Endothelium-dependent relaxation and cyclic GMP accumulation in rabbit pulmonary artery are selectively impaired by moderate hypoxia.
The effect of hypoxia on endothelium-dependent and endothelium-independent vasodilation was studied in phenylephrine-precontracted, isolated rings of rabbit first-branch pulmonary artery. Concentration-dependent relaxation responses to the endothelium-dependent dilators methacholine, ATP, and the calcium ionophore (A23187) as well as to the endothelium-independent dilators sodium nitroprusside and isoproterenol were obtained before, during, and after exposure to hypoxia (PO2 = 42 +/- 1 mm Hg) in the presence of indomethacin (2.8 x 10(-5) M). This moderate degree of hypoxia inhibited (p less than 0.05) endothelium-dependent but not endothelium-independent relaxation responses without producing irreversible vascular damage. In parallel experiments, cyclic GMP accumulation in pulmonary vascular rings in response to maximal doses of the above vasodilators was measured in the presence and absence of hypoxia. Cyclic GMP accumulation in response to endothelium-dependent dilators (methacholine, ATP, and A23187) was inhibited (p less than 0.05) by hypoxia while cyclic GMP accumulation in response to the endothelium-independent dilator sodium nitroprusside was not. When phenylephrine precontracted vessels were exposed to hypoxia in the absence of vasodilators, a small, transient increase in tension occurred, which was greater in endothelium-intact than in endothelium-denuded vessels (0.70 +/- 0.12 vs. 0.09 +/- 0.03 g, respectively; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Johns
R A
RA
Department of Anesthesiology, University of Virginia School of Medicine, Charlottesville.
Linden
J M
JM
Peach
M J
MJ
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D011651:Pulmonary Artery / Q000502:physiology*; D011817:Rabbits; D011983:Receptors, Purinergic / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D008688:Methacholine Compounds; D011983:Receptors, Purinergic; D016210:Methacholine Chloride; D009599:Nitroprusside; D009569:Nitric Oxide; D000001:Calcimycin; D000255:Adenosine Triphosphate; D006152:Cyclic GMP; D007545:Isoproterenol