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

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)

The effects of potassium channel agonists, cromakalim and adenosine, in diabetic rat hearts

INTRODUCTION: This study was designed to look at ATP sensitive potassium channels (KATP-sc) in diabetic male Sprague-Dawley rat hearts. Diabetes mellitus was induced using streptozocin (ip). KATP-SC can be found in pancreatic B-cells, cardiac muscle, skeletal muscle, neurones, hypothalamus and smooth muscle. Cromakalim and adenosine were used to construct concentration-response curves. These drugs are KATP-SC openers that cause shortening of action potential duration and hyperpolarisation. This is a novel study as there is a sparsity of information on the effect of KATP-SC openers on the hearts of diabetic animals. We therefore hypothesised that cromakalim and adenosine may have both an effect on the electrical activity as well as the contractility in the diabetic myocardium. METHODS: Male Sprague-Dawley rats (150-250 gm) were treated with streptozotocin (STZ) (60 mg/Kg i.p.). All animals were kept under identical living conditions and allowed free access to food and water for 1 week. Animals were then sacrificed after being anaesthetised with 60 mg/Kg pentobarbital containing 1000 Units/ml heparin. Hearts were being rapidly excised, placed in 4 degrees C. Krebs-Henseleit buffer and mounted in a Langendorff system. Concentration-response curves were constructed for cromakalim (0.01nM-0.1uM), and adenosine (0.1uM-100uM). Parameters measured were heart rate (HR), P-R and QRS intervals, systolic pressure (SP), diastolic pressure (DP) and developed pressure (Dev. Pre.). RESULTS: The results found for cromakalim in diabetic rats and adenosine in normal rats mirrored what has been found in previous studies for these drugs in non-diabetic animals, namely, a decrease in HR, an increase in P-R and QRS and a decrease in SP and Dev. Pre. However, adenosine in diabetic rats showed some unexpected results such as a decrease in P-R, and an increase in SP and Dev. Pre. It is possible that the diabetic state interferes significantly with the actions of adenosine but not as significantly with those of cromakalim. Conclusion: The results indicate that adenosine may not be cardioprotective in diabetic animals. This conclusion may be drawn from the fact that P-R interval decreased with increasing concentrations of adenosine. This may lead to the production of arrhythmias such as life threatening ventricular tachycardia or fibrillation (AU)