The cGMP pathway is not responsible for the blunted hypoxic vasoconstriction in rat lungs after altitude exposure.
To examine the contribution of the cyclic guanosine monophosphate (cGMP) pathway in changes in pulmonary vasoconstriction during the initial days of altitude exposure, we tested the effects of LY83583 (an inhibitor of guanylate cyclase activation) and those of N(G)-monomethyl-L-arginine (an inhibitor of nitric oxide synthesis) on airway hypoxia- (3% O2) and angiotensin II- (AII, 0.2 microg) induced vasoconstrictions in lungs from the rats exposed to either moderate altitude (MA, 570 torr) or high altitude (HA, 430 torr) At 2 days' exposure, hypoxic response was significantly blunted compared with the response in low-altitude (LA, 710 torr) lungs in an altitude-dependent manner. At 7 days' exposure, the response was recovered fully in MA lungs but partially in HA lungs. AII response was not significantly blunted at 2 days' exposure, but was significantly augmented in an altitude-dependent manner at 7 days' exposure. LY83583 (10 micromol L(-1)) potentiated both responses in LA lungs but did not significantly potentiate either response in any altitude-exposed lungs. N(G)-monomethyl-L-arginine (10 micromol L(-1)) potentiated both responses in LA lungs but did not significantly potentiate either response in HA lungs at 2 days' and 7 days' exposure. Thus the cGMP pathway is not responsible for either the change in hypoxic vasoconstriction or the change in AII vasoconstriction in rat lungs during the initial 7 days of altitude exposure.
Asano
K
K
Research Centre for Aging and Adaptation, Shinshu University School of Medicine, Matsumoto, Japan.
Yanagidaira
Y
Y
Yoshimura
K
K
Sakai
A
A
D000531:Altitude; D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP