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Titolo:
PRODUCTION BY R-ALPHA-METHYLHISTAMINE OF A HISTAMINE H-3 RECEPTOR-MEDIATED DECREASE IN BASAL VASCULAR-RESISTANCE IN GUINEA-PIGS
Autore:
MCLEOD RL; GERTNER SB; HEY JA;
Indirizzi:
SCHERING PLOUGH CORP,RES INST,DEPT ALLERGY,2015 GALLOPING HILL RD KENILWORTH NJ 07033 SCHERING PLOUGH CORP,RES INST,DEPT ALLERGY,2015 GALLOPING HILL RD KENILWORTH NJ 07033 UMDNJ,NEW JERSEY MED SCH,DEPT PHARMACOL & TOXICOL NEWARK NJ 00000
Titolo Testata:
British Journal of Pharmacology
fascicolo: 2, volume: 110, anno: 1993,
pagine: 553 - 558
SICI:
0007-1188(1993)110:2<553:PBROAH>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT-BRAIN; PRESYNAPTIC INHIBITION; ENDOGENOUS HISTAMINE; RELEASE; LIGANDS; (R)-ALPHA-METHYLHISTAMINE; H-3-RECEPTORS; H3-RECEPTORS; ACTIVATION; RELAXATION;
Keywords:
HISTAMINE H-3 RECEPTORS; R-ALPHA-METHYLHISTAMINE; HEMODYNAMICS; CARDIAC OUTPUT; TOTAL PERIPHERAL RESISTANCE; PRESYNAPTIC INHIBITION; SYMPATHETIC NEUROTRANSMISSION; ADRENALECTOMY; THIOPERAMIDE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
28
Recensione:
Indirizzi per estratti:
Citazione:
R.L. Mcleod et al., "PRODUCTION BY R-ALPHA-METHYLHISTAMINE OF A HISTAMINE H-3 RECEPTOR-MEDIATED DECREASE IN BASAL VASCULAR-RESISTANCE IN GUINEA-PIGS", British Journal of Pharmacology, 110(2), 1993, pp. 553-558

Abstract

1 The effect of the selective histamine H-3 receptor agonist, R-alpha-methylhistamine given intravenously (10-100 mug kg-1) was examined onbaseline total peripheral resistance (TPR), and cardiovascular haemodynamics in bilaterally vagotomized, anaesthetized guinea-pigs. 2 R-alpha-methylhistamine produced a dose-dependent hypotension and fall in TPR at 30 and 100 mug kg-1. A decrease in heart rate (HR) was observed at a dose of 100 mug kg-1. R-alpha-methylhistamine (10-100 mug kg-1) also produced a dose-dependent fall in rate pressure product (RPP). There was no effect on cardiac output (CO) or stroke volume (SV) at thesedoses. 3 Histamine H-1 and H-2 blockade in animals pretreated with a combination of chlorpheniramine (0.3 mg kg-1) and cimetidine (3.0 mg kg-1) did not alter the haemodynamic actions of R-alpha-methylhistamine(100 mug kg-1, i.v.). Pretreatment with the selective H-3 antagonist,thioperamide (1 mg kg-1), completely blocked the action of R-alpha-methylhistamine on haemodynamic parameters. 4 To study the mechanism of action of R-alpha-methylhistamine, the vasodilator hydralazine (1 mg kg-1, i.v.) was used. Hydralazine lowered BP, TRP and RPP in guinea-pigs pretreated with ipratropium (50 mug kg-1, i.v.). Hydralazine had no effect on HR, SV or CO. 5 R-alpha-methylhistamine (100 mug kg-1) did not affect the vasopressor action and increases in TPR produced by adrenaline (1 and 3 mug kg-1). On the other hand, the vasodilator hydralazine (1 mg kg-1, i.v.) inhibited the effects of adrenaline (3 mug kg-1)on TPR and RPP. The effect of both doses of adrenaline on BP were attenuated by hydralazine. Therefore, the inhibitory effects of R-alpha-methylhistamine are not mediated through a direct action on vascular smooth muscle. 6 In adrenalectomized guinea-pigs, R-alpha-methylhistamine (100 mug kg-1) produced a drop in BP and HR. There was no differencebetween the effects of R-alpha-methylhistamine on blood pressure and heart rate in adrenalectomized and non-adrenalectomized guinea-pigs. 7These results show that activation of peripheral H-3 receptors lowersbasal BP, HR and TPR, most likely by a peripheral prejunctional mechanism. The fall in BP and TPR is probably due to a decrease in noradrenaline release from sympathetic effector nerves innervating the resistance blood vessels.

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Documento generato il 15/01/21 alle ore 19:52:26