Hydrochlorothiazide abolishes the anti‐atherosclerotic effect of quinapril

Abstract

1. Antihypertensive treatment has been demonstrated to result in persistent reductions in morbidity and mortality due to stroke. However, the coronary risk attributable to hypertension has been only partially reversed. We hypothesized that diuretics could have unfavourable effects on atherosclerosis. 2. New Zealand rabbits were fed a 0.5% cholesterol-enriched diet for 12 weeks, followed by a 0.1% cholesterol diet for another 12 weeks. During the last 12 week period, 40 animals were randomly assigned to one of four groups: (i) group I was the control group; (ii) group II received hydrochlorothiazide (10 mg/day); (iii) group III received quinapril (30 mg/day); and (iv) group IV was treated with hydrochlorothiazide (10 mg/day) plus quinapril (30 mg/day). 3. The treatments did not affect either the lipid profile or serum electrolytes and oxidative stress. However, endothelium-dependent vasorelaxation in isolated aortic rings was significantly improved with quinapril (group III) treatment (P < 0.001 vs other groups). In addition, therapy with quinapril promoted a significant reduction in atherosclerosis (intima area, intima/media ratio and perimeter of vessel with plaque; P < 0.05 vs other groups), as well as in cholesterol content of the aorta (P < 0.05 vs groups II and IV). 4. In conclusion, hydrochlorothiazide did not modify atherosclerosis and, when added to quinapril treatment, impaired the anti-atherosclerotic effect seen with quinapril alone.

Irbesartan for the treatment of hypertension in patients with the metabolic syndrome: A sub analysis of the Treat to Target post authorization survey. Prospective observational, two armed study in 14,200 patients

“…In contrast, ARBs have been shown to have beneficial effects on multiple components of the metabolic syndrome [29], an observation consistent with primary links between angiotensin II and insulin resistance [30]. Similarly HCTZ has been reported to abolish the antiatherosclerotic effects exerted by inhibition of the renin-angiotensin system with quinapril, at least in hypercholesterolemic rabbit models [31]. Given the high proportion of patients difficult to control with monotherapy and the value of diuretics in a variety of patient populations, it is of particular importance to counterbalance the untoward effects by using low dose combination therapy with an ARB.…”

Valsartan, Blood Pressure Reduction, and C-Reactive Protein

“…33 Similarly, HCTZ has been reported to reduce the antiatherosclerotic effects ascribed to inhibition of the renin-angiotensin system, at least in hypercholesterolemic rabbit models. 34 Whether or not HCTZ alone adversely impacts on vascular inflammation will need evaluation in future clinical trials.…”

Euterpe Oleracea (Açai) Modifies Sterol Metabolism and Attenuates Experimentally-Induced Atherosclerosis

“…We previously demonstrated improved endothelial function by statins 25) and by angiotensin converting-enzyme inhibitor 26) , accompanied by attenuation of atherosclerosis development in rabbits, independent of changes in serum cholesterol levels.…”