Influence of Vascular Endothelium in Contraction Induced by Phorbol Ester in Renal Hypertensive Rats

Abstract

Background and Objectives:The vascular endothelium plays an important role in circulation, by modulating the contractile responses of the arterial smooth muscle. This study was aimed at investigating the possible role of the endothelium in the contractile response to phorbol 12, 13-dibutyrate (PDB) in chronic two-kidney, one clip (2K1C) hypertensive rats. Materials and Methods:2K1C hypertension was induced by clipping the left renal artery of the study rats, with age-matched rats receiving a sham treatment, which served as controls. The thoracic aortae were mounted in tissue baths to measure the isometric tension. Results:The PDB showed a dosedependent contraction, with larger responses in the 2K1C hypertensive than the sham-clipped control rats. Nnitro-L-arginine (L-NNA) and methylene blue (MB) induced an increase in the tension in the presence of PDB, and the potentiating effects of L-NNA or MB were attenuated in the 2K1C rats as compared to the controls. Staurosporine, an inhibitor of protein kinase C, completely inhibited the contractile response to PDB, as well as enhancing the effects of L-NNA and MB. Removal of the endothelium abolished the contractile responses to LNNA and MB in both the 2K1C and control rats. The relaxation responses to acetylcholine in the aortic rings precontracted with PDB were also attenuated in the 2K1C rats, and L-NNA prevented the effect of the acetylcholine-induced relaxation. Indomethacin, glibenclamide and iberiotoxin did not affect the PDB responses in both the 2K1C and control rats. Conclusion:These results indicate the endothelium plays an inhibitory role against PDB-induced contraction in rat aortae, by releasing nitric oxide, and the inhibitory role of the endothelium is impaired in 2K1C renal hypertension. (Korean Circulation J 2003;33 (11):1036-1043)