SENSITIZATION OF ISOLATED CANINE CORONARY-ARTERIES TO CALCIUM-IONS AFTER EXPOSURE TO CHOLESTEROL

The abundance of membrane cholesterol is an important determinant of the functional properties of biomembranes. To determine whether arterial smooth muscle acquires altered contractile properties in a high cholesterol environment, isolated canine coronary arteries were exposed to cholesterol in a stable aqueous solution. Cholesterol, 10-12 to 10-10 M, was an efficacious vasoconstrictor, as maximum contractions equaled those obtained with 15 mM KCl. Antiadrenergic interventions, including chemical sympthectomy in vivo with 6-hydroxydopamine and α- and β-adrenergic blockade with phentolamine and L-propranolol (both 10-6 M), did not significantly attenuate the contraction. However, response to cholesterol were abolished completely by (±)-verapamil (10-6 M). Cholesterol in picomolar concentration enhanced the constrictor effects of CaCl2 and KCl, both in the presence and absence of α- and β-adrenergic blockade. Increases in tone in response to graded elevations in the CaCl2 concentration (0-2 mM) were augmented up to 1.5-fold by 10-162 M cholesterol (P< 0.01).Results indicate that cholesterol sensitizes isolated coronary arteries to external Ca2+ by a nonadrenergic mechanism. The findings are consistent with the hypothesis that acquisition of membrane cholesterol may alter the contractile properties of coronary arterial smooth muscle, a phenomenon that could play a role in the pathophysiology of atherosclerotic heart disease.