Myogenic Activation and Calcium Sensitivity of Cannulated Rat Mesenteric Small Arteries

From the Academic Medical Center, University of Amsterdam (Netherlands), Department of Medical Physics and Cardiovascular Research Institute.

Correspondence and reprint requests to Dr E. VanBavel, Academic Medical Center, PO Box 22700, 1100 DE Amsterdam, the Netherlands. E-mail e.vanbavel{at}amc.uva.nl

Abstract—Pressure-induced activation of vascular smooth muscle may involve electromechanical as well as nonelectromechanical coupling mechanisms. We compared calcium-tone relations of cannulated rat mesenteric small arteries during pressure-induced activation, depolarization (16 to 46 mmol/L K⁺), and ₁-adrenergic stimulation (1 µmol/L phenylephrine). The intracellular calcium concentration was expressed as the fura-2 ratio, normalized to the maximal and minimal ratios. In order to compare activation levels at various pressures, tone was expressed as the ratio of active wall tension to the maximal active tension. The passive and maximal active pressure-diameter relations needed for the calculation of tone were determined in a separate set of experiments, using isometric loading of cannulated vessels. Pressure steps from 20 to 60 and then to 100 mm Hg caused a modest rise of calcium. Nifedipine (1 µmol/L) blocked both the calcium rise and the resulting myogenic responses. Electromechanical coupling could not fully account for the myogenic response: the calcium sensitivity, defined as the slope of the calcium-tone relation, was five times higher during pressure-induced activation compared with potassium stimulation and twice as high as the sensitivity during ₁-adrenergic stimulation. We therefore conclude that the myogenic response involves a small but necessary rise in calcium due to influx through L-type calcium channels, as well as a nonelectromechanical coupling mechanism that greatly enhances the calcium sensitivity of the contractile machinery.

Key Words: Ca²⁺ channel • myogenic response • vascular smooth muscle • mesenteric artery • rat