1. The present study was designed to explore the role of NO derived from l-arginine in the vasodilatory response to synthetic human parathyroid hormone-related peptide-(1–34) in the isolated rabbit kidney perfused in the presence of indomethacin (10 μmol/l) and preconstricted with noradrenaline (7.2 nmol/min).
2. Under control conditions, bolus administrations of acetylcholine (10 μmol/l), an NO-dependent renal vasodilator, verapamil (0.1 mmol/l), an NO-independent renal vasodilator, and parathyroid hormone-related peptide (87 nmol/l) decreased the preconstriction pressure, by 31%, 71% and 43%, respectively.
3. Bolus administration of 100 μmol/l NG-nitro-l-arginine-methyl ester caused a 20% increment in the perfusion pressure of the noradrenaline-preconstricted kidney. NG-nitro-l-arginine methyl ester inhibited the vasodilatory effect of acetylcholine and parathyroid hormone-related peptide, by 68% and 44%, respectively, but did not alter the verapamil-induced vasodilatation.
4. Unlike l-arginine, the bolus administration of 1 μmol/l of a mono-substituted l-arginine derivative, N-α-benzoyl-l-arginine ethyl ester, durably decreased the noradrenaline/NG-nitro-l-arginine methyl ester-induced preconstriction by 57%.
5. Both l-arginine and N-α-benzoyl-l-arginine ethyl ester effectively reversed the inhibition induced by NG-nitro-l-arginine methyl ester on the vasodilatation elicited by acetylcholine and parathyroid hormone-related peptide.
6. In conclusion, the formation of NO from l-arginine contributes a substantial part to the vasodilatory action of parathyroid hormone-related peptide. Therefore, parathyroid hormone-related peptide appears to have a place among the renal haemodynamically active substances, whose vasodilatory actions are tuned by NO.