CHRONIC EXOGENOUS HYPERINSULINEMIA IN PREGNANCY - A RAT MODEL OF PREGNANCY-INDUCED HYPERTENSION

Insulin resistance and hyperinsulinemia are associated with essential hypertension. There is also evidence of hyperinsulinemia in women who developed hypertension in pregnancy (P). The present study examines wh ether chronic hyperinsulinemia in pregnant rats plays a role in the de velopment of hypertension in pregnancy. A sustained-release insulin pe llet was implanted subcutaneously in 15 Wistar rats (P-INS) 1 wk befor e and on day 7 of pregnancy; 14 control rats were sham-implanted (P-SH AM). Tail-cuff systolic BP (SBP), serum triglycerides, glucose, insuli n, renal function, and urinary excretion of Naf and of metabolites of nitric oxide were determined throughout pregnancy. Data were analyzed by ANOVA with basal body weight as covariate analysis of covariance. R esults are expressed as the mean +/- SD. Body weight; water and food i ntake; urine volume; creatinine clearance; and level of proteinuria at the end of pregnancy were similar in both groups. The number of fetus es was 9 +/- 2.3 in P-INS versus 11 +/- 2.4 in pregnant control rats ( P < 0.05). Before mating, SBP was similar, but at the end of pregnancy SBP was 110 +/- 18 mmHg in P-INS versus 85 +/- 12 mmHg in pregnant ra ts (P < 0.05). Serum triglycerides and Na+ were also higher in P-INS r ats. The fractional excretion of Na+ was 3.1 +/- 1.0 versus 4.4 +/- 1. 5, respectively (P < 0.01). The percent increase in nitric oxide metab olite excretion was 233 +/- 14 versus 370 +/- 17%, respectively (P < 0 .01). Chronic hyperinsulinemia, without sugar supplementation, and hyp ertriglyceridemia may cause a decrease in the synthesis of nitric oxid e in P-WS rats. The development of hypertension in these rats may be a ssociated with an impaired vasodilatation, together with an increased renal sodium reabsorption.