Blunted attenuation of angiotensin II-mediated Ca2+ transients by insulin in cultured unpassaged vascular smooth muscle cells from spontaneously hypertensive rats.
Insulin attenuates vasoconstrictor-stimulated intracellular calcium ([Ca2+]i) responses in cells from normotensive rats. To determine whether these effects may be altered in hypertension, this study assesses the effects of physiologic concentrations of insulin on angiotensin II-stimulated [Ca2+]i in primary unpassaged cultured vascular smooth muscle cells (VSMC) from mesenteric arteries from spontaneously hypertensive rats (SHR), Wistar Kyoto (WKY), and Wistar rats. [Ca2+]i was measured microphotometrically in cells from 3-, 9-, and 17-week-old rats by the Fura 2 methodology. Basal, angiotensin II-stimulated (1 nmol/L), and insulin-attenuated (70 microU/mL) angiotensin II-induced [Ca2+]i did not differ in VSMC obtained from 3-week-old WKY, Wistar, and SHR. Basal and angiotensin II-stimulated [Ca2+]i in VSMC from 9- and 17-week-old SHR was significantly greater (P < .01) than that in cells from age-matched WKY and Wistar rats. Insulin decreased angiotensin II-stimulated [Ca2+]i responses in all groups, but the effect was significantly blunted in cells from 9- and 17-week-old SHR. The magnitude of inhibition of angiotensin II-stimulated [Ca2+]i responses induced by insulin was 63 +/- 12 nmol/l (WKY), 60 +/- 10 nmol/L (Wistar), and 28 +/- 8 nmol/L (SHR), (P < .01 v normotensive) in cells from 9-week-old rats and 70 +/- 15 nmol/L (WKY), 67 +/- 12 nmol/L (Wistar), and 25 +/- 10 nmol/L (SHR) (P < .01 v normotensive) in cells from 17-week-old rats. Insulin increased angiotensin II-stimulated [Ca2+]i recovery rate to basal values in cells from WKY rats, but had no effect on the rate of recovery in VSMC from SHR. (ABSTRACT TRUNCATED AT 250 WORDS)
Touyz
R M
RM
Clinical Research Institute of Montréal, University of Montréal, Québec, Canada.
Tolloczko
B
B
Schiffrin
E L
EL
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured / Q000187:drug effects; D016232:Endothelins / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D007328:Insulin / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D016232:Endothelins; D007328:Insulin; D000804:Angiotensin II; D001127:Arginine Vasopressin; D002118:Calcium