Pharmacological identification of the α₂-adrenoceptor subtypes mediating the vasopressor responses to B-HT 933 in pithed rats.
It has been shown that α(2)-adrenoceptors mediate vasopressor responses in pithed rats. However, the corresponding α(2)-adrenoceptor subtypes have not been pharmacologically identified. Thus, this study set out to identify the specific subtypes (α(2A), α(2B) and α(2C)) mediating the vasopressor responses to the α(2)-adrenoceptor agonist, B-HT 933, by using the antagonists prazosin (α(1A/1B/1D)), rauwolscine (α(2A/2B/2C)), BRL44408 (α(2A)), imiloxan (α(2B)) and/or JP-1302 (α(2C)). In pithed rats, consecutive i.v. bolus injections of B-HT 933 produced dose-dependent increases in diastolic blood pressure, without affecting heart rate. The vasopressor responses to B-HT 933: (1) remained unaltered after, i.v., bolus injections of vehicles (1 ml/kg) or prazosin (10, 30, 100 and 300 μg/kg); (2) were dose-dependently blocked by rauwolscine (100 and 300 μg/kg), BRL44408 (100 and 300 μg/kg), imiloxan (1000 and 3000 μg/kg) and/or JP-1302 (10, 30, 100, and 300 μg/kg); and (3) were abolished by the combination BRL44408 (300 μg/kg)+imiloxan (1000 μg/kg)+JP-1302 (300 μg/kg). The above results support our contention that the α(2)-adrenoceptors mediating the vasopressor responses to B-HT 933 in pithed rats pharmacologically correlate with the α(2A), α(2B) and α(2C)-adrenoceptor subtypes.
Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios No. 235,Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México DF, México.
Ma Trinidad
MT
Villamil-Hernández
Oscar
O
Alcántara-Vázquez
Araceli
A
Sánchez-López
Guadalupe
G
Manrique-Maldonado
Carlos M
CM
Villalón
David
D
Centurión
D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D058669:Adrenergic alpha-2 Receptor Antagonists; D001381:Azepines; D018341:Receptors, Adrenergic, alpha-2; D014662:Vasoconstrictor Agents; C015603:azepexole