Inhibitory effect of pindolol on hypoxic pulmonary vasoconstriction.
The effects of a beta-agonist (isoproterenol) and beta-antagonists (propranolol and pindolol) on hypoxic pulmonary vasoconstriction (HPV) and on changes in some chemical mediators were examined in 28 isolated blood-perfused dog lung lobes. Hypoxic challenge (4 min) was repeated twice, and each drug was administered at a bolus dose of 0.2 mg between the hypoxic periods. The first hypoxia increased pulmonary vascular resistance (PVR) by 33% or more in all groups. Both isoproterenol and pindolol inhibited the second HPV completely, but propranolol did not influence HPV. During normoxia, isoproterenol and pindolol significantly decreased PVR by 17.5 and 6.7% (P less than 0.01), respectively, but propranolol had no effect on PVR. In the control and propranolol groups, plasma levels of adenosine 3',5'-cyclic monophosphate (cAMP) significantly decreased during hypoxia, but those of prostaglandin E2, 6-ketoprostaglandin F1 alpha, and thromboxane B2 did not change. cAMP increased from 17.0 +/- 4.0 to 76.7 +/- 15.6 pmol/ml in the isoproterenol group (P less than 0.01), and prostaglandin E2 increased from 87.0 +/- 13.6 to 1,015.4 +/- 309.7 pg/ml in the pindolol group (P less than 0.05). The results suggest that the mechanism of HPV inhibition is different between isoproterenol and pindolol.
Takashio
T
T
First Department of Internal Medicine, Asahikawa Medical College, Japan.
Yamashita
H
H
Onodera
S
S
D000818:Animals; D000242:Cyclic AMP / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D010869:Pindolol / Q000494:pharmacology*; D011453:Prostaglandins / Q000097:blood; D011652:Pulmonary Circulation / Q000187:drug effects*; D013929:Thromboxane B2 / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D013929:Thromboxane B2; D010869:Pindolol; D000242:Cyclic AMP