신혈관성 고혈압쥐에서 Atrial Natriuretic Peptide가 혈관 기초장력에 미치는 영향

Abstract

Hypertension may be involved an alteration of intrinsic basal tone in vascular smooth muscle. The purpose of this study was to investigate the vasorelaxant effect of atrial natriuretic peptide (ANP) on isolated non-contracted aorta from two-kidney, one clip (2K1C) renovascular hypertensive rats. 2K1C hypertension was induced by clipping the left renal artery and were used 6 weeks later. Age-matched rats receiving a sham treatment, which served as controls. The thoracic aortae were mounted in tissue baths to measure the isometric tension. ANP diminished basal tone in previously unstimulated thoracic aortic rings from 2K1C hypertensive rats, while it had no effect in the control rats. Endothelial destruction potentiated the vasorelaxant effect of ANP on basal tone in 2K1C rats. A similar potentiation of the ANP response was observed by pre-treatment with Nω-nitro-L-arginine methyl ester (L-NAME) or methylene blue in aortic rings with endothelium. Treatment with calcium-free Krebs decreased basal tone and abolished ANP-response. These effects were observed only in aortic rings from 2K1C rats. Similarly, staurosporine and calphostin C, inhibitors of protein kinase C (PKC), lowered basal tone and abolished ANP-response in hypertensive rats. Acetylcholine had a small relaxant action on the basal tone of unrubbed aorta, which was attenuated in 2K1C rats as compared with control rats. These results demonstrate that ANP has a vasorelaxant effect on basal tone in 2K1C renovascular hypertension. Inhibition of ANP effects on basal tone by calcium-free Krebs and PKC antagonists suggests that altered Ca2+-active tone is involved in hypertension, that modifies the response of vascular smooth muscle to the ANP.