Comparison of calcium import as a function of contraction in the aortic smooth muscle of Sprague-Dawley, Wistar Kyoto and spontaneously hypertensive rats.

Abstract

Genetic variations of far-reaching consequences have been established between spontaneously hypertensive rats (SHR) and their controls, Wistar Kyoto rats (WKY). The SHR strain is the most widely used model for the study of genetic hypertension. Calcium homeostasis in the vascular smooth muscle (VSM) is controlled by calcium channels and calcium pumps located in both VSM and the overlying endothelial cells that line the large blood vessels and the heart. Hypertension adversely affects calcium homeostasis. Investigations on the import of calcium from extracellular spaces with alpha1-adrenergic stimulation as a function of contractility of VSM cells in SHR and WKY were made and compared with the contractility observed in VSM cells of Sprague-Dawley (CD) rats. Experiments were performed on rings from thoracic aortas of three strains with endothelial lining intact or removed to discern the paracrine control of endothelium on contractility in response to calcium import. The internal stores of Ca2+ were depleted by repeated alpha 1-adrenergic stimulation with phenylephrine (PE) and refilling of these stores was prevented by cyclopiazonic acid (CPA) and/or thapsigargin (TG), two known inhibitors of Ca2+ATPase, the enzyme that drives sarcoplasmic calcium pumps. The two components of tonic muscular contraction, T I and T II, which are known to be due to the flow of Ca2+ from the extracellular gradient controlled via the poly-phosphoinositide cascade and nifedipine sensitive Ca2+ channels were found to be variable among these strains. Implications of these variations are discussed in this report