ORAL-ADMINISTRATION OF THE NITRIC-OXIDE BIOSYNTHESIS INHIBITOR, N-NITRO-L-ARGININE METHYL-ESTER (L-NAME), CAUSES HYPERTENSION, BUT NOT GLUCOSE-INTOLERANCE OR INSULIN-RESISTANCE, IN RATS

While essential hypertension may be characterized by insulin resistanc e, it is unclear which defect is primary. We therefore compared normot ensive Sprague-Dawley male rats who drank N-nitro-L-arginine methyl es ter (L-NAME, 1 mg/mL in distilled water), with control rats who drank distilled water. Blood pressure was measured noninvasively, weight was controlled by dietary restriction, and glucose tolerance was assessed via oral glucose tolerance tests (OGTT). Blood pressure rose by the s econd day of L-NAME treatment, and remained elevated throughout the st udy, in contrast to the rats drinking water (P <.001). Weight rose sim ilarly in both groups. OGTT were performed after 2 weeks of L-NAME. Se rum glucose and insulin responses, assessed by two-way ANOVA, were sim ilar in the two groups (P = NS). In summary, L-NAME administration res ulted in hypertension, but not a deterioration in glucose tolerance in diet-controlled Sprague-Dawley rats. We conclude that the insulin res istance of some hypertensive states is not the result of hypertension per se, or increased vasoconstriction, such as might result from inhib ition of endogenous nitric oxide synthesis, but rather indicates a fun damental metabolic disorder.