Buspirone Raises Blood Pressure through Activation of Sympathetic Nervous System and by Direct Activation of alpha1-Adrenergic Receptors after Severe Hemorrhage

摘要

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 bu-spirone 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 thepressor effect of 9.9 jug/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 alpha1-adrenergic receptor antagonist prazosin (25 mug/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 alpha1-adrenergic receptors.