Enhanced vascular contractile responses in insulin resistance may be due to altered voltage-dependent Ca2+ channel function, contributing to the pathogenesis of hypertension.
To investigate the role of hyperinsulinemia/insulin resistance in vasomotor tone regulation, we studied the effects of vasoactive substances on tension and intracellular free calcium concentration (Ca2+i) of aortic smooth muscle derived from rats that were made hyperinsulinemic by insulin infusion and from Zucker obese rats with insulin resistance. The tension and Ca2+i of fura 2-loaded aortic strip preparations without endothelium were simultaneously measured by using a fluorimeter. Ten male Wistar rats received a continuous subcutaneous infusion of insulin (18 nmol x kg(-1) x day(-1)) for 2 weeks with osmotic minipumps (INS group). A control group of 10 rats received vehicle. The plasma immunoreactive insulin concentration in the INS group increased to 930 +/- 54 pmol/l. The increase in Ca2+i and tension by KCl and phenylephrine (PE) were lower in the INS group without alteration of the Ca2+i-tension relationship. The responses to serotonin (5-HT) in the INS group were similar to those in the control group. In contrast, responses to KCl, PE and 5-HT were markedly enhanced in Zucker obese rats compared with those in Zucker lean rats. The pretreatment of aortic preparations from lean rats with Bay K8644 significantly enhanced the responses to KCl to the level observed in the preparations from obese rats; however, Bay K 8644 failed to affect the responses to KCl in obese rats. These results suggest that enhanced vascular contractile responses to vasoactive substances, possibly due to altered function of the voltage-dependent Ca2+ channel in vascular smooth muscle, may play an important role in the pathogenesis of hypertension in the insulin resistance syndrome.
Ouchi et al. (Mon,) studied this question.
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