Impairment of Endothelium-dependent Relaxation and Changes in Levels of cyclic GMP in Carotid Arteries from Stroke-prone Spontaneously Hypertensive Rats

Author:

Miyata Noriyuki1,Tsuchida Katsuharu1,Tanaka Makoto1,Otomo Susumu1

Affiliation:

1. Research Center, Taisho Pharmaceutical Co. Ltd, 1–403 Yoshino-cho, Ohmiya, Saitama 330, Japan

Abstract

Abstract Endothelium-dependent relaxation of carotid arteries and changes in levels of cyclic (c)GMP between stroke-prone spontaneously hypertensive (SHRSP) and Wistar-Kyoto (WKY) rats have been compared. The concentration-response curve for acetylcholine (ACh)-induced relaxation was shifted to the right in carotid arteries from SHRSP. Relaxation responses produced by calcimycin (A 23187) and melittin, both endothelium-dependent agents, were depressed in carotid arteries from SHRSP. Relaxation responses produced by sodium nitroprusside and 8-Br-cGMP were similar to those in strips from WKY. ACh-induced production of cGMP was significantly decreased in carotid arteries from SHRSP when compared with the level for similarly treated strips from WKY. These results suggest that functional changes in endothelium, but not guanylate cyclase activity or cGMP sensitivity in the carotid arteries, may occur in hypertension. Thus, impaired endothelium-dependent relaxation in SHRSP may play an important role in hypertensive vascular diseases such as stroke.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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