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 resistance, it is unclear which defect is primary. We therefore compared normotensive Sprague-Dawley male rats who drank N-nitro-L-arginine methyl ester (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 second day of L-NAME treatment, and remained elevated throughout the study, in contrast to the rats drinking water (P < .001). Weight rose similarly in both groups. OGTT were performed after 2 weeks of L-NAME. Serum glucose and insulin responses, assessed by two-way ANOVA, were similar in the two groups (P = NS). In summary, L-NAME administration resulted in hypertension, but not a deterioration in glucose tolerance in diet-controlled Sprague-Dawley rats. We conclude that the insulin resistance of some hypertensive states is not the result of hypertension per se, or increased vasoconstriction, such as might result from inhibition of endogenous nitric oxide synthesis, but rather indicates a fundamental metabolic disorder.
Swislocki
A
A
Medical Service, Department of Veterans Affairs, Northern California System of Clinics, Martinez 94553, USA.
Eason
T
T
Kaysen
G A
GA
D000284:Administration, Oral; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D018149:Glucose Intolerance / Q000139:chemically induced; D006973:Hypertension / Q000139:chemically induced*; D007333:Insulin Resistance; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester