Effects of antagonists of 5-hydroxytryptamine on blood pressure in the anesthetised spontaneously hypertensive rat.

In pithed spontaneously hypertensive rats (SHR), the selective 5-HT2-receptor antagonist LY 53857 (1 mg/kg) had no effect on alpha 1- or alpha 2-adrenoceptors, but ketanserin (1 mg/kg) had some potency as an alpha 1-adrenoceptor antagonist, being approximately 100 times less potent than prazosin. Both ketanserin and LY 53857 (0.01 mg/kg) markedly antagonized the pressor response to 5-HT. In anesthetised SHR, both ketanserin and LY 53857 (1 mg/kg) significantly lowered diastolic blood pressure (DBP) alone or subsequent to administration of prazosin (1 mg/kg). In conscious SHR, LY 53857 (1 mg/kg) and ketanserin (0.1 mg/kg) did not significantly affect DBP, but ketanserin (1 mg/kg) significantly lowered DBP. It is concluded that ketanserin lowers DBP in conscious SHR mainly by alpha 1-adrenoceptor blockade, but that in anaesthetised SHR additional actions, possibly 5-HT2 blockade, contribute to the blood pressure lowering effects.