Effects of Chronic Treatment with SQ29852 on Spontaneous Smooth Muscle Tone and Endothelium-Dependent Relaxation in Aorta of Stroke-Prone Spontaneously Hypertensive Rats

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Abstract
The effects of chronic treatment with SQ29852, an angiotensin-converting enzyme inhibitor, on spontaneous smooth muscle tone and endothelium-dependent relaxation of aorta from stroke-prone spontaneously hypertensive rats (SHRSP) were studied and compared with those of captopril. Endothelium-removed aorta from 16-week-old SHRSP exhibited a high amplitude of spontaneously developed active tension (active tone), whereas no active tone was observed in the preparation from control normotensive Wistar-Kyoto (WKY) rats. Treatment with SQ29852 or captopril at age 5–16 weeks prevented the development of hypertension. No active tone could be detected in the preparation from SQ29852-treated SHRSP. Endothelium-dependent relaxation was markedly reduced in the preparation from non-treated SHRSP compared with WKY rats. Treatment with SQ29852 prevented the impairment of endothelium-dependent relaxation. It was also shown that norepinephrine-induced contraction was markedly depressed in en-dothelium-intact aorta from SQ29852-treated rats. The effects of SQ29852 were more prominent than those of hydralazine when blood pressure was maintained at similar levels. It was suggested that SQ29852 exerts an action on both vascular smooth muscle and endothelium that is mediated by the inhibition of angiotension-converting enzyme in addition to indirect actions of SQ29852 that are brought about by blood pressure lowering.

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