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

Paul R. Standley, Jeffrey L. Ram, James R. Sowers

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

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 × 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.

Original languageEnglish (US)
Pages (from-to)1693-1699
Number of pages7
JournalEndocrinology
Volume133
Issue number4
DOIs
StatePublished - Oct 1993
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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