Impaired insulin-mediated vasodilation has been implicated in hypertension that is associated with the metabolic syndrome. The aim of this study was to determine whether an abnormality in membrane fatty acid composition was related to a weakening of insulin's inhibitory effect on agonist-stimulated intracellular free calcium elevation. Mild to moderate hypertensive patients (n = 27) and normotensive controls (n = 11) were studied. Hypertensive patients were divided into normoinsulinemic patients (n = 14) and hyperinsulinemic patients (n = 13) according to the area under the curve of plasma insulin concentrations during a 75-g oral glucose tolerance test. Nonstimulated and arginine-vasopressin (AVP) (1 micromol/l)-stimulated intraplatelet free calcium concentrations (p[Ca(2+)](i)) were measured with or without insulin (100 microU/ml) preincubation. Platelet membrane fatty acid composition, intraerythrocyte sodium content, and the ouabain-sensitive sodium efflux rate constant (K (os)) of erythrocytes were also determined. Insulin preincubation reduced AVP-stimulated p[Ca(2+)](i) elevation in both normotensive controls and hypertensive patients. The inhibitory effect of insulin on AVP-stimulated elevation of p[Ca(2+)](i) (%Inhibition) was significantly (P < 0.05) blunted in hyperinsulinemic hypertensive patients (9.7% +/- 2.4%) as compared to normoinsulinemic hypertensive patients (17.4% +/- 2.7%) and normotensive controls (16.9% +/- 1.7%). In hypertensive patients, the %Inhibition was correlated negatively with saturated fatty acids (SFA) (r = -0.51, P < 0.05) and systolic blood pressure (r = -0.44, P < 0.05), and correlated positively with membrane polyunsaturated fatty acids (PUFA) (r = 0.53, P < 0.01) and K (os) (r = 0.53, P < 0.005). Multiple regression analysis showed that SFA, PUFA, and K (os) were the significant variables for %Inhibition. These findings indicate that an increase in SFA and a decrease in PUFA may cause insulin insensitivity in cellular calcium and sodium handling in hypertension with hyperinsulinemia.