Effects of selective alpha 1-adrenoceptor blockade in dogs with hypoxic pulmonary vasoconstriction.
The acute effects of the selective alpha 1-blocker, E-643 (Bunazosine), on experimental pulmonary hypertension (PH) caused by hypoxic pulmonary vasoconstriction (HPV) in mongrel dogs were examined. Ninety second ventilation with 5% O2 and 95% N2 was used for hypoxic stimulation. The effects of E-643 were evaluated at doses of 1, 5, 10, 20 and 50 micrograms/kg in this order until the systemic arterial mean pressure (SAm) had decreased by 20 mmHg when compared with the control value during room air ventilation. PaO2 and PaCO2 decreased by 64.6 +/- 11.0 Torr and 2.4 +/- 2.5 Torr, respectively, and the pH increased by 0.031 +/- 0.012 during hypoxic ventilation. These blood gas changes affected during hypoxic stimulation were almost the same before E-643 administration. Progression of arterial blood hypoxemia due to E-643 administration during room air ventilation was not observed. SAm decreased by 8.0 +/- 11.9 mmHg after E-643 administration, while left atrial mean pressure (LAm) and cardiac output (CO) did not change significantly. Prior to E-643 administration, mean pulmonary arterial pressure (PAm) and pulmonary vascular resistance (PVR) increased by 6.4 +/- 3.3 mmHg and 6.2 +/- 3.8 HRU, respectively, during the 90 sec hypoxic ventilation period. After E-643 administration, the increases in PAm and PVR were 3.9 +/- 1.7 mmHg and 3.3 +/- 2.3 HRU, respectively. The suppression of increases in PAm and PVR was significant. The conclusion is that E-643, a selective alpha 1-blocker, is effective at restraining HPV in the dog model.
Yoshioka
T
T
Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Osaka, Japan.
Obayashi
Y
Y
Nakanishi
N
N
Naito
M
M
Okubo
S
S
Kunieda
T
T
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011799:Quinazolines / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D011799:Quinazolines; C018176:bunazosin