Changes in Renal and Systemic Hemodynamics after NO-Synthase Inhibition in Males with Family History of Hypertension

Abstract

Background: Nitric oxide (NO) plays an important role in the regulation of blood pressure and renal hemodynamics. Methods: To further investigate the role of NO in human hypertension, we studied the effect of systemic injection of N^G-monomethyl- L-arginine (L-NMMA) on renal hemodynamics, urinary sodium excretion (FE_Na), systemic hemodynamics and several vasoactive hormones in 5 healthy male subjects with (group H) and without (group N) family history of hypertension. An intravenous infusion of L-NMMA (3 mg/kg over 10 min) or placebo was given in a randomized, double-blinded manner. GFR and ERPF were measured by inulin- and PAH-clearances. Norepinephrine infusion (0.1 µg/kg/min over 60 min) served as vasoconstrictive control infusion. Results: L-NMMA induced a significant decrease in ERPF (–135 ± 49 vs. 7 ± 31 ml/min/1.73 m² with placebo, p < 0.05), a decrease in FE_Na (–1.2 ± 0.6% with L-NMMA vs. 0.0 ± 0.1% with placebo), and a significant increase in diastolic blood pressure (+7 ± 1 vs. –2 ± 1 mm Hg with placebo) in group N, only. A sustained drop in plasma renin activity (–0.1 ± 0.1 vs. 0.3 ± 0.1 ng/ml/h with placebo) could also be seen in this group, only. Subjects with family history of hypertension showed minor or even no response (changes in diastolic blood pressure: L-NMMA: 5 ± 3 mm Hg, placebo: 0 ± 2 mm Hg; changes in ERPF: L-NMMA: –89 ± 57 ml/min/1.73 m², placebo: –34 ± 28 ml/min/1.73 m²; changes in plasma renin activity: L-NMMA: –0.0 ± 0.3 ng/ml/h, placebo: –0.1 ± 0.2 ng/ml/h). The vasoconstrictive effect of norepinephrine infusion did not differ between both groups. Conclusion: Our data indicate that systemic NO synthetase inhibition by L-NMMA results in a blunted effect on systemic blood pressure and the renal hemodynamic system in subjects with family history of hypertension.