INSULIN-RESISTANCE AFTER HYPERTENSION INDUCED BY THE NITRIC-OXIDE SYNTHESIS INHIBITOR L-NMMA IN RATS

To explore the relationship between insulin resistance and hypertensio n, we examined whether acute induction of hypertension can engender in sulin resistance. For this purpose we measured rates of insulin-mediat ed glucose uptake in awake unstressed rats with the euglycemic hyperin sulinemic (12 mu m . kg(-1). min(-1)) clamp technique during infusions of saline alone or after induction of hypertension by bolus administr ation of N-G-monomethyl-L-arginine (L-NMMA, 30 and 15 mg/kg), a compet itive inhibitor of nitric oxide synthase. Arterial pressure was simila r to 20% greater with L-NMMA bolus than with saline alone. Isotopicall y determined steady-state rates of glucose uptake were 36 +/- 1 mg . k g(-1). min(-1) during saline alone and 26 +/- 2 and 19 +/- 1 mg . kg(- 1). min(-1) with low- and high-dose L-NMMA(P < 0.001 vs. saline), resp ectively. To rule out that insulin resistance induced by L-NMMA was ad renergically mediated, clamp studies were repeated with alpha- and bet a-blockade. Rates of glucose uptake remained similar to 20% below thos e observed with saline alone (P < 0.001). A significant inverse correl ation was observed between the height of the blood pressure and the ra te of glucose uptake (r = 0.32, P = 0.04). In conclusion, acute induct ion of hypertension with L-NMMA can cause marked insulin resistance. W e postulate that reduced skeletal muscle perfusion and/or sympathetic nervous system activation may contribute to insulin resistance induced by L-NMMA.