The 5‐HT 1 ‐like receptors mediating inhibition of sympathetic vasopressor outflow in the pithed rat: operational correlation with the 5‐HT 1A , 5‐HT 1B and 5‐HT 1D subtypes

It has been suggested that the inhibition of sympathetically‐induced vasopressor responses produced by 5‐hydroxytryptamine (5‐HT) in pithed rats is mediated by 5‐HT 1 ‐like receptors. The present study has re‐analysed this suggestion with regard to the classification schemes recently proposed by the NC‐IUPHAR subcommittee on 5‐HT receptors. Intravenous (i.v.) continuous infusions of 5‐HT and the 5‐HT 1 receptor agonists, 8‐OH‐DPAT (5‐HT 1A ), indorenate (5‐HT 1A ), CP 93,129 (5‐HT 1B ) and sumatriptan (5‐HT 1B/1D ), resulted in a dose‐dependent inhibition of sympathetically‐induced vasopressor responses. The sympatho‐inhibitory responses induced by 5‐HT, 8‐OH‐DPAT, indorenate, CP 93,129 or sumatriptan were analysed before and after i.v. treatment with blocking doses of the putative 5‐HT receptor antagonists, WAY 100635 (5‐HT 1A ), cyanopindolol (5‐HT 1A/1B ) or GR 127935 (5‐HT 1B/1D ). Thus, after WAY 100635, the responses to 5‐HT and indorenate, but not to 8‐OH‐DPAT, CP 93,129 and sumatriptan, were blocked. After cyanopindolol, the responses to 5‐HT, indorenate and CP 93,129 were abolished, whilst those to 8‐OH‐DPAT and sumatriptan (except at the lowest frequency of stimulation) remained unaltered. In contrast, after GR 127935, the responses to 5‐HT, CP 93,129 and sumatriptan, but not to 8‐OH‐DPAT and indorenate, were abolished. In additional experiments, the inhibition induced by 5‐HT was not modified after 5‐HT 7 receptor blocking doses of mesulergine. The above results suggest that the 5‐HT 1 ‐like receptors, which inhibit the sympathetic vasopressor outflow in pithed rats, display the pharmacological profile of the 5‐HT 1A , 5‐HT 1B and 5‐HT 1D , but not that of 5‐HT 7 , receptors.