Na-Ca Exchange, Myoplasmic Ca Concentration, and Contraction of Arterial Smooth Muscle

Na-Ca exchange is proposed to be an important regulator of myoplasmic intracellular Ca concentration ([Ca]|) and contraction in vascular smooth muscle. We investigated the role of Na-Ca exchange in regulating [Ca], in swine carotid arterial tissues that were loaded with aequorin to allow simultaneous measurement of [Ca], and force. Reversal of Na-Ca exchange, by reduction of extracellular Na concentration ([Na]o) to 1.2 mM, induced a large increase in aequorin-estimated [Ca]| and a low [Ca], sensitivity. The contraction induced by 1.2 mM [Na], was partially caused by depolarization and opening of L-type Ca channels because 10 fiM diltiazem partially attenuated the 1.2 mM [Na]0-induced increases in [Ca ],. High dose ouabain (10 fiM), a putative endogenous Na,KATPase inhibitor, increased both [Ca]| and force. However, the increases in [Ca]| and force were mostly blocked by 10 /iM phentolamine, suggesting the predominant effect of ouabain was to increase norepinephrine release from nerve terminals. In the presence of 10 fiM phentolamine, 10 fiM ouabain slightly accentuated 1 ftM histamlne-induced increases in [Ca], and force. The ouabain dose necessary to induce contraction in the absence of phentolamine was significantly less than the ouabain dose necessary to accentuate histamine-induced contractions in the presence of phentolamine. These results suggest that Na-Ca exchange exists in swine arterial smooth muscle. These data also suggest that ouabain (which should increase [Na], and inhibit Na-Ca exchange) primarily enhances contractile function in the swine carotid artery by releasing catecholamines from nerve terminals; direct action of Na,K-ATPase inhibitors on smooth muscle appears to occur only with very high doses. (Hypertension 1992;19-308-313)