Overall Hemodynamic Studies After the Chronic Inhibition of Endothelial-Derived Nitric Oxide in Rats

Previous studies have demonstrated that an acute intravenous administration of nitro- -arginine methyl ester (L-NAME) causes a sustained hypertension and widespread vasoconstriction. However, little information is available regarding the chronic effect of L-NAME on circulatory hemodynamics. Therefore, the purpose of the present study was to characterize both the systemic and regional hemodynamics after the chronic inhibition of endothelium-derived nitric oxide in male Sprague Dawley rats. The rats were divided into two groups: control (n = 8) and L-NAME (n = 8). The rats in the control group received only tap water and the rats in the L-NAME group received oral L-NAME solution at a dose of 0.1 mg/mL in the drinking water ad libitum. Four weeks after L-NAME or tap water treatment the rats were anesthetized with inactin, and mean arterial blood pressure, cardiac output, and individual organ flows were measured. Cardiac output and individual organ flows were measured using radioactive microspheres. Chronic administration of L-NAME resulted in a significant increase in mean arterial blood pressure from a control value of 118 ± 4 mm Hg to 174 ± 8 mm Hg (P< .01). Cardiac output decreased from a control value of 29 ± 2 mL/min/100 g to 20 ± 2 mL/min/100 g (P< .01) and total peripheral resistance increased from a control value of 4.3 ± 0.3 mm Hg/mL/min/100 g to 9.7 ± 1.4 mm Hg/mL/min/100 g (P< .01). In addition, chronic L-NAME treatment resulted in a widespread vasoconstriction and decrease in regional blood flows. Kidney flow in L-NAME-treated rats decreased from a control value of 5.5 ± 0.4 mL/min/g to 3.0 ± 0.3 mL/min/g (P< .01). Also liver, spleen, stomach, large intestine, and testicular flows decreased significantly. These results indicate that endothelium-derived nitric oxide is an important modulator in long-term regulation of arterial blood pressure and blood flows to individual tissues