Role of sarcoplasmic reticulum in arterial contraction: comparison of ryanodines's effect in a conduit and a muscular artery.

Abstract

Ryanodine interferes with sarcoplasmic reticulum function in various types of muscle; in vascular smooth muscle, it can inhibit contractions that depend on sarcoplasmic reticulum calcium release, probably by depleting the sarcoplasmic reticulum calcium store. We tested ryanodine and calcium channel blockers (verapamil, diltiazem, and nitrendipine) on small rings of rat thoracic aorta (RA) and bovine tail artery (BTA) to determine the relative contributions of sarcoplasmic reticulum calcium release and gated calcium entry to contractions induced by norepinephrine, caffeine, and 100 mM K depolarization. Ryanodine blocked caffeine contractions in both tissues and attenuated norepinephrine responses (by 52% in RA, 14% in BTA) but minimally altered potassium contractions. Calcium channel blockers almost completely abolished potassium contractions and reduced norepinephrine contractions (by 45% in RA, 82% in BTA) but hardly affected caffeine responses. The blocking effects of ryanodine and calcium channel antagonists on the norepinephrine responses were additive. Ryanodine had no effect on baseline tension in the standard media; however, when calcium extrusion via Na-Ca exchange was inhibited by low external sodium (0-calcium, low-sodium solution), tension increased progressively after introduction of ryanodine. This indicates that the sarcoplasmic reticulum calcium released by ryanodine then accumulated in the cytosol and activated contraction; restoration of external sodium caused prompt relaxation. The smaller effects of caffeine and ryanodine in BTA indicate that sarcoplasmic reticulum plays a less important role in calcium control in this tissue, with gated calcium entry dominating. These functional findings are correlated with electron-microscopic evidence that BTA has about 60% less sarcoplasmic reticulum than does RA. Ryanodine appears to be a useful tool for determining the functional relevance of sarcoplasmic reticulum for contraction in different arterial smooth muscles.