Interaction between L-type Ca²⁺ channels and sarcoplasmic reticulum in the regulation of vascular tone in isolated rat small arteries

Summary: A dysfunction of the sarcoplasmic reticulum (SR) causes an increase in the myogenic tone of rat skeletal muscle small arteries (A(SK)), but not that of mesenteric small arteries (A(MS)). We hypothesized that the difference depends on the activity of voltage-dependent Ca²⁺ channels in these vessels. To test this, we measured the membrane potential of these vessels and examined ryanodine-induced constrictions by manipulating the activity of voltage-dependent Ca²⁺ channels. The isolated vessels were cannulated to control the transmural pressure. To assess the vascular tone, the inner diameter was measured with a video-digitizing system. The membrane potential of A(SK) was more depolarized between 20 to 100 mm Hg of transmural pressure. A(MS) was not constricted by the Ca²⁺ channel agonist Bay K 8644 (1 nM-1 μM) alone, but substantially constricted in the presence of ryanodine (1 μM). Ryanodine also augmented the KCl (20 mM)-induced constriction. In A(sk), the Ca²⁺ channel blocker nisoldipine fully dilated the ryanodine-induced constriction; however, the ryanodine-induced constriction was less susceptible to nisoldipine than was the myogenic and phenylephrine-induced constriction caused mainly by increased Ca²⁺ influx. In conclusion, the contribution of the SR function to Ca²⁺ metabolism depends on the activity of dihydropyridine-sensitive Ca²⁺ channels. The dysfunction of SR by ryanodine may impair the Ca²⁺ extrusion rather than increase Ca²⁺ influx in rat small arteries.