Hypercapnia-induced contraction in isolated pulmonary arteries is endothelium-dependent.
It has been demonstrated previously that isohydric hypercapnia (IH) does not affect agonist-induced tension development in pulmonary arteries. The aim of the present study was to examine the effects of IH on depolarisation-induced, steady state tension in the isolated rat pulmonary artery. Rings were submaximally contracted with high KCl under control conditions (5% CO(2)-95% air). IH was achieved by switching to a modified PSS (isosmotic substitution of NaHCO(3) for NaCl), equilibrated with 10% CO(2) in air. On switching to IH, a significant increase in mean (+/-SEM) tension (25.3+/-6.3% Tmax) was observed in endothelium intact rings (n=6). Endothelial removal significantly reduced this response. Non-specific inhibition of nitric oxide synthase (NOS) isoenzymes (L-NAME, 10(-3) M) abolished the IH-induced increase in tension while inhibition of neuronal NOS (TRIM, 10(-5) M) was without effect. The relaxant response to the nitric oxide donor sodium nitroprusside was similar in IH and control conditions. These results suggest that IH caused an endothelium-dependent increase in depolarisation-induced tension by reducing NO production.
Lynch
F
F
Department of Human Anatomy and Physiology, University College Dublin, Earlsfort Terrace, 2, Dublin, Ireland.
Sweeney
M
M
O'Regan
R G
RG
McLoughlin
P
P
D000109:Acetylcholine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology*; D006935:Hypercapnia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000316:Adrenergic alpha-Agonists; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D010656:Phenylephrine; D000109:Acetylcholine