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 μU/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 agematched 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/1 (WKY), 60 ± 10 nmol/L (Wistar), and 28 ± 8 nmol/L (SHR), (P< .01 ν 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 ν normotensive) in cells from 17week-old rats. Insulin increased angiotensin IIstimulated [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. Blunted attenuation by insulin of angiotensin II-stimulated [Ca2+]i responses as well as the prolonged recovery rate to basal values in cells from SHR could be manifestations of VSMC insulin resistance in genetically hypertensive rats.