The cardiovascular effects of centrally administered 5-hydroxytryptamine in the conscious normotensive and hypertensive rat.

The cardiovascular effects of centrally administered 5-hydroxytryptamine (5-HT) have been analysed in conscious normotensive and hypertensive rats. In conscious normotensive rats, 5-HT, (1-30 micrograms) administered intracerebroventricularly (i.c.v.) produced profound and immediate dose-related decreases in heart rate and small increases in blood pressure. The initial pressor responses were followed by secondary secondary depressor responses at high doses of 5-HT. Similar effects were produced by 5-HT i.c.v. in conscious DOCA-salt and spontaneously hypertensive rats, although the magnitude of the pressor responses was substantially greater in hypertensive than normotensive rats. Pretreatment with either N-methylatropine or atenolol intra-arterially reduced the 5-HT-induced bradycardia in normotensive rats; the reduction was enhanced when both antagonists were given in combination. The 5-HT2 antagonist, cyproheptadine (10 micrograms i.c.v.) increased basal blood pressure and heart rate in normotensive rats. Subsequent administration of 5-HT i.c.v. produced biphasic effects on heart rate consisting of an initial tachycardia followed by a marked bradycardia. Methysergide (10 micrograms i.c.v.) pretreatment did not alter resting heart rate, but attenuated the 5-HT induced bradycardia. A higher dose of methysergide, (30 micrograms i.c.v.), decreased resting blood pressure and heart rate. This study has demonstrated, therefore, that the 5-HT induced bradycardia is produced by not only a centrally mediated decrease in sympathetic tone, but also an increase in vagal drive to the heart. The bradycardia is antagonised by centrally administered methysergide, but not by cyproheptadine, which suggests that it is probably mediated through a '5-HT1-like' receptor mechanism.