Studies on epinephrine-induced lung edema in the rat. I. Selective alpha 1-adrenoceptor involvement.
Phentolamine (Phe) prevents the induction by epinephrine (E: 1800 nmol/kg, i.v.) of lung edema (LE) in urethane-anesthetized and bivagotomized rats in a dose-related manner (from 246 to 3933 nmol/kg, i.v.). Since Phe blocks and E activates both alpha 1- and alpha 2-adrenoceptors, the evidence does not allow us to link LE to selective (alpha 1 or alpha 2) or non-selective (alpha 1 + alpha 2) alpha-adrenoceptor activation. Accordingly, we tried to find out whether: phenylephrine (PE), a selective alpha 1-adrenoceptor agonist, and B-HT 920, a selective alpha 2-adrenoceptor agonist, would cause LE; prazosin (Praz), a selective alpha 1-adrenoceptor antagonist, and yohimbine (Yoh), a selective alpha 2-adrenoceptor antagonist, would protect rats against LE caused by E or PE. We found that: 1) PE (from 736 to 5892 nmol/kg, i.v.), but not B-HT 920 (from 190 to 12200 nmol/kg, i.v.), caused LE, while both drugs increased arterial blood pressure; 2) Praz prevented induction of LE, whether by E (1800 nmol/kg, i.v.) or by PE (5892 nmol/kg, i.v.), in a dose-related manner (from 15 to 119 nmol/kg, i.v.). In contrast, Yoh was ineffective at doses up to 7675 nmol/kg, i.v. We conclude, therefore, that E-induced LE in urethane-anesthetized and bivagotomized rats strictly depends on alpha 1-adrenoceptor activation. The outcome of E-induced LE is usually rat death, the incidence of which depends on the dose. Since alpha 1-adrenoceptor agonists rank in the same order of potency for the induction of death as for that of LE, and since Phe and Praz protect from death at LE-preventing doses, there seems to be some link between LE and death, even though protection against death is obtained with doses of antagonists lower than those abolishing induction of LE. Finally, alpha 1-agonists cause maximum arterial hypertension at all doses used, irrespective of induction of LE and of protective pretreatment against LE.
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D003983:Dibenzylchlorethamine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D008680:Metaraminol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011217:Practolol / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015016:Yohimbine; D003983:Dibenzylchlorethamine; C024763:talipexole; D008680:Metaraminol; D011433:Propranolol; D003000:Clonidine; D011217:Practolol; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine