The Effect of Calcium Antagonist on Norepinephrine-Induced 86Rb Efflux in Obese Zucker Rats
The obese Zucker rat is a model for obesity which exhibits an insulin resistance characterized by hyperinsulinemia and mild hyperglycemia (Kurtz, et al., 1989). There is also an increased incidence of hypertension in the obese Zucker rat which is a common observation in human obesity. Although a variety of factors have been proposed to account for the elevated blood pressure (Dornfeld et al., 1987; Levy et al., 1989), the observation that total peripheral resistance is elevated in the hypertensive obese rats (Shehin et al., 1989) suggests that vasoconstriction of vascular smooth muscle may be a contributing factor. Vascular smooth muscle from obese Zucker rats exhibits an increased sensitivity to a variety of agonists including phenylephrine, serotonin, and potassium (Zemel et al., 1990). This non-specific supersensitivity suggests that the enhanced vascular reactivity is due to a functional alteration in vascular smooth muscle itself rather than via selective receptor-mediated events. Insulin has both direct and indirect effects on calcium metabolism in a variety of tissues (Levy et al., 1989). Since both insulin resistance and hyperinsulinemia occur in the obese Zucker rat, it has been suggested that altered calcium metabolism in vascular smooth muscle may underlie the increased vascular reactivity. The recent report that both the CaATPase activity and 45Ca efflux from aorta of obese Zucker rat are decreased compared to normotensive lean controls is consistent with this proposal. Recently it has been reported that insulin also modulates potential sensitive calcium channels (POC) in some tissues (Zierler and Fong, 1988). Calcium entry through this pathway plays a dominant role in both depolarization-induced as well as receptor-mediated stimulation of vascular smooth muscle (Cauvin et aL, 1983). Therefore, it was of interest to compare the effect of the calcium antagonist diltiazem, which blocks calcium entry through the POC, on norepinephrine stimulation of aorta from obese Zucker and age-matched lean control rats.
KeywordsVascular Smooth Muscle Calcium Antagonist Vascular Reactivity Calcium Entry Lean Control
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