Inhibition of sympathetic hypertensive responses in the guinea‐pig by prejunctional histamine H 3 ‐receptors

1 The effect of ( R )‐α‐methylhistamine, a selective H 3 ‐histamine receptor agonist, was examined on the neurogenic hypertension and tachycardia that is induced by stimulation of areas in the medulla oblongata of guinea‐pigs. Electrical medullary stimulation (32 Hz, 3–5 s trains, 0.5–1.0 ms square pulse, 25–400 μA) produced intensity‐dependent increases in blood pressure and a more variable tachycardia. 2 ( R )‐α‐methylhistamine inhibited the hypertension and tachycardia due to submaximal CNS stimulation. The inhibition of hypertension by ( R )‐α‐methylhistamine was dose‐dependent (10–300 μg kg −1 , i.v.) and was not seen at high intensities of stimulation. 3 ( R )‐α‐methylhistamine (300 μg kg −1 , i.v.) did not attenuate the pressor response to adrenaline (1 and 3 μg kg −1 , i.v.), indicating that the effect of ( R )‐α‐methylhistamine was not mediated by a postjunctional action on smooth muscle. 4 The inhibition of CNS‐induced hypertension by ( R )‐α‐methylhistamine (300 μg kg −1 , i.v.) was blocked by the H 3 antagonists, thioperamide (ID 50 = 0.39 mg kg −1 , i.v.), impromidine (ID 50 = 0.22 mg kg −1 , i.v.) and burimamide (ID 50 = 6 mg kg −1 , i.v.). The rank order potency of these antagonists is consistent with activity at the H 3B receptor subtype. Chlorpheniramine (30 μg kg −1 , i.v.) and cimetidine (3 mg kg −1 , i.v.) did not antagonize the inhibition of CNS‐hypertension by ( R )‐α‐methylhistamine. 5 These results suggest that ( R )‐α‐methylhistamine inhibits sympathetic hypertensive responses in guinea‐pigs by activation of prejunctional H 3 ‐receptors, possibly located on postganglionic nerve terminals. Furthermore, on the basis of the rank order potency to different H 3 ‐antagonists, it appears that the H 3B ‐receptor subtype is involved with H 3 ‐receptor responses on vascular sympathetic nerves.