The aim of the present study was to assess the role of vascular α(1D)- adrenoceptors in the sympathetic vasopressor response in vivo. Specifically, we evaluated the effect of a selective α(1D)-adrenoceptor antagonist, BMY 7378 (8-(2-(4-(2-methoxyphenyl)-I-piperazinyl)ethyl)-8-azaspiro(4,5)decane- 7,9-dione 2HCl), on the vasopressor response induced by preganglionic (T7- T9) sympathetic stimulation in the pithed rat. The vasopressor response was dose-dependently sensitive to inhibition by intravenous BMY 7378 (0.1, 0.31, 1 and 3.1 mg/kg), doses of 1 and 3.1 mg/kg being equally effective. Like BMY 7378, 5-methylurapidil (0.1, 0.31, 1 and 3.1 mg/kg) antagonized the vasopressor response to spinal stimulation; doses of 1 and 3.1 mg/kg were also equally effective. In combination experiments, BMY 7378 (1 mg/kg, iv) and the α(1A)-adrenoceptor antagonist, 5-methylurapidil (1 mg/kg, iv), showed an additive effect. The present results demonstrate that the α(1D)- adrenoceptor subtype plays an important role in the pressor response to sympathetic nerve stimulation in the pithed rat, and confirm the participation of the α(1A)-adrenoceptor subtype in the same response.
|Original language||American English|
|Number of pages||525|
|Journal||Fundamental and Clinical Pharmacology|
|State||Published - 1 Jan 1998|