Functional comparison of endothelin receptors in human and rat pulmonary artery smooth muscle.
The receptors mediating arterial smooth muscle contraction to endothelins (ET) differ among species and origin of vascular bed. We characterized ET receptors mediating contraction of endothelium-denuded human intralobar pulmonary artery (hIPA) and rat intralobar (rIPA) and extralobar left branch (rLPA) pulmonary artery with ET-1, ET-2, ET-3, sarafotoxin S6c, sarafotoxin S6b, and ET receptor antagonists in vitro. Rat aorta was studied for comparison. Each vascular segment showed concentration-dependent contraction with a rank order sensitivity (pD2) profile of ET-1 > or = ET-2 = sarafotoxin S6b > ET-3. Maximum contraction to ET-1 was greater than to sarafotoxin S6c in all preparations. Responses of rIPA and rLPA to sarafotoxin S6c were conspicuous when compared with hIPA or aorta. The ET(A) receptor blockers BQ-123 and BMS-182874 competitively antagonized ET-1 responses of hIPA and aorta, but not rLPA. The ET(B) receptor antagonist BQ-788 attenuated contractions of rIPA and rLPA to ET-3 and sarafotoxin S6c, respectively. In conclusion, ET(B)-mediated contraction of endothelium-denuded conduit pulmonary arteries varies among species and may contribute more to contraction of rIPA and rLPA than of hIPA and aorta, although maximum ET(B)-mediated contraction is smaller than that mediated by the ET(A) receptor.
Bialecki
R A
RA
Respiratory, Inflammatory, and Neurological Diseases Research Section, ZENECA Pharmaceuticals, Wilmington, Delaware 19850-5437, USA.
Fisher
C S
CS
Murdoch
W W
WW
Barthlow
H G
HG
Bertelsen
D L
DL
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D003619:Dansyl Compounds / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism*; D051381:Rats / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism*
D003619:Dansyl Compounds; D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D017466:Receptors, Endothelin; C085754:5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)