Coronary microvasculature alteration in hypertensive rats. Effect of treatment with a diuretic and an ACE inhibitor

The development of hypertension is accompanied by rarefaction of arterioles and capillaries in both animal models and humans. Although many studies ha ve examined the effects of antihypertensive therapies on hemodynamics, card iac hypertrophy, and large vessel structure, the question of whether change s in microvascular density induced by hypertension can be restored by pharm acologic treatment has yet to be answered. We report a series of experiments performed in rats with renovascular hyper tension induced by unilateral nephrectomy and renal artery stenosis (Goldbl att one-kidney, one-clip model). Animals were treated for 4 weeks, after re nal artery clipping, either with an angiotensin converting enzyme inhibitor (perindopril [PER], 0.76 mg/kg/day), or with an indol derivative diuretic with specific vascular properties (indapamide [IDP], 0.24 mg/kg/day) or wit h the combination of both drugs at the same doses as during monotherapy. Co ronary microvessel densities (arterioles and capillaries) were evaluated by double immunolabeling in nonserial cryostat sections of the left ventricul ar inner myocardium. After 4 weeks of hypertension (mean arterial pressure. 174 +/- 11 v 124 +/- 5 mm Hg in normotensive (NT) controls. P < .01), cardiac hypertrophy (+59% , P < .001) was associated with a significant increase in myocardial arteri olar density (+27%, P < .01), and a decrease in capillary density (-12%, P < .05). Treatment with PER prevented the increase in arterial pressure, heart weigh t, and arteriolar density, but did not significantly affect the low coronar y capillary density in comparison with that measured in untreated hypertens ive (HT) rats. Treatment with IDP preserved normal capillary myocardial density but did no t significantly lower the blood pressure (BP) (169 +/- 9 mm HE) and only sl ightly reduced the cardiac ventricular hypertrophy: -14% v untreated HT (P < .05) and +37% v NT (P < .01). In the same way, IDP normalized the left ve ntricular capillary density in spontaneously HT rats (+18% v untreated rats , P < .01). The combination of both drugs, PER and IDP, at the same low doses as during monotherapy, resulted in normal levels of arterial pressure and complete n ormalization of cardiac hypertrophy and arteriolar and capillary myocardial densities. In conclusion, the results observed after PER suggest that blockade of the renin-angiotensin system could inhibit large coronary vessel growth but min imally affects the capillary density despite complete normalization of BP. Indapamide could have beneficial effect on myocardial capillary density. Th e combination of IDP and PER has additional effects and prevents the increa se in BP and cardiac weight, and reverses microvascular rarefaction, specif ically arteriolar and capillary densities. (C) 2001 American Journal of Hyp ertension, Ltd.