HYPERTENSION WITHOUT PERIPHERAL INSULIN RESISTANCE IN SPONTANEOUSLY HYPERTENSIVE RATS

We performed euglycemic clamp studies with labeled glucose to measure insulin's effect on hepatic glucose output (HGO) and peripheral glucose clearance in eight conscious mobile spontaneously hypertensive rats (SHR) and eleven normotensive Wistar-Kyoto (WKY) rats age 9-10 wk. Systolic blood pressure was elevated in the SHR (P < 0.001), whereas means of 12-h-fasted plasma insulin (P > 0.4), glucose (P > 0.07), HGO (P > 0.25), and glucose clearance (P > 0.2) did not differ significantly between groups. Infusions of human insulin into SHR and WKY rats (1 and 1.5 mU.min-1.kg-1, respectively) during concomitant somatostatin administration reestablished basal insulinemia in both groups. Neither HGO (P > 0.15) nor glucose clearance (P > 0.3) differed significantly between SHR and WKY rats under those conditions. Somatostatin plus higher-dose insulin infusions (4 mU.min-1.kg-1 in SHR and 3 or 6 mU.min-1.kg-1 in WKY rats) resulted in physiological hyperinsulinemia in all rats. Insulin sensitivity, calculated as the increase in glucose clearance effected by an increase in circulating insulin during higher-dose insulin infusions, did not differ significantly between SHR and WKY groups (P > 0.3). HGO was completely suppressed in SHR and WKY rats during the higher-dose insulin infusions. Our data indicate that hypertension is present in SHR at an age when insulin-mediated glucose disposal is not different from age-matched WKY rats. These findings do not support a role for peripheral insulin resistance in the genesis of hypertension in SHR.