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EVIDENCE SUGGESTING THAT THE 5-HT2 ANTAGONIST ICI 169,369 ACTIVATES VAGAL AFFERENTS AND IN ADDITION HAS A CENTRAL HYPOTENSIVE ACTION IN ANESTHETIZED RATS

PIRES, JGP; RAMAGE, AG; (1990) EVIDENCE SUGGESTING THAT THE 5-HT2 ANTAGONIST ICI 169,369 ACTIVATES VAGAL AFFERENTS AND IN ADDITION HAS A CENTRAL HYPOTENSIVE ACTION IN ANESTHETIZED RATS. J AUTON PHARMACOL , 10 (6) 345 - 351.

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Abstract

1 The cardiovascular effects of the 5-HT2 antagonist ICI 169,369 have been investigated in pentobarbitone anaesthetized rats and in pithed rats whose blood pressure was supported by a vasopressin infusion.2 In anaesthetized rats, cumulative doses (0.1-3.0 mg kg-1) of ICI 169,369 caused dose-related large transient falls in heart rate and blood pressure followed by a slow dose-related decline in both parameters.3 Pretreatment with atropine methonitrate (1 mg kg-1) alone or in combination with atenolol (1 mg kg-1) or bi-vagotomy blocked the transient changes in blood pressure and heart rate caused by ICI 169,369. The long-term fall in heart rate was also attenuated by either atropine or atenolol; however, the combination of atenolol and atropine was more effective. None of the above pretreatments affected the long-term fall in blood pressure caused by ICI 169,369.4 The cardiovascular effects of ICI 169,369 were unaffected by pretreatment with MDL 72222 (1 mg kg-1) and failed to show cross-tachyphylaxis with phenylbiguanide.5 In pithed rats whose blood pressure was maintained with vasopressin, ICI 169,369 failed to cause any of the above transient and long-term effects on blood pressure and heart rate.6 The study indicates that ICI 169,369 is capable of stimulating cardiopulmonary afferents through a non 5-HT3 receptor mechanism and has a central hypotensive action.

Type: Article
Title: EVIDENCE SUGGESTING THAT THE 5-HT2 ANTAGONIST ICI 169,369 ACTIVATES VAGAL AFFERENTS AND IN ADDITION HAS A CENTRAL HYPOTENSIVE ACTION IN ANESTHETIZED RATS
Keywords: BLOOD-PRESSURE, RECEPTOR ANTAGONISTS, NERVE, 5-HYDROXYTRYPTAMINE, KETANSERIN, POTENT
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: http://discovery.ucl.ac.uk/id/eprint/167136
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