Involvement of nitric oxide in the vasodilatory response to parathyroid hormone-related peptide in the isolated rabbit kidney.
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 mumol/l) and preconstricted with noradrenaline (7.2 nmol/min). 2. 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. 3. 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. 4. 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%. 5. 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. 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.
Simeoni
U
U
Laboratoire de Physiologie Cellulaire Rénale, Université Louis Pasteur (DRED AL67u20), Strasbourg, France.
Massfelder
T
T
Saussine
C
C
Judes
C
C
Geisert
J
J
Helwig
J J
JJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D007668:Kidney / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010477:Perfusion; D011506:Proteins / Q000494:pharmacology*; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D009569:Nitric Oxide; D001120:Arginine; D014700:Verapamil; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester