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  • Title: Characterization of the biphasic blood pressure response to alpha-methyl-5-hydroxytryptamine in anaesthetized rats.
    Author: Balasubramaniam G, Lee HS, Mah SC.
    Journal: Arch Int Pharmacodyn Ther; 1995; 329(3):360-78. PubMed ID: 8546536.
    Abstract:
    The aim of the present study was to investigate the mechanism of the biphasic blood pressure response to the 5-hydroxytryptamine2 (5-HT2) receptor agonist, alpha-methyl-5-HT (alpha-Me-5-HT) in anaesthetized rats. In conscious rats, 5-HT (2.5-15 micrograms/kg, i.v.) produced typical triphasic blood pressure responses at the higher doses. In anaesthetized rats, 5-HT produced only hypotensive responses at all doses. In conscious rats, i.v. injections of alpha-Me-5-HT (5-125 micrograms/kg) produced dose-dependent increases in mean arterial pressure with concomitant bradycardia. However, in inactin-anaesthetized rats, alpha-Me-5-HT produced biphasic blood pressure responses consisting of an initial pressor response followed by a longer lasting depressor phase. In anaesthetized rats, the 5-HT1A antagonist, spiroxatrine (1 mg/kg), and the 5-HT3 receptor antagonist, MDL72222 (0.3 mg/kg), selectively diminished the hypotensive phase without affecting the pressor phase. The 5-HT1/5-HT2 antagonist, methysergide (0.5 mg/kg), and the selective 5-HT2 antagonist, ketanserin (50 micrograms/kg), completely abolished all responses to alpha-Me-5-HT. Pretreatment with the 5-HT-selective uptake inhibitor, fluoxetine (1 mg/kg), produced a significant attenuation of the hypotensive response whilst enhancing the pressor response. Pretreatment with the 5-HT depletor, p-chlorophenylalanine (3 x 100 mg/kg/day), produced an attenuation of the hypotensive phase while the pressor response was augmented. The selective 5-HT2/5-HT2C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2- amino-propane (5-200 micrograms/kg, i.v.), produced dose-dependent pressor responses in anaesthetized rats but no hypotensive responses were observed. The results show that the 5-HT2 agonist, alpha-Me-5-HT, produces a biphasic blood pressure response in anaesthetized rats which is not seen in conscious rats. The hypotensive response is due to a nonselective activation of 5-HT1 and 5-HT3 receptors through release of 5-HT.
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