Mechanosensitive release of parathyroid hormone-related peptide from coronary endothelial cells.
10.1152/ajpheart.00925. 2001.-Parathyroid hormone-related peptide (PTHrP) is expressed throughout the cardiovascular system and is able to dilate vessels. This study investigated whether mechanical forces generated by changes in regional perfusion influence PTHrP release from the coronary vascular bed. Experiments were performed in vitro on saline-perfused rat hearts or isolated coronary endothelial cells exposed to cyclic strain and in vivo in anesthetized pigs. In vitro, PTHrP release from saline-perfused rat hearts was strongly correlated with coronary flow (r = 0.84). Increasing coronary flow from 5 to 10 ml/min increased PTHrP release from 442 +/- 42 to 1,563 +/- 167 pg/min. Increasing the viscosity of the perfusate did not change basal PTHrP release. Increasing flow without a concomitant increase in pressure did not lead to an increase in release rate, but reduction in pressure under flow-constant conditions reduced PTHrP release rate. Cyclic strain induced a strain-dependent release of PTHrP from endothelial cells that was inhibited by the addition of a calcium-chelating agent. In vivo, there was a net release of PTHrP in the coronary circulation and decreases in coronary flow and pressure decreased the PTHrP release rate. Bradykinin in the presence of constant pressure increased PTHrP release, probably by increasing the intracellular calcium concentration in coronary endothelial cells. In summary, mechanical forces evoked by blood flow can trigger a constant PTHrP release.
Degenhardt
Heike
H
Physiologisches Institut, Justus-Liebig-Universität, D-35392 Giessen, Germany.
Jansen
Johanna
J
Schulz
Rainer
R
Sedding
Daniel
D
Braun-Dullaeus
Ruediger
R
Schlüter
Klaus-Dieter
KD
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D003331:Coronary Vessels / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D009589:Nitrogen Oxides; D044162:Parathyroid Hormone-Related Protein; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D012965:Sodium Chloride; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013314:Stress, Mechanical; D013556:Swine, Miniature; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; C091861:spermine nitric oxide complex; D010656:Phenylephrine; D019335:Nitroarginine; D013096:Spermine; D009569:Nitric Oxide; D012965:Sodium Chloride; D001120:Arginine; D001920:Bradykinin