Subpressor dose of L-NAME unmasks hypertensive effect of chronic hyperinsulinemia

We previously found that chronic exogenous hyperinsulinemia without sugar s upplementation does not elevate blood pressure. This may be partially expla ined by the ability of insulin to release nitric oxide and cause vasodilata tion. To test this hypothesis, we studied 4 groups of rats: 9 rats (body we ight, 213+/-14 g) treated with a gradual increase of a sustained-release su bcutaneous insulin pellet; 9 rats (body weight, 213+/-9 g) treated with N-G -nitro-L-arginine methyl ester(L-NAME) in drinking water 50 mg/L; 19 rats ( body weight, 217+/-11 g) treated with the combination of L-NAME and insulin ; and 9 control rats (body weight, 218+/-11 g). Blood pressure was followed weekly for 6 weeks, and then rats were studied in metabolic cages. Weight gain was not different during the 6 weeks. Renal function did not differ be tween the 4 groups, but 24-hour urinary nitrite/nitrate excretion was lower (P<0.02) in L-NAME-treated and higher in insulin-treated rats. Plasma insu lin doubled (P<0.002) in the insulin-treated rats, but there was no hypogly cemia and, by week 6, fructosamine levels were 2.1+/-0.2, 2.1+/-0.2, 2.3+/- 0.1, and 2.3+/-0.2 mmol/L in control rats and rats treated with L-NAME, ins ulin, and L-NAME plus insulin, respectively. Systolic blood pressure, which did not differ at baseline, at week 3 was 122+/-17, 118+/-17, and 118+/-24 mm Hg in the control, L-NAME, and insulin groups and 136+/-14 mm Hg (P<0.0 3) in the combination group. At week 6, systolic blood pressure was 128+/-1 4, 127+/-15, and 118+/-13 mm Hg in the control, L-NAME, and insulin groups, respectively, and 150+/-14 mm Hg (P<0.0005) in the combination group. In a subsequent experiment, L-arginine 2 g/L abrogated the effects of L-NAME an d insulin combination. In conclusion, chronic exogenous hyperinsulinemia do es not affect blood pressure but may cause hypertension when endothelial fu nction is compromised.