Pharmacological identification of the α₂-adrenoceptor subtypes mediating the vasopressor responses to B-HT 933 in pithed rats

It has been shown that α₂-adrenoceptors mediate vasopressor responses in pithed rats. However, the corresponding α₂-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 α₂-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 α₂-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.