Captopril reduces aortic and microvascular growth in hypertensive and normotensive rats.

Abstract

This experiment was designed to investigate the effect of converting enzyme inhibition on functional and structural vascular alterations in one-kidney, one clip hypertensive rats and in normotensive rats. Starting 1 day before surgery, 100 mg/kg/day captopril was given chronically to half of the hypertensive and normotensive groups in their drinking water. With use of intravital microscopy in the cremaster muscle, arteriolar dimensions were measured 4 weeks later, both before and after topical application of 10~3 M adenosine. Mean blood pressure was 124 ±4 mm Hg in control rats and 103 ±5 mm Hg in captopril-treated control rats (p<0.05). Mean blood pressure was significantly elevated to 183±5 mm Hg in captopril-treated one-kidney, one clip hypertensive rats and 193 ±5 mm Hg in one-kidney, one clip hypertensive rats. With use of histological techniques, a marked reduction of medial-intimal area of the abdominal aorta was found in captopril-treated control rats (24%), and hypertrophy of the aortic wall in one-kidney, one clip hypertensive rats was decreased 26% by captopril. Structural diameter reductions occurred in large arterioles of the captopril-treated control and hypertensive groups and the nontreated hypertensive group. In spite of a significant increase in wall-to-lumen ratio of first-order arterioles in all captopril-treated rats, captopril decreased cross-sectional wall area of these vessels 37% in hypertensive and 20% in control rats, respectively. Measured by stereological techniques, small arteriolar density decreased 30% in captopril-treated hypertensive rats and 17% in captopril-treated control rats. Therefore, smaller arteriolar lumens, decreased aortic and arteriolar cross-sectional wall area, and arteriolar rarefaction after converting enzyme inhibition, in spite of rising or falling blood pressure, are evidence that vascular growth was inhibited in vivo. {Hypertension 1990;15:68-77) T he influence of angiotensin II (Ang II) on vascular structure has been widely studied. Ang II has been shown to stimulate DNA and protein synthesis in cardiovascular tissue 1 and induce hypertrophy without cellular proliferation in cultured rat aortic smooth muscle cells (SMCs) maintained in a defined serum-free medium.2 Ang II also increased growth rates and cell size in cultured human SMCs grown in the presence of serum. However, all of these were in vitro studies. In vivo, captopril not only lowered blood pressure, but was more effective than hydralazine and propranolol in preventing increases in aortic SMC content, medial SMC weight, and percentage of polyploid SMCs in spontaneously hypertensive rats (SHR).4 SMC volume was also reduced in captopril-treated SHR and Wistar-Kyoto (WKY) rats. 4 In mesenteric arteries, captopril induced a long-lasting decrease in wallto-lumen (W/L) ratio in SHR and simultaneously induced long-lasting decreases in myocardial and aortic wall hypertrophy that persisted up to 7 weeks after treatment withdrawal.5 Recently, converting enzyme inhibition in two-kidney, one clip hypertensiv...

Effects of a beta-blocker or a converting enzyme inhibitor on resistance arteries in essential hypertension.

“…It could be the equivalent at the level of these subcutaneous small arteries from hypertensive patients of findings in renin-dependent two-kidney, one clip Goldblatt hypertensive rats, in which another converting enzyme inhibitor, captopril, produced an increase in the rarefaction of muscular arterioles, an atrophic response probably resulting from the disappearance of the trophic effect of angiotensin II under the effects of converting enzyme inhibition. 40 Treatment with cilazapril resulted in a correction to normal of wall tension development of these small subcutaneous arteries in response to endothelin-1. The mechanism underlying this effect is unclear.…”

“…In contrast, the /}-blocker atenolol does not significantly affect the alterations in resistance blood vessel structure and function. Whether this "reverse remodeling" 40 translates into improvement in outcome of hypertensive patients treated with cilazapril or other converting enzyme inhibitors remains to be determined.…”

Tissue Inhibition of Angiotensin-Converting Enzyme Activity Stimulates Angiogenesis In Vivo

“…Ang II has been shown to augment microvessel density in rat cremaster muscle 7 and promote angiogenesis of precapillary and postcapillary vessels in the chorioallantoic membrane of the chick embryo. 8 Although administration of captopril was shown to block neovascularization in the rat cornea 9 and microvascular development in hypertensive and normotensive rats, 10 other ACE inhibitors have been reported to increase capillary density in rat limb muscle, 11 sciatic nerve, 12 and coronary microvasculature. [13][14][15] The present study was carried out to evaluate the effects of ACE inhibition on neovascularization of ischemic tissue in vivo.…”

Angiotensin II causes vascular hypertrophy in part by a non-pressor mechanism.

“…]thymide uptake into vessel DNA is increased before arterial pressure rises. 32 4) Angiotensin converting enzyme inhibition in the SHR 53 and in the renal hypertensive rat 54 has an effect on vascular structure greater than can be explained by the fall of arterial pressure. That decreased Ang II is important in the hypotensive and structural effects under these circumstances is suggested by the observation 55 that subcutaneous infusion of the peptide (in the dose used here) in SHR treated with angiotensin converting enzyme inhibitor restores both pressure and structure to values seen in the untreated control SHR.…”