L-ARGININE DOES NOT PREVENT THE RENAL EFFECTS OF ENDOTHELIN IN HUMANS

The infusion of endothelin to obtain plasma levels as present in sodiu m-retaining conditions such as heart failure and hepatorenal syndrome has been shown to cause sodium retention and renal vasoconstriction. W hether these renal effects of endothelin could be modulated by the sti mulation of nitric oxide production by the infusion of L-arginine was examined. Therefore, the renal and endocrine effects of the systemic a dministration of endothelin (2.5 ng/kg per minute for 90 min), L-argin ine (5 mg/kg per minute for 90 min), or the combination of endothelin and L-arginine were studied in healthy subjects under clearance condit ions, During endothelin infusion, plasma endothelin levels rose from 3 .0 +/- 0.2 to 14.1 +/- 2.4 pmol/L (P < 0.01). Mean arterial pressure i ncreased by 7 mm Hg (P < 0.01). The effects on renal function were dis proportionately large: renal vascular resistance increased from 77.5 /- 3.2 to 124.1 +/- 6.7 mm Hg/min per liter (P < 0.01), and sodium exc retion fell from 178 +/- 30 to 83 +/- 11 mu mol/min (P < 0.01). Endoth elin had no effect on urinary nitrite excretion. L-Arginine caused a f all in blood pressure of 5 mm Hg (P < 0.01) and decreased renal vascul ar resistance by 12% (P < 0.05). Sodium excretion increased twofold, T his was associated with an increase in urinary nitrite excretion from 112 +/- 36 to 465 +/- 190 nmol/min (P < 0.01), suggesting stimulation of renal nitric oxide production. During the combination of endothelin and L-arginine, urinary nitrite excretion increased similarly. L-Argi nine prevented the effects of endothelin on blood pressure, and in fac t, blood pressure de creased by 4 mm Hg during the combination of endo thelin and L-arginine (P < 0.01). However, L-arginine could not preven t the renal vasoconstrictive and sodium-retaining effects of endotheli n. These findings suggest that the role of nitric oxide as a physiolog ic antagonist of renal vasoconstriction is limited.