Nitric oxide modulates renal vasoconstrictor effect of endothelin-1 in conscious lambs.

To test the hypothesis that nitric oxide (NO) buffers the renal vasoconstrictor effects of endothelin-1 (ET-1) early in life, renal haemodynamic responses to ET-1 were measured in the presence and absence of endogenously produced NO in conscious lambs. Renal haemodynamic effects of ET-1 were measured for 5 min before (control) and 20 min after intraarterial injection of ET-1 before and after pretreatment with 20 mg/kg of the L-arginine analogue N(G)-nitro-L-arginine methyl ester (L-NAME), (experiment 1) and its inactive isomer D-NAME (experiment 2) in conscious lambs aged approximately 1 week (N=7) and approximately 6 weeks (N=6). The two experiments were carried out in random order at intervals of 24-48 h. In lambs aged approximately 6 weeks, a marked increase in renal vascular resistance (RVR) was elicited by ET-1 administration; this response was enhanced twofold following pretreatment with L-NAME. In 1-week-old lambs, however, an increase in RVR in response to ET-1 occurred only after pretreatment with L-NAME. Therefore, we accept our hypothesis and conclude that NO buffers the renal vasoconstrictor effects of ET-1 early in life.