Abstract
Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto control rats (WKY) were treated for 14 weeks with a novel calcium channel blocker, mibefradil (Ro40-5967), or an angiotensin-converting enzyme inhibitor, cilazapril. Blood pressure was significantly reduced by treatment in SHRs from > 200 mm Hg to 155 +/- 2 mm Hg by mibefradil and to 138 +/- 1 mm Hg by cilazapril (p < 0.01). Cardiac hypertrophy was significantly reduced by treatment but to a greater degree with cilazapril than with mibefradil. Conduit and large arteries also had significant regression of hypertrophy. Small arteries (luminal diameter, 200-300 microns) of the coronary, renal, mesenteric, and femoral circulations exhibited significant hypertrophy and remodeling in SHRs in comparison to WKYs. Cilazapril treatment resulted in increased lumen, reduced media thickness, and media-to-lumen ratio in all four vascular beds. Mibefradil treatment induced regression of luminal diameter to a significant degree only in the mesenteric and femoral small arteries but decreased media thickness and media to lumen diameter in all four vascular beds. The greater extent of regression of cardiac and vascular hypertrophy and remodeling with cilazapril than with mibefradil may relate to the degree of blood pressure reduction, which, with the doses used, was larger with the angiotensin-converting enzyme inhibitor than with the calcium channel blocker. In WKY rats, treatment had no effect except with cilazapril on lumen diameter of small arteries and with mibefradil on heart weight, both of which increased. These results demonstrate the blood-pressure dependence of regression of cardiovascular hypertrophy and remodeling and the possibility of achieving "reverse remodeling" of large and small arteries with converting enzyme inhibition or calcium channel blockade in SHRs, as well as the near absence of effects of these agents on cardiovascular characteristics in WKYs.
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