Salt-Induced hypertension in rats alters the response of isolated aortic rings to cromakalim

ABSTRACT

The effect of cromakalim, an opener of ATP-sensitive potassium (K atp) channel, on precontracted aortic rings from control and salt-loaded rats was studied in spague-Dawley rats. Salt-loading experiments involved the induction of hypertension by 6-week feeding of 80 g sodium chloride(NaCl)per kilogram(kg) diet while the control diet had 3 g NaCl per kg diet. Blood pressure and heart rate were determined by cannulation of a femoral artery under urethane/a-chloralose anaesthesia. Isolated aortic rings were mounted in tissue baths for isometric tension measurement. The sodium-potassium adenosine triphosphstase (Na-KATPase) pump activity was measured by potassium(K)-induced relaxation (with or without ouabain) following precontraction with 10-7 M noradrenaline.The KATP channel was studied by measuring the relaxation response to cromakalim,precontracted with either 10-7M noradrenalineor 60mM potassiumchloride(KCl). The Na- k ATPase pump appeared to be inhibited during salt loading. ATPase inactivation was found to be ouabain sensitive but did not seem to affect subsequent K - induced contraction. Cromakalim produced relaxation of noradrenaline precontracted rings frem the control rats; rings from salt-loaded rats showed significantly less relaxtion than control(p<0.05) under similar conditions. During K-induced precontraction, cromakalim produced a weak biphasic response in the control rings-an initial relaxation and then a reversal. Cromakalim produced further contraction of K-induced precontraction in salt-loaded group. The results suggest that ATP-sensitive potassium channels and Na-K ATPase pumps on the vascular smooth muscle membrane may be deactivated in the development of hypertension during salt loading.(AU)