Insulin attenuation of vasopressin-induced calcium responses in arterial smooth muscle from Zucker rats.
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.
Standley
P R
PR
Division of Endocrinology and Hypertension, Wayne State University School of Medicine, Detroit, Michigan 48202.
Ram
J L
JL
Sowers
J R
JR
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism / Q000494:pharmacology*; D001158:Arteries / Q000378:metabolism*; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker / Q000378:metabolism*; D017483:Receptors, Vasopressin / Q000378:metabolism; D012016:Reference Values
D007328:Insulin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D002118:Calcium