ROLE OF NA-CA2+ EXCHANGE IN AGONIST-INDUCED CHANGES IN CYTOSOLIC CA2+IN VASCULAR SMOOTH-MUSCLE CELLS()

Changes in cytosolic free calcium concentration ([Ca2+](i)) induced by angiotensin II (ANG II), arginine vasopressin (AVP), angiotensin III (ANG III), norepinephrine (NE), or thapsigargin were investigated afte r inhibition of the Na+-Ca2+ exchange in vascular smooth muscle cells (VSMC) from Wistar-Kyoto rats by use of the fluorescent dye technique. The ANG II-induced peak [Ca2+](i) increase was significantly enhanced after inhibition of Na+-Ca2+ exchange by NiCl2 or 1,3-dimethyl-2-thio urea (DMTU): control, 99 +/- 9 (SE) nM (n = 64); NiCl2, 181 +/- 23 nM (n = 23; P < 0.01); DMTU, 182 +/- 35 nM (n = 10; P < 0.05). In the abs ence of external calcium, the inhibition of the Na+-Ca2+ exchange by N iCl2 also enhanced the ANG II-induced [Ca2+](i) increase. Inhibition o f Na+-Ca2+ exchange by removal of external sodium, which was replaced by choline, augmented the ANG II-induced [Ca2+](i) increase to 174 +/- 26 nM (n = 11; P < 0.05 compared with control). The inhibition of the protein kinase C activity by isoquinoline-sulfonyl-O-2-methylpiperazi ne blocked the enhancing effect of NiCl2 on ANG II-induced [Ca2+](i) i ncrease. The inhibition of the Na+ Ca2+ exchange did not enhance the i ncrease in [Ca2+](i) induced by ANG III, NE, or thapsigargin. The AVP- induced changes in [Ca2+](i) were not significantly different in the p resence or absence of NiCl2. It is concluded that the recovery of rest ing [Ca2+](i) after stimulation by ANG II is mediated by calcium efflu x via the Na+-Ca2+ exchange. In addition, the pathway by which elevate d [Ca2+](i) is returned to baseline values is not uniform but depends on the stimulating agonist.