Altered Endothelial Modulation of Vasoconstriction in Chronic Two-Kidney, One Clip Hypertensive Rats / 대한신장학회잡지

ABSTRACT

It is well known that the endothelium plays an important role in the circulation by modulating contractile responses of vascular smooth muscle. This study was designed to investigate the alterations and the mechanisms of endothelial modulation in chronic 2-kidney, 1 clip(2K1C) hypertensive rats. 2K1C hypertension was made by clipping the left renal artery and age-matched control rats received a sham treatment. Aortic rings were mounted in tissue baths for measurement of isometric tension. In rings with endothelium, norepinephrine evoked concentration-dependent contraction. Endothelium removal markedly enhanced the contraction, and the responses were less pronounced in 2K1C rats than control rats. Similar fashion of the contractions by endothelium removal was observed with norepinephrine and the alpha1 drenoceptor agonist phenylephrine in control rats, while phenylephrine did not alter the contraction by endothelium removal in 2K1C rats. The alpha2 drenoceptor agonist clonidine also greatly enhanced the contraction after endothelium removal, however the endothelial inhibition was still shown in 2K1C rats. In contrast to norepinephrine-induced contractions, the enhancement of serotonin-or prostaglandin F2alpha - induced contractions after endothelium removal was small and similar in 2K1C and control rats. NG-nitro-L-arginine methyl ester enhanced the contraction induced by agonists in aortic rings with endothelium, which was similar to the response in rings without endothelium. The relaxation response to acetylcholine was attenuated in 2K1C rats, while the response to sodium nitroprusside remained unaltered. These results indicate the endothelium plays an inhibitory role against contractions in rat aorta by releasing nitric oxide, but the characteristics of the endothelial inhibition are not identical against various agonists. The negative endothelial modulation is more pronounced during alpha1 and alpha2 renoceptor- mediated contractions than during contractions mediated by other receptors. In addition, the inhibitory role of the endothelium against alpha1 drenoceptor agonist-induced contraction is impaired in 2K1C renal hypertension.