Abstract

1. 1. The effect of R-α-methylhistamine, a histamine H 3 receptor agonist, was studied on cardiovascular hemodynamics in bilateral vagotomized, anesthetized guinea pigs. 2. 2. R-α-methylhistamine (100 μg/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. 3. Pretreatment with the ganglionic blocker hexamethonium (20 mg/kg, IV) blocked the blood pressure (BP), heart rate (HR), TPR, and RPP effects of R-α-methylhistamine (100 μg/kg, IV). Hexamethonium did not block the hypotensive and TPR lowering actions of the muscarinic agonist methacholine (1 and 3 μg/kg, IV). 4. 4. Pretreatment with the α 1-adrenoceptor antagonist prazosin (0.5 mg/kg IV), blocked R-α-methylhistamine's (100 μg/kg, IV) effects on BP, TPR, and RPP. Prazosin did not antagonize the bradycardia effect of R-α-methylhistamine. 5. 5. Pretreatment with the β-adrenoceptor antagonist atenolol (1 mg/kg, IV) did not alter the BP, TPR, or RPP actions of R-α-methylhistamine. The HR effects of R-α-methylhistamine were blocked by atenolol. 6. 6. The hemodynamic effects of R-α-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 greater cardiac depressant effect as evidenced by a significant reduction in HR and cardiac output (CO). 7. 7. In summary, these results show that activation of prejunctional H 3 receptors with R-α-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-α-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 sympathetic agents to the heart.

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