Abstract

The mode of action of i.v. injected ketanserin, LY 53857 and other 5-hydroxytryptamine (5-HT2) receptor antagonists in lowering blood pressure was examined in anesthetized and pithed spontaneously hypertensive rats (SHR). In pithed SHR, LY 53857 (1 mg kg-1) had no effect on alpha-1 or alpha-2 adrenoceptors, but ketanserin (1 mg kg-1) 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-1) markedly antagonized the pressor response to 5-HT. In pentobarbitone-anesthetized SHR, ketanserin and LY 53857 (1 mg kg-1) were equieffective at lowering diastolic blood pressure (DBP) subsequent to prazosin (1 mg kg-1), although ketanserin (1 mg kg-1) was more effective at lowering DBP in the absence of prazosin. The blood pressure lowering effects of LY 53857 were unaffected by the peripherally acting 5-HT2 receptor antagonist BW 501C. Neither LY 53857 nor ketanserin lowered DBP in pithed rats. It is concluded that ketanserin in high doses lowers DBP in anesthetized SHR partly by alpha-1 adrenoceptor blockade, but that ketanserin and LY 53857 in high doses have additional blood pressure lowering properties, unrelated to peripheral 5-HT2 receptor blockade.