[Inhibition of endogenous nitric oxide synthesis enhances acute hypoxic pulmonary vasoconstriction].
The objective of this study was to observe the role of endogenous nitric oxide, formed from L-arginine, in the regulation of acute hypoxic pulmonary vasoconstriction by inhibiting its synthesis with the false substrate NG-nitro-L-arginine methyl ester (L-NAME) in anesthetized dogs. L-NAME (1 mg/kg, 5 mg/kg, 15 mg/kg) significantly increased the mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) during hypoxic ventilation (FiO2 = 0.10) and its action lasted for 90-180 minutes. The maximum increase value (MIV) of hypoxic mPAP in three groups (4 dogs each group) is 1.1 +/- 0.2, 1.5 +/- 0.3, 1.6 +/- 0.4 kPa (1 kPa = 7.5 mmHg), respectively, while that of hypoxic PVR is 58.4 +/- 15.6, 99.3 +/- 28.8, 78 +/- 4.0 kPa.s/L (all P < 0.05 vs hypoxic control before the injection). The increase percent of hypoxic mPAP and PVR induced by L-NAME (15 mg/kg) was 45.23 +/- 5.78% and 133.2 +/- 35.22% 30 minutes after the injection, which was more remarkable than that of mPAP and PVR (18.83 +/- 5.63%, 84.13 +/- 22.67%, respectively) by L-NAME (1 mg/kg). L-arginine (0.5 g/kg) reversed the effect of L-NAME (5 mg/kg) on mPAP and PVR at hypoxic ventilation within one hour. L-NAME also markedly increased hypoxic mean arterial blood pressure at the dose of 15 mg/kg (MIV 2.7 +/- 0.7 kPa) and systemic vascular resistance at the three separate doses (MIV 354.4 +/- 99.7, 456.2 +/- 105, 361.5 +/- 70 kPa x s/L, respectively), meanwhile it remarkably decreased cardiac output and heart rate during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pulmonary Medicine, PUMC Hospital, Beijing.
W B
WB
Cao
Y J
YJ
Zhu
W C
WC
Luo
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D011651:Pulmonary Artery / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester