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Potentiation of responses to sympathetic nerve stimulation and vasoconstrictor agents by SK&F 103829 in the feline mesenteric circulation
Author(s) -
Taylor E. Michael,
Kaumann Alberto J.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14054.x
Subject(s) - ketanserin , methoxamine , endocrinology , medicine , stimulation , angiotensin ii , prazosin , agonist , mesenteric arteries , artery , chemistry , receptor , serotonin , antagonist , 5 ht receptor
1 The amplification of vasoconstrictor effects of several agonists and sympathetic nerve stimulation, caused by 5‐HT 2 receptor activation, was studied in the autoperfused mesenteric circulation of anaesthetized cats. To produce long lasting and selective 5‐HT 2 receptor stimulation we used SK&F 103829 (2,3,4,5 tetrahydro‐8[methyl‐sulphonyl]‐1H3‐benzazepin‐7‐ol methensulphonate). We assessed that SK&F 103829 was a strong contractile partial agonist in isolated preparations of rat tail artery and calf pulmonary artery. 2 The intrinsic activity of SK&F 103829 with respect to 5‐hydroxytryptamine (5‐HT) was 0.8 in rat tail artery and 0.6 in calf pulmonary artery. SK&F 103829‐induced contractile responses were surmountably antagonized by ketanserin with a potency expected from its affinity for 5‐HT 2 receptors. SK&F 103829 surmountably antagonized the effects of 5‐HT in rat tail artery with a p K p of 5.8. 3 Concentrations of SK&F 103829 causing greater than threshold constrictions enhanced vasoconstrictor responses of sympathetic nerve stimulation, noradrenaline, angiotensin II, methoxamine and α, β‐methylene ATP in the mesenteric arterial bed. Increases in mesenteric arterial pressure by noradrenaline, observed in the presence of prazosin, were also potentiated by SK&F 103829. 4 Ketanserin prevented both the constrictor effect of SK&F 103829 and the SK&F 103829‐evoked potentiation of the responses to noradrenaline and angiotensin II in the mesenteric arterial bed. Ketanserin, however, failed to abolish (once established) the SK&F 103829‐evoked potentiation of the constrictor effects caused by both noradrenaline and angiotensin II. 5 Short lasting constrictor effects of 5‐HT were reversed to dilator effects by SK&F 103829 in both the mesenteric arterial and venous bed, thereby revealing the existence of vasodilator 5‐HT receptors. 6 The main finding is consistent with a sensitization of the mesenteric arterial bed to vasoconstrictor responses mediated through α 1 ‐ and α 2 ‐adrenoceptors, angiotensin II receptors and purinoceptors by SK&F 103829‐evoked activation of 5‐HT 2 receptors. This property, together with the direct constrictor effect of the mesenteric arterial bed suggest that SK&F 103829 can reduce portal venous flow thereby being a useful therapeutic principle for the treatment of portal hypertension.