inhibitors have beneficial effects on arterial compliance and distensibility and favourably modify the arterial pressure waveform in hypertensive patients. The objective of our study was to explore the possible effects of adding an ATII AT 1 receptor antagonist to an ACE inhibitor on augmentation pressure, a measure of arterial stiffness, and pulse pressure amplification in patients with poorly controlled essential hypertension. Design and methods: We studied a group of 18 patients with poorly controlled hypertension, despite at least three antihypertensive drugs including an ACE inhibitor, before, at 2 h and 2 weeks following the administration of 80 mg of valsartan, an ATII AT 1 receptor antagonist. Haemodynamic responses were measured by cuff sphygmomanometry, arterial pulse-wave analysis and the pulse pressure gradient was calculated as the difference between the brachial pulse pressure (cuff sphygmomanometry) and derived aortic pulse pressure (arterial pulse wave analysis). Results: Blood pressure decreased significantly (P Ͻ 0.001) and the effect was more pronounced on central
Hypertension Research, 2000
Angiotensin-converting enzyme inhibitors (ACEIs) may have different effects on cardiac hypertrophy than on vascular hypertrophy. Arginine vasopressin (AVP) may promote cardiac hypertrophy. Our aims were (1) to simultaneously examine the chronic effects of ACEIs on hypertrophy of the heart and hypertrophy of the coronary and renal interlobular arteries, and (2) to clarify the relation between AVP concentration (AVPC) and cardiac hypertrophy. ACEI (delapril: 30 mg/kg/day) or vehicle (5% arabic gum) was administered in a preventive (4 to 28 weeks of age) or a therapeutic (12-24 weeks of age) protocol in spontaneously hypertensive rats. In both protocols, delapril produced a slight but significant decrease in systolic blood pressure. In the therapeutic protocol, the weight of the left ventricle (mean±SE) was lower (p<0.05) in the ACEI group (64±2 mg/100 g body weight) than in the control group (69±1 mg/100 g body weight). Plasma renin activity was significantly higher in the ACEI group than in the control group in both the preventive (p <0.01) and therapeutic (p<0.01) protocols. In the therapeutic protocol, AVPC was significantly (p<0.05) lower in the ACEI group than in the control group. AVPC was significantly (p=0.02, r=0.46) correlated with the weight of the left ventricle in the therapeutic protocol. For both protocols, no differences were noted between the ACEI and control groups in the vascular hypertrophy of the coronary and renal interlobular arteries. We conclude that (1) the preventive or therapeutic effect of ACEIs on hypertrophy may not be the same in the heart as in the coronary and renal arteries; and (2) AVP was significantly correlated with the left ventricular weight. This indicates that AVP could play a role in the etiology of cardiac hyper
Hypertension, 1984
The antihypertensive, hemodynamic, and humoral effects of the new convertingenzyme inhibitor enalapril (MK-421) were assessed by sequential studies during 3 months of uninterrupted treatment (20 mg twice daily) in 10 hypertensive patients. Six achieved good blood pressure (mean arterial pressure) control with enalapril alone (from 126 ± 7.0 mm Hg pretreatment to 105 ± 1.6 mm Hg at 3 months, p < 0.05). The other four required the addition of diuretics (hydrochlorothiazide 25 mg orally twice daily) at different stages of follow-up, with resultant blood pressure control (128 ± 9.6 mm Hg pretreatment to 113 ± 1.9 mm Hg at 2 months after the addition of diuretics). Neither the acute nor long-term blood pressure response could be predicted from the pretreatment levels of plasma renin activity. The blood pressure reduction during enalapril therapy was characterized by a decrease in total peripheral resistance (53 ± 2.5 U-M 2 pretreatment to 38 ± 3.0 U-M 2 at 3 months, p < 0.05) with no significant change in cardiac output or heart rate. This lack of reflex tachycardia could not be ascribed to baroceptor dysfunction since the response to head-up tilt (the increase in diastolic blood pressure, in heart rate, and in plasma catecholamines) was normal and not significantly different from pretreatment response. Average blood volume did not change (91% ± 4.3% of normal in the pretreatment period to 93% ± 2.9% after 3 months of therapy, p = NS) despite the significant lowering of arterial pressure with enalapril alone (n = 6). This could have been possibly related to the reduction in plasma aldosterone (12.6 ± 2.3 to 8 ± 0.9 ng/dl, p < 9.95) induced by treatment. In conclusion, the hemodynamic consequences of blood pressure reduction by enalapril were similar to those produced by other converting-enzyme inhibitors and angiotensin II antagonists. These findings suggest that the hemodynamic effects of enalapril were related to interference with the generation of angiotensin II rather than a direct action of the drug.
American journal of …, 2007
We measured the effects of angiotensin II blockade on arterial stiffness, augmentation index (AI%), pulse wave velocity (PWV), and blood pressure (BP) in 12 hypertensive patients (mean 49 Ϯ 11 years) in a 4-week, randomized, cross-over study comparing valsartan 160 mg/day with captopril 100 mg/day, with a 2-week washout period. Subsequently both therapies were combined. Reductions in PWV and AI% remained significant when corrected for BP. Combined therapy reduced PWV and AI% (P Ͻ .05) more than monotherapy, even when corrected for BP. The study shows that angiotensin receptor antagonists reduce arterial stiffness in hypertension comparable with and possibly additive to angiotensin converting enzyme inhibition. Am J Hypertens 2002;15:321-325
Essential hypertension: effect of an oral inhibitor of angiotensin-converting enzyme
British Medical Journal, 1979
and conclusions Captopril, a specific oral inhibitor of angiotensinconverting enzyme, was given to 18 unselected patients with moderate essential hypertension. Mean blood pressure fell by 14.5% at the maximum dose given, and this fall was significantly correlated with the initial plasma renin activity. The main fall in blood pressure occurred two hours after the first dose of captopril. These results suggest that captopril effectively lowers blood pressure in patients with essential hypertension and that the renin-angiotensin aldosterone system may
Hypertension, 2005
Some evidence suggests that long-term angiotensin-converting enzyme (ACE) inhibition may become less effective, thereby increasing angiotensin II levels, which could be inhibited by the addition of an angiotensin receptor blocker. We conducted a meta-analysis of randomized trials with searches of MEDLINE, EMBASE, and Cochrane databases. Overall, the combination of an ACE inhibitor and an angiotensin receptor blocker reduced ambulatory blood pressure by 4.7/3.0 mm Hg (95% confidence interval [CI], 2.9 to 6.5/1.6 to 4.3) compared with ACE inhibitor monotherapy and 3.8/2.9 mm Hg (2.4 to 5.3/0.4 to 5.4) compared with angiotensin receptor blocker monotherapy. Clinic blood pressure was reduced by 3.8/2.7 mm Hg (0.9 to 6.7/0.8 to 4.6) and 3.7/2.3 mm Hg (0.4 to 6.9/0.2 to 4.4) compared with ACE inhibitor and angiotensin receptor blocker, respectively. However, the majority of these studies used submaximal doses or once-daily dosing of shorter-acting ACE inhibitors and, when a larger dose of shorter-acting ACE inhibitor was given or a longer-acting ACE inhibitor was used, there was generally no additive effect of the angiotensin receptor blocker on blood pressure. Proteinuria was reduced by the combination compared with ACE inhibitor and angiotensin receptor blocker monotherapy, an effect that was independent of blood pressure in several studies, suggesting that the combination could have benefits in proteinuric nephropathies. None of the studies was of sufficient size and duration to determine whether there may be safety concerns. In conclusion, although there is a small additive effect on blood pressure with an ACE inhibitor-angiotensin receptor blocker combination, the routine use of this combination in uncomplicated hypertension is not recommended until more carefully controlled studies are performed. (Hypertension. 2005;45:880-886.)
Haemodynamic effects of enalapril, a new converting enzyme inhibitor, in hypertensive patients
European Journal of Clinical Pharmacology, 1985
The haemodynamic effects of enalapril (EN), a new, long-acting, nonsulphhydryl converting enzyme inhibitor, were evaluated by non-invasive methods in 10 adult patients with mild to moderate essential hypertension (EH). Patients were randomly assigned, double blind to 2 treatment groups (EN 20 mg o.d. or 10 mg b.d.) for 4 weeks, and were crossed over to the other dosage regimen after a 2-week washout period. Measurements included mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), limb blood flow (LBF), plasma aldosterone (ALD), plasma renin activity (PRA) and systolic time intervals (STI). Both regimens (b.d. and o.d.) significantly reduced MAP (15.3% and 16.3%, respectively), total peripheral resistance (20.3% and 21.8%, respectively), limb vascular resistance (24.1% and 24.9%) and ALD (33.5% and 36.9%) and increased CO (7.8% and 8.7%), LBF (10.9% and 11.6%) and PRA (10.4% and 9.5%). No significant change was observed in HR or STI. EN 20 mg o.d. or 10 mg b.d. reduced arterial pressure to a similar extent through a fall in total peripheral resistance. An increase in CO was also observed.
American heart journal, 2004
The renin-angiotensin-aldosterone system has a pivotal role in the short- and long-term regulation of blood pressure through its principal mediator, angiotensin II. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II-receptor blockers (ARBs) decrease the deleterious effects of angiotensin II on the vasculature and heart, but have different mechanisms of action. Although the blood pressure-lowering effect of ACE inhibitors and ARBs is equivalent to that of most other antihypertensive agents, emerging data suggest that these drug classes may have a greater effect on decreasing cardiovascular morbidity and mortality rates in specific patient populations. We reviewed large (approximately > or =5000 patients) hypertension clinical trials using ACE inhibitors and ARBs and with cardiovascular morbidity/mortality end points. Six trials of ACE inhibitors and 5 trials of ARBs (3 completed, 2 ongoing) were selected for this analysis. Data from these hypertension mega-trials su...
2003
Abundant evidence showed that angiotensin-converting enzyme (ACE)-inhibitors reduce longterm cardiovascular morbidity and mortality rates in patients with heart failure and myocardial infarction. More recent studies revealed clinical benefits also in hypertensive patients with comorbidity and lead to an extension of clinical indications. Indeed in patients with severe hypertension differences between drugs are hardly detectable because the risk reduction is mainly related to the control of blood pressure values independent of the type of therapy. Conversely in the presence of comorbid conditions, especially in diabetics, the association of ACE-inhibitors with antihypertensive treatments proved its efficacy in reducing cardiovascular morbidity and mortality so that the role of mechanisms extending beyond blood pressure reduction can be postulated.