Salt-induced hypertension in rats alters the response of isolated aortic rings to cromakalim.
The effect of cromakalim, an opener of ATP-sensitive potassium (KATP) channel, on precontracted aortic rings from control and salt-loaded rats was studied in Sprague-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/alpha-chloralose anaesthesia. Isolated aortic rings were mounted in tissue baths for isometric tension measurement. The sodium-potassium adenosine triphosphatase (Na-K ATPase) 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(-7) M noradrenaline or 60 mM potassium chloride (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 from the control rats; rings from salt-loaded rats showed significantly less relaxation 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 the 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.
Obiefuna
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Department of Basic Medical Sciences, University of the West Indies, Mona, Kingston 7, Jamaica. obiefuna@uwimona.edu.jm
Obiefuna
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D000251:Adenosine Triphosphatases / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D019806:Cromakalim / Q000008:administration & dosage / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D015221:Potassium Channels; D017673:Sodium Chloride, Dietary; D014665:Vasodilator Agents; D019806:Cromakalim; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase