Endocrinology, Vol 133, 1693-1699, Copyright © 1993 by Endocrine Society

ARTICLES

Insulin attenuation of vasopressin-induced calcium responses in arterial smooth muscle from Zucker rats

PR Standley, JL Ram and JR Sowers
Division of Endocrinology and Hypertension, Wayne State University School of Medicine, Detroit, Michigan 48202.

Insulin attenuates agonist-induced vascular contractility of aortic rings and decreases vasopressin (AVP)-elicited increases in vascular smooth muscle cell (VSMC) intracellular calcium ([Ca2+]i). To determine if insulin's effects on AVP-induced [Ca2+]i responses are altered in an insulin-resistant and hypertensive state, we studied vascular smooth muscle calcium responses in VSMC derived from Zucker lean and obese rats. AVP concentration-response experiments revealed that VSMC derived from obese animals exhibited exaggerated [Ca2+]i responses over the range of 1 x 10(-10) to 1 x 10(-7) M AVP compared to lean controls (P < 0.05, by multiple analysis of variance). Insulin treatment (7 x 10(-7) M) decreased the [Ca2+]i response to 1 nM AVP by 66 +/- 8% and 71 +/- 9% in lean and obese VSMC, respectively. Similar decreases were observed with the 10 nM AVP stimulus (41 +/- 9% and 61 +/- 7%, for lean and obese, respectively). AVP receptor binding studies revealed that exaggerated [Ca2+]i responses in obese VSMC were not due to alterations in AVP-binding properties (no significant differences in ID50, Kd, or binding capacity in lean and obese VSMC preparations). In addition, insulin treatment (1 x 10(-7) M) resulted in no differences in AVP receptor-binding properties in either cell line. Therefore, exaggerated [Ca2+]i responses in obese VSMC are most likely due to a postreceptor abnormality. These abnormalities in VSMC [Ca2+]i metabolism preceed and may play a role in the development of hypertension in the Zucker obese rat. Although insulin resistance in Zucker obese rats has been demonstrated in several tissues, VSMC [Ca2+]i responses to AVP are, nonetheless, similarly attenuated by insulin in obese and lean VSMC preparations.

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