Effects of dopexamine hydrochloride on hypoxic pulmonary vasoconstriction in isolated rat lung.
Dopexamine hydrochloride is a new analog of dopamine that lowers systemic vascular resistance and has positive inotropic and chronotropic properties, but lacks the alpha-adrenoceptor agonist activity of dopamine. The effects of dopexamine on hypoxic pulmonary vasoconstriction (HPV) are not known. We investigated this using an isolated, blood-perfused, and ventilated rat lung model. To study HPV, the ventilating gas was changed from an FIO2 of 0.21 to 0.03 and dopexamine hydrochloride was added. At blood concentrations of 100, 200, and 300 ng/ml, dopexamine caused a significant decrease in HPV of 22 +/- 3%, 31 +/- 4%, and 58 +/- 4% (mean +/- SEM, p less than .05), respectively. This effect was blocked completely by pretreatment of the preparation with propranolol (0.5 mg/kg, p less than .05). Dopexamine also induced significant (p less than .05) vasodilation of the pulmonary circulation preconstricted under normoxic conditions with prostaglandin F2 alpha, suggesting that the effects of the drug were not specific to hypoxia. We conclude that dopexamine inhibits HPV and vasodilates the pulmonary circulation by stimulation of beta 2 adrenoceptors.
McCormack
D G
DG
Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Barnes
P J
PJ
Evans
T W
TW
D000818:Animals; D015237:Dinoprost / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology; D008168:Lung / Q000098:blood supply; D008171:Lung Diseases / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012121:Respiration, Artificial; D014661:Vasoconstriction; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D014665:Vasodilator Agents; C046318:dopexamine; D011433:Propranolol; D015237:Dinoprost; D004298:Dopamine