GLUCOSE-TOLERANCE AND INSULIN ACTION IN RATS WITH RENOVASCULAR HYPERTENSION

To test whether hypertension can cause hyperinsulinemia or insulin resistance, we performed intravenous glucose tolerance tests at 1 month and euglycemic clamps at 3 months after induction of two-kidney, one clip renovascular hypertension in rats. At 1 month, systolic pressure was higher in 21 clipped than in 12 control animals (161 +/- 5 mm Hg, range 134-187 mm Hg versus 119 +/- 3 mm Hg, range 108-146 mm Hg; p < 0.001). Glucose tolerance, assessed as the glucose fractional disappearance rate between 3 and 11 minutes after the glucose injection, was similar in the clipped and sham groups (0.059 +/- 0.002 versus 0.056 +/- 0.002 min-1, respectively; p > 0.4). The total area under the insulin curve during glucose tolerance tests was also similar in the clipped and sham groups (926 +/- 95 versus 869 +/- 126 microunits/ml x min; p > 0.4). There was no significant relation between systolic blood pressure and insulin area during glucose tolerance tests in the clipped group, but there was a positive rectilinear relation in the control group (r = 0.66; p = 0.01). Fourteen animals had euglycemic clamps 2 months after glucose tolerance tests. At that time, systolic pressure (direct femoral measurement) was higher in the seven clipped animals (189 +/- 13 mm Hg versus 122 +/- 5 mm Hg in controls; p < 0.001). Insulin infusions of 1 and 4 milliunits/min/kg body wt effected similar plasma insulin levels in the two groups. Glucose requirements during 1 milliunit/min/kg insulin were higher in the clipped than the control group (6.1 +/- 0.7 versus 2.4 +/- 0.6 mg/min/kg, respectively; p < 0.001). Glucose requirements during 4 milliunits/min/kg insulin were similar in the two groups (28.4 +/- 1.1 versus 26.8 +/- 2.8 mg/min/kg; p > 0.5). Our data indicate that neither mechanisms leading to renovascular hypertension nor elevated blood pressure per se caused sustained hyperinsulinemia or insulin resistance in this rat model.