Functional evidence for the rapid desensitization of 5-HT3 receptors on vagal afferents mediating the Bezold-Jarisch reflex

The aim of this study was to determine whether 5-hydroxytryptamine (5-HT)(3 ) receptors on cardiopulmonary afferents mediating the Bezold-Jarisch refle x (BJR) desensitize upon repeated exposure to selective agonists. BJR-media ted falls in heart rate, diastolic arterial blood pressure and cardiac outp ut elicited by the 5-HT3-receptor agonists, phenylbiguanide (100 mu g/kg, i .v.) or 2-methyl-5-HT (100 mu g/kg, i.v.), progressively diminished upon re peated injection in conscious rats. The BJR responses elicited by 5-HT (40 mu g/kg, i.v.) were markedly reduced in rats which had received the above i njections of phenylbiguanide or 2-methyl-5-HT whereas the BJR responses eli cited by L-S-nitrosocysteine (10 mu mol/kg, i.v.) were similar before and a fter the injections of the 5-HT3 receptor agonists. These findings suggest that tachyphylaxis to 5-HT3 receptor agonists may be due to the desensitiza tion of 5-HT3 receptors on cardiopulmonary afferents rather than the impair ment of the central or peripheral processing of the BJR. (C) 2000 Elsevier Science B.V. All rights reserved.