Effect of BTS 49465 on hypoxic pulmonary vasoconstriction.
The effect of BTS 49465 on hypoxic pulmonary vasoconstriction was compared with placebo and sodium nitroprusside in 10 spontaneously breathing anesthetized mongrel dogs. Vascular pressures, cardiac output, and arterial blood gases were monitored on 2 study days (greater than 1 week apart) during which, after baseline measurements on room air, the pulmonary pressor response to alveolar hypoxia (12% O2) and the effect of sodium nitroprusside (10 micrograms/kg/min) were assessed. The animals then inspired room air and, after the pressures had returned to baseline, either BTS 49465 (10 mg/kg, i.v.) or an equal volume of placebo was administered. The animals were monitored for the next 3.5 h. Although the room air and initial hypoxic (PaO2 = 50 +/- 1.5 torr) measurements were similar in both studies, 1 h after BTS 49465 was administered there was a significant reduction in pulmonary artery pressure (21.6 +/- 1.3 versus 27.6 +/- 1.8 torr, p less than 0.05), which was maintained throughout the 3.5 h study period. There was also a small increase in cardiac index from 4.1 +/- 0.4 to 4.6 +/- 0.2 L/min/m2 after BTS 49465 which was not statistically significant. Quantitatively the effects of BTS 49465 and sodium nitroprusside were similar. We conclude that BTS 49465 is an effective pulmonary vasodilator that ameliorates hypoxic vasoconstriction.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010100:Oxygen / Q000097:blood / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects*; D011804:Quinolines / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D011804:Quinolines; D014665:Vasodilator Agents; D009599:Nitroprusside; C047316:flosequinan; D010100:Oxygen