Endogenous nitric oxide as a probable modulator of pulmonary circulation and hypoxic pressor response in vivo.
The objective of this study was to investigate the role of endogenous nitric oxide, formed from L-arginine, in the regulation of pulmonary circulation in vivo, with special reference to the hypoxic pressor response. In artificially ventilated open-chest rabbits, pulmonary vascular resistance at normoxic ventilation (FIO2 = 21%) was 78 +/- 16 cmH2O ml-1 min 1000-1 (mRUL). Hypoxic ventilation (FIO2 = 10%) increased pulmonary vascular resistance to 117 +/- 17 mRUL. N omega-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased pulmonary vascular resistance at normoxic ventilation to 192 +/- 28 mRUL and during hypoxic ventilation to 462 +/- 80 mRUL. During N omega-nitro-L-arginine methylester infusion there was also an increase in mean arterial blood pressure as well as a decrease in cardiac output that was even more pronounced during hypoxic ventilation. L-arginine reversed the effect of N omega-nitro-L-arginine methylester on pulmonary vascular resistance at normoxic ventilation to 140 +/- 26 mRUL and at hypoxic ventilation to 239 +/- 42 mRUL. In spontaneously breathing closed-chest rabbits, N omega-nitro-L-arginine methylester evoked a marked decrease in arterial PO2 and increases in respiration frequency and central venous pressure, while blood pH, PCO2 and base excess remained unchanged. Taken together these findings indicate that endogenous nitric oxide, formed from L-arginine, might be a regulator of ventilation-perfusion matching at normoxic ventilation, and that nitric oxide acts as an endogenous modulator of the hypoxic pressor response.
Persson
M G
MG
Department of Physiology, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden.
Gustafsson
L E
LE
Wiklund
N P
NP
Moncada
S
S
Hedqvist
P
P
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D019001:Nitric Oxide Synthase; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects / Q000502:physiology
D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester