The vasodilator action of parathyroid hormone fragments on isolated perfused rat kidney.
The renal vasodilator responses to various fragments of PTH were quantified on a model of isolated perfused rat kidney (IPK), under non-filtering conditions. The 1-34 fragment of bovine PTH, its Nle analogue and rat PTH, injected in sequential cumulative doses, caused concentration-dependent vasodilatation in the vasculature of the IPK which was preconstricted with prostaglandin F2 alpha. The EC50 of PTH for renal vasodilatation ranged from 1 to 2 nM for all PTH fragments and maximum vasodilatation ranged from 33 to 41% of the maximum vasodilatation induced by papaverine. Renal vasodilation was not related to prostaglandin release since similar vasodilatation occurred after the inhibition of prostaglandin synthesis with indomethacin. When PTH was administered in single bolus injections, using a separate kidney for each hormone concentration, rather than repeated injections into the same kidney, higher maximum vasodilatations were obtained (64%). These results most likely reflected tachyphylaxis of the renal vasculature to PTH occurring after repeated exposure of a single kidney to the hormone. The antagonist analogue [Nle8,18, Tyr34]-bPTH-(3-34)A shifted the concentration-related response curve to the right, indicating that the renal vasodilator response to rPTH-(1-34) involved specific vascular receptors.
Musso
M J
MJ
Institut de Pharmacologie et de Médicine Expérimentale (URA DO 589 CNRS), Strasbourg, France.
Barthelmebs
M
M
Imbs
J L
JL
Plante
M
M
Bollack
C
C
Helwig
J J
JJ
D000818:Animals; D015237:Dinoprost / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D019379:Teriparatide; D014665:Vasodilator Agents
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D014665:Vasodilator Agents; D019379:Teriparatide; C031617:parathyroid hormone (3-34); D015237:Dinoprost