Inhibitory Effects of Insulin and Aggregatory Response in Hypertensive Subjects on Intracellular Calcium of Platelets Are Impaired with Insulin Resistance

To determine the effects of insulin on intracellular calcium and platelet aggregatory responses in hypertensive subjects with insulin resistance, we measured insulin sensitivity in terms of glucose disposal rate (GDR) by the hyperinsulinemic euglycemic clamp technique (GC) in 14 non-diabetic untreated hypertensive subjects, and determined basal ([Ca2+];) and thrombin-stimulated (T-[Ca2+];) platelet-free calcium concentrations and thrombin-stimulated platelet aggregatory response (AG) before (PRE[Ca2+];, T-PRE[Ca2+];, and PRE AG, respectively) and during (POST[Ca2+];, T-POST[Ca2+];, and POST AG, respectively) GC. As a control for GC, vehicle (normal saline) was infused on another day. No significant difference was observed between PRE[Ca2+]; and POST[Ca2+];, T-PRE[Ca2+]; and T-POST[Ca2+];, or PRE AG and POST AG. GDR inversely correlated with d[Ca2+]; (POST[Ca2+];PRE[Ca2+];, r= -0.75, p < 0.02), dT-[Ca2+]; (T-POST[Ca2+]; T-PRE[Ca2+];, r= -0.63, p < 0.02) and dAG (POST AG PRE AG, r = -0.67, p < 0.01). No significant changes were observed in these variables during vehicle infusion. [Ca2+];, T-[Ca2+];, and AG decreased during GC as compared with baseline in hypertensive subjects with normal insulin sensitivity, but were unchanged in those with insulin resistance, suggesting that the vasodilatory and anti-platelet aggregatory effects of insulin are im-