α1D‐Adrenoceptors contribute to the neurogenic vasopressor response in pithed rats

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Abstract
Summary—The aim of the present study was to assess the role of vascular α1D‐adrenoceptors in the sympathetic vasopressor response in vivo. Specifically, we evaluated the effect of a selective α1D‐adrenoceptor antagonist, BMY 7378 (8‐(2‐(4‐(2‐methoxyphenyl)‐1‐piperazinyl)ethyl)‐8‐azaspiro(4,5)decane‐7,9‐dione 2HCI), 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 α1A‐adrenoceptor antagonist, 5‐methylurapidil (1 mg/kg, iv), showed an additive effect. The present results demonstrate that the α1D‐adrenoceptor subtype plays an important role in the pressor response to sympathetic nerve stimulation in the pithed rat, and confirm the participation of the α1A‐adrenoceptor subtype in the same response.