Protein kinase C contributes to enhanced calcium sensitivity in coronary arteries from hypercholesterolemic swine

Abstract

Previous studies have reported enhanced KCl-mediated constriction despite reduced smooth muscle cell calcium channel current in coronary arteries from hypercholesterolemic swine. We tested the hypothesis that coronary arteries of hypercholesterolemic pigs are more sensitive to calcium due to an activation of protein kinase C (PKC). Male Yucatan miniature swine were randomly assigned to a control (CON) or high fat/high cholesterol (HC) diet for 23 wks and then killed. Vascular reactivity of rings isolated from the left anterior descending coronary artery was studied using standard isometric techniques. Rings from HC animals constricted with greater force per unit of intracellular calcium in response to KCl. Additionally, the response to increasing calcium concentrations was greater in permeabilized rings from HC compared with CON animals. Rings isolated from HC animals also exhibited enhanced maximal constriction to KCl. The broad-spectrum PKC inhibitor calphostin C (1 μM) attenuated this constriction to a greater extent in arteries from HC compared to CON animals; however, the conventional PKC isoform-selective inhibitor bisindolylmaleimide (1 μM) had no effect in either group. We conclude that the increase in calcium sensitivity of the coronary vasculature in HC animals is attributable at least in part to an increased contribution of the novel PKC isoforms. Support: AHA 0330252N