Inhibition of synthesis of endothelium-derived nitric oxide in conscious dogs. Hemodynamic, renal, and hormonal effects.

The role of endothelium-derived nitric oxide (EDRF/NO) for control of systemic and regional vascular resistances and for regulation of neurohumoral systems was investigated by studying the effects of the inhibitor of EDRF/NO-synthesis NG-nitro-L-arginine (L-NNA; 5 mg/kg) in six conscious dogs. L-NNA increased mean arterial pressure by an increase in total peripheral resistance, increased renal vascular, and total pulmonary resistances and reflexly decreased heart rate and cardiac output. Renal plasma flow, urine flow, and urinary sodium excretion were reduced, glomerular filtration rate was not affected. These changes were reversed by additional treatment with L-arginine (150 mg/kg). Plasma concentrations of renin, norepinephrine, vasopressin, and atrial natriuretic peptide were not changed by L-NNA. Our conclusions were that basal release of EDRF/NO plays an important physiologic role for control of systemic and regional vascular resistances, thereby controlling blood pressure, organ blood flow, and function. Neurohumoral systems are not affected by the inhibition of EDRF/NO synthesis and do not contribute to the observed vasoconstriction.