Systemic Hemodynamics and Regional Blood Flow During Chronic Nitric Oxide Synthesis Inhibition in Pregnant Rats

Pregnancy-induced hypertension in women is associated with severe vasoconstriction and reductions in organ blood flow and cardiac output. Recent studies have indicated that nitric oxide (NO) synthesis inhibition during mid to late gestation in pregnant rats results in severe hypertension and proteinuria. The purpose of this study was to determine the systemic hemodynamic and regional blood flow alterations associated with chronic NO synthesis inhibition in the pregnant rat. The study was conducted in four groups of rats: virgin rats (n=6), pregnant rats (n=10), virgin rats treated with l-NAME (n=6), and pregnant rats treated with l-NAME (n=11). Rats were treated with l-NAME in drinking water at a dose of 1 mg/d for a week starting from day 13 of gestation in pregnant rats or an equivalent time for virgins. Mean arterial pressure (MAP), cardiac output, total peripheral resistance (TPR), and regional flows were measured by tracing radiolabeled microspheres in conscious rats. Pregnant rats that were given l-NAME showed significantly higher MAP (137±6 versus 96±2 mm Hg), higher TPR (5.08±0.58 versus 2.90±0.44 mm Hg/mL/min/100 g), and lower cardiac output (87.4±8.4 versus 113.3±11.1 mL/min) than pregnant controls. Chronic NO synthesis inhibition decreased the renal blood flow in pregnant rats at a significantly greater magnitude than in virgin rats. Significant reductions in regional blood flow to the heart, lungs, liver, diaphragm, and skeletal muscles were also observed in pregnant rats treated with l-NAME. The results of this study indicate that NO may play a role in mediating the alterations in systemic hemodynamics and regional blood flow in late pregnant rats.