Inhibition of sympathetic hypertensive responses in the guinea-pig by prejunctional histamine H3-receptors.
Br J Pharmacol
; 107(2): 347-51, 1992 Oct.
Article
em En
| MEDLINE
| ID: mdl-1330174
ABSTRACT
1. The effect of (R)-alpha-methylhistamine, a selective H3-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 microA) produced intensity-dependent increases in blood pressure and a more variable tachycardia. 2. (R)-alpha-methylhistamine inhibited the hypertension and tachycardia due to submaximal CNS stimulation. The inhibition of hypertension by (R)-alpha-methylhistamine was dose-dependent (10-300 micrograms kg-1, i.v.) and was not seen at high intensities of stimulation. 3. (R)-alpha-methylhistamine (300 micrograms kg-1, i.v.) did not attenuate the pressor response to adrenaline (1 and 3 micrograms kg-1, i.v.), indicating that the effect of (R)-alpha-methylhistamine was not mediated by a postjunctional action on smooth muscle. 4. The inhibition of CNS-induced hypertension by (R)-alpha-methylhistamine (300 micrograms kg-1, i.v.) was blocked by the H3 antagonists, thioperamide (ID50 = 0.39 mg kg-1, i.v.), impromidine (ID50 = 0.22 mg kg-1, i.v.) and burimamide (ID50 = 6 mg kg-1, i.v.). The rank order potency of these antagonists is consistent with activity at the H3B receptor subtype. Chlorpheniramine (30 micrograms kg-1, i.v.) and cimetidine (3 mg kg-1, i.v.) did not antagonize the inhibition of CNS-hypertension by (R)-alpha-methylhistamine. 5. These results suggest that (R)-alpha-methylhistamine inhibits sympathetic hypertensive responses in guinea-pigs by activation of prejunctional H3-receptors, possibly located on postganglionic nerve terminals. Furthermore, on the basis of the rank order potency to different H3-antagonists, it appears that the H3B-receptor subtype is involved with H3-receptor responses on vascular sympathetic nerves.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sistema Nervoso Simpático
/
Pressão Sanguínea
/
Bulbo
/
Receptores Histamínicos
/
Metilistaminas
/
Agonistas dos Receptores Histamínicos
Limite:
Animals
Idioma:
En
Ano de publicação:
1992
Tipo de documento:
Article