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Titolo:
HEMODYNAMIC PROFILE OF ACTIVATION OF HISTAMINE H-3 RECEPTORS BY R-ALPHA-METHYLHISTAMINE IN THE GUINEA-PIG
Autore:
MCLEOD RL; GERTNER SB; HEY JA;
Indirizzi:
SCHERING PLOUGH CORP,RES INST,ALLERGY,2015 GALLOPING HILL RD KENILWORTH NJ 07033 UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT PHARMACOL & TOXICOL NEWARK NJ 07103
Titolo Testata:
General pharmacology
fascicolo: 6, volume: 27, anno: 1996,
pagine: 1001 - 1007
SICI:
0306-3623(1996)27:6<1001:HPOAOH>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT-BRAIN CORTEX; NORADRENALINE RELEASE; MEDIATED INHIBITION; H3 RECEPTORS; RESPONSES; IDENTIFICATION; H2-RECEPTORS; H3-RECEPTORS; RELAXATION; PULMONARY;
Keywords:
HISTAMINE H-3 RECEPTORS; R-ALPHA-METHYLHISTAMINE; HEMODYNAMICS; PRESYNAPTIC INHIBITION; SYMPATHETIC NEUROTRANSMISSION; PRAZOSIN; ATENOLOL; HEXAMETHONIUM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
R.L. Mcleod et al., "HEMODYNAMIC PROFILE OF ACTIVATION OF HISTAMINE H-3 RECEPTORS BY R-ALPHA-METHYLHISTAMINE IN THE GUINEA-PIG", General pharmacology, 27(6), 1996, pp. 1001-1007

Abstract

1. The effect of R-alpha-methylhistamine, a histamine H-3 receptor agonist, was studied on cardiovascular hemodynamics in bilateral vagotomized, anesthetized guinea pigs. 2. R-alpha-methylhistamine (100 mu g/kg, IV) a dose that selectively activates histamine H-3 receptors, produced hypotension and bradycardia. Total peripheral resistance (TPR) and rate pressure product (RPP) were also decreased at this dose. 3. Pretreatment with the ganglionic blocker hexamethonium (20 mg/kg, IV) blocked the blood pressure (BP), heart rate (HR), TPR, and RPP effects ofR-alpha-methylhistamine (100 mu g/kg, IV). Hexamethonium did not block the hypotensive and TPR lowering actions of the muscarinic agonist methacholine (1 and 3 mu g/kg, IV). 4. Pretreatment with the alpha(1)-adrenoceptor antagonist prazosin (0.5 mg/kg IV), blocked R-alpha-methylhistamine's (100 mu g/kg, IV) effects on BP, TPR, and RPP. Prazosin did not antagonize the bradycardia effect of R-alpha-methylhistamine. 5. Pretreatment with the beta-adrenoceptor antagonist atenolol (1 mg/kg, IV) did not alter the BP, TPR, or RPP actions of R-alpha-methylhistamine. The HR effects of R-alpha-methylhistamine were blocked by atenolol. 6. The hemodynamic effects of R-alpha-methylhistamine were compared to the hemodynamic profile of the calcium channel blocker, verapamil(0.5 mg/kg, IV). Verapamil had little effect on TRP and had a greatercardiac depressant effect as evidenced by a significant reduction in HR and cardiac output (CO). 7. In summary, these results show that activation of prejunctional H-3 receptors with R-alpha-methylhistamine decreases basal, BP, HR, TPR, and RPP in anesthetized guinea pigs. The fall in BP is mediated by a decrease in TPR. Furthermore, the inhibitory effects of R-alpha-methylhistamine on sympathetic control of the vasculature appears to impart a greater physiologic effect on the H-3-histamine mediated hypotension than its inhibitory effects on sympatheticagents to the heart.

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Documento generato il 16/01/21 alle ore 23:11:30