Insulin-induced hypertension, L-arginine, and endothelial nitric oxide synthase in pregnant rats

Pregnancy-induced hypertension in rats with chronic exogenous hyperinsulinemia is associated with reduced urinary excretion of nitric oxide metabolites. We tested the hypothesis that there are perturbations of endothelial nitric oxide synthase in their kidneys. We studied three groups of rats: control pregnant rats (n = 6); pregnant rats with hyperinsulinemia by subcutaneous sustained-release insulin pellet (n = 5); and hyperinsulinemic pregnant rats treated with L-arginine 2 gL in drinking water (n = 5). By the end of pregnancy blood pressure was 78 +/- 12 mm Hg in controls, 119 15 mm Hg in hyperinsulinemic rats, and 77 +/- 8 mm Hg in L-arginine-treated hyperinsulinemic rats, p < 0.007. Serum creatinine was 0.4 mg/dl in controls, 0.6 mg/dl in hyperinsulinemic rats, and 0.5 mg/dl in L-arginine-treated rats, p < 0.05. Corresponding urinary excretion of nitric oxide metabolites was 2.1 +/- 0.5, 1.2 +/- 0.2, and 1.5 +/- 0.2 mumols/mg creatinine, p < 0.01. Expression of endothelial nitric oxide synthase protein in kidneys by Western blot was not different between controls and hyperinsulinemic rats, 5.6 +/- 2.4 and 5.8 +/- 3.4 OD x mm(2), but was nearly doubled in L-arginine-treated rats, 10.8 +/- 2.3, p < 0.03. Thus, the salutary effect of L-arginine on hyperinsulinemic pregnancy-induced hypertension (PIH) may be mediated, in part, by endothelial nitric oxide synthase in their kidneys.