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 after 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-thiourea (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 absence of external calcium, the inhibition of the Na(+)-Ca2+ exchange by NiCl2 also enhanced the ANG II-induced [Ca2+]i increase. Inhibition of 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-methylpiperazine blocked the enhancing effect of NiCl2 on ANG II-induced [Ca2+]i increase. The inhibition of the Na(+)-Ca2+ exchange did not enhance the increase in [Ca2+]i induced by ANG III, NE, or thapsigargin. The AVP-induced changes in [Ca2+]i were not significantly different in the presence or absence of NiCl2. It is concluded that the recovery of resting [Ca2+]i after stimulation by ANG II is mediated by calcium efflux via the Na(+)-Ca2+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhu
Z
Z
Medizinische Universitäts-Poliklinik, University of Münster, Germany.
Tepel
M
M
Neusser
M
M
Zidek
W
W
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D011921:Rats, Inbred WKY; D019831:Sodium-Calcium Exchanger; D013268:Stimulation, Chemical
D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D000804:Angiotensin II; D002118:Calcium