Luminal ATP-induced contraction of rabbit pulmonary arteries and role of purinoceptors in the regulation of pulmonary arterial pressure.
The effects of luminal ATP between rabbit pulmonary (PAs) and coronary arteries (CAs) were compared to understand the role of purinoceptors in the regulation of pulmonary arterial pressure (PAP) under hypoxia. Diameters of vessels were video analyzed under luminal perfusion. ATP-induced membrane currents and intracellular Ca(2+) signals ([Ca(2+)](i)) were compared in pulmonary (PASMCs) and coronary myocytes (CASMCs) using patch clamp and spectrofluorimetry. PAP was measured in perfused lungs under ventilation. Luminal ATP induced constriction of rabbit PAs in the presence of endothelium. In contrast, CAs showed dilating responses to luminal ATP even in the absence of endothelium. In PASMCs, both P2X-mediated inward current and P2Y-mediated store Ca(2+) release were consistently observed. In contrast, CASMCs showed neither P2X nor P2Y responses. In the perfused lungs, hypoxia-induced PAP increase was decreased by suramin, a purinergic antagonist. A luminal application of alpha,beta-meATP largely increased PAP, whereas UTP decreased PAP. The combined application of P2X- and P2Y-selective agonists (alpha,beta-meATP and UTP) increased PAP. However, the perfusion of ATP alone decreased PAP, and the ATP-induced PAP decrease was affected neither by adenosine receptor antagonist nor by nitric oxide synthase inhibitor. In summary, although the luminal ATP constricts isolated PAs and suramin attenuated the HPV of perfused lungs, the bimodal responses of PAP to purinergic agonists indicate that the luminal ATP regulates pulmonary circulation via complex signaling interactions in situ.
Baek
Eun Bok
EB
Department of Physiology, Seoul National University College of Medicine, Seoul, 110-799, Republic of Korea.
Yoo
Hae Young
HY
Park
Su Jung
SJ
Kim
Hyang Sun
HS
Kim
Seong Deok
SD
Earm
Yung E
YE
Kim
Sung Joan
SJ
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D020013:Calcium Signaling; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010477:Perfusion; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects; D011817:Rabbits; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism*; D012121:Respiration, Artificial; D013050:Spectrometry, Fluorescence; D013498:Suramin / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation; D014741:Video Recording
D018048:Receptors, Purinergic P2; C022571:adenosine 5'-O-(3-thiotriphosphate); C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D013498:Suramin; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D014544:Uridine Triphosphate