Insulin resistance following acute induction of hypertension with
the nitric oxide synthesis inhibitor l-nmma in rats.
Baron, Alain D., Jin-Su Zhu, Stephen Marshall, Orlando Irsula, Ginger
Brechtel, and Cheryl Keech.
Department of Medicine, Indiana University Medical Center,
Indianapolis, Indiana 46202, the Richard L. Roudebush Veterans
Affairs Medical Center, Indianapolis, Indiana 46202 and the Glaxo
Research Institute, Research Triangle Park, North Carolina 27709
APStracts 2:0089E, 1995.
To explore the relationship between insulin resistance and
hypertension we have examined whether acute induction of hypertension
can engender insulin resistance. For this purpose we have measured
rates of insulin mediated glucose uptake in awake unstressed rats
with the euglycemic hyperinsulinemic (12 mu/kg/min) clamp technique
during infusions of saline alone or after induction of hypertension
by bolus administration of L-N-monomethyl arginine (L-NMMA, 30 and 15
mg/kg), a competitive inhibitor of nitric oxide synthase. With L-NMMA
bolus arterial pressure was 20% greater than with saline alone.
Isotopically determined steady state rates of glucose uptake were
36+/-1 mg/kg/min during saline alone and 26+/-2 and 19+/-1 mg/kg/min
with low and high dose L-NMMA, p<0.001 vs. saline, respectively. To
rule out that insulin resistance induced by L-NMMA was adrenergically
mediated, clamp studies were repeated with alpha and beta blockade.
Rates of glucose uptake remained 20% below those observed with saline
alone, p<0.001. A significant inverse correlation was observed
between the height of the blood pressure and the rate of glucose
uptake r=0.32, p=0.04. In conclusion, acute induction of hypertension
with L-NMMA can cause marked insulin resistance. We postulate that
reduced skeletal muscle perfusion and/or sympathetic nervous system
activation may contribute to insulin resistance induced by L-NMMA.
Received 9 September 1994; accepted in final form 19 April 1995.
APS Manuscript Number E370-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 2 May 1995.