8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) is a new
serotonin (5-HT) receptor agonist that binds selectively to the 5-HT1A binding site. In the present paper we investigated the cardiovascular effects of
8-OH-DPAT in the normotensive Sprague-Dawley rat and in the spontaneously hypertensive rat. The acute i.v. administration of
8-OH-DPAT (5-150 micrograms/kg) was in both rat strains associated with a biphasic blood pressure response and a
bradycardia. The initial pressor response was due to a direct vascular effect of
8-OH-DPAT involving activation of alpha-
adrenoceptors since it was present in pithed rats and in
reserpine pretreated rats and since it was attenuated by
prazosin. The longer lasting
hypotension was not due to a direct vascular relaxation or a presynaptic inhibition of transmitter release since the
hypotension was not evident in pithed rats and since
8-OH-DPAT did not influence the pressor responses to electrical stimulation in pithed rats. Rather, the combination of
hypotension and
bradycardia would suggest a central site of action although the intracerebroventricular (lat. ventricles) route of administration was not more efficient (to induce
hypotension) than i.v. administration. At least the
bradycardia was mediated by changes in vagal as well as sympathetic discharge since it was prevented by pretreatment with
atropine and
propranolol in combination but not by pretreatment with either agent alone. The cardiovascular effects of
8-OH-DPAT were not prevented by pretreatment with
methergoline,
methiothepin,
pirenperone or cianserine or by
5-HT depletion by means of
p-chlorophenylalanine, which suggests that the putative
5-HT receptor that is responsible for the
hypotension and
bradycardia to
8-OH-DPAT is not of a presynaptic type and does not have the pharmacological characteristics of a general
5-HT1 receptor.