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CARDIOVASCULAR

Buspirone Raises Blood Pressure through Activation of Sympathetic Nervous System and by Direct Activation of 1-Adrenergic Receptors after Severe Hemorrhage

Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois

5-Hydroxytryptamine 1A (5-HT1A) receptor agonists reverse the hypotensive and sympathoinhibitory responses to severe hemorrhage in rats. To determine whether 5-HT1A receptor-mediated pressor responses in hypovolemic animals are due to sympathoexcitation and/or direct vasoconstriction, blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) responses to the partial 5-HT1A receptor agonist buspirone or the more selective, full 5-HT1A receptor agonist (+)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were compared in intact and ganglionic blocked, hemorrhaged Sprague-Dawley rats. Buspirone produced dose-dependent increases in BP (110 ± 4^**, 86 ± 4^**, 65 ± 7 mm Hg), HR [369 ± 10^**, 337 ± 14, 277 ± 16 beats per minute (bpm)], and RSNA (114 ± 36^**, 34 ± 21, -23 ± 25% baseline for 0.2, 0.1, and 0 mg/kg; ^**p < 0.01 versus 0 mg/kg, 3 min after injection). Ganglionic blockade with hexamethonium chloride blocked the pressor effect of 9.9 µg/kg 8-OH-DPAT and attenuated, but did not block, the pressor response to 0.2 mg/kg buspirone (85 ± 7 versus 46 ± 6 mm Hg for buspirone + ganglionic blockade versus saline + ganglionic blockade; p < 0.01). In subsequent tests, rats treated with the selective 1-adrenergic receptor antagonist prazosin (25 µg/kg) continued to show extensive tachycardic (+73 ± 26 bpm) and sympathoexcitatory (128 ± 55% baseline) responses to 0.2 mg/kg buspirone. Ganglionic blockade combined with prazosin completely blocked all responses to buspirone. Buspirone (0.2 mg/kg) produced significant bradycardic (-89 ± 12 bpm; p < 0.01) and sympathoinhibitory (-72 ± 7% baseline; p < 0.01) responses in euvolemic rats 3 min after injection. It is concluded that the pressor effect of buspirone is unique to hypovolemic animals and is mediated by sympathetic activation as well as direct activation of vascular 1-adrenergic receptors.

Address correspondence to: Dr. Karie Scrogin, Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153. E-mail: kscrogi{at}lumc.edu

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