N-terminal parathyroid hormone-related peptide hyperpolarizes endothelial cells and causes a reduction of the coronary resistance of the rat heart via endothelial hyperpolarization.
Parathyroid hormone-related peptide (PTHrP) is known to be a strong vasorelaxant peptide. The mechanisms by which PTHrP reduces the coronary resistance of the rat heart have not been worked out but seem to be independent of the classical PTH/PTHrP receptor-mediated, cAMP-dependent effect. In this study we hypothesized that PTHrP reduces the coronary resistance of the rat heart via endothelial cell hyperpolarization. Isolated microvascular endothelial cells from rat heart were incubated with PTHrP(1-36), and changes in the membrane potential were recorded via DiBAC fluorescence. Cells exposed to PTHrP showed a hyperpolarization of approximately 7mV. In the isolated Langendorff preparation, PTHrP-dependent vasodilatation of l-nitro-arginine-exposed hearts was abolished under depolarizing conditions (high potassium). Denudation of the endothelial cell layer significantly impaired the vasodilatory effect of PTHrP. In the presence of H89 (a cAMP/protein kinase A pathway antagonist) and indomethacin (a cyclooxygenase inhibitor), PTHrP dilated the vessels. In conclusion, PTHrP exerted a nitric oxide-independent vasodilatory effect that depends on endothelial cell hyperpolarization.
Abdallah
Yaser
Y
Justus-Liebig-Universität Giessen, Physiologisches Institut, Aulweg 129, D-35392 Giessen, Germany.
Ross
Günter
G
Dolf
Alexandra
A
Heinemann
Marcus P
MP
Schlüter
Klaus-Dieter
KD
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D009924:Organ Culture Techniques; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects
D044162:Parathyroid Hormone-Related Protein; D047428:Protein Kinase Inhibitors; D017868:Cyclic AMP-Dependent Protein Kinases