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 mumol/l) and preconstricted with noradrenaline (7.2 nmol/min).
Under control conditions, bolus administrations of acetylcholine (10 mumol/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.
Bolus administration of 100 mumol/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.
Unlike L-arginine, the bolus administration of 1 mumol/l of a mono-substituted L-arginine derivative, N-alpha-benzoyl-L-arginine ethyl ester, durable decreased the noradrenaline/NG-nitro-L-arginine methyl ester-induced preconstriction by 57%.
Both L-arginine and N-alpha-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.
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.