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Production by R‐α‐methylhistamine of a histamine H 3 receptor‐mediated decrease in basal vascular resistance in guinea‐pigs
Author(s) -
McLeod Robbie L.,
Gertner Sheldon B.,
Hey John A.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13846.x
Subject(s) - histamine , basal (medicine) , guinea pig , chemistry , receptor , endocrinology , medicine , pharmacology , biology , biochemistry , insulin
1 The effect of the selective histamine H 3 receptor agonist, R ‐α‐methylhistamine given intravenously (10–100 μg kg −1 ) was examined on baseline total peripheral resistance (TPR), and cardiovascular haemodynamics in bilaterally vagotomized, anaesthetized guinea‐pigs. 2 R ‐α‐methylhistamine produced a dose‐dependent hypotension and fall in TPR at 30 and 100 μg kg −1 . A decrease in heart rate (HR) was observed at a dose of 100 μg kg −1 . R ‐α‐methylhistamine (10–100 μg 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 these doses. 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 ‐α‐methylhistamine (100 μg kg −1 , i.v.). Pretreatment with the selective H 3 antagonist, thioperamide (1 mg kg −1 ), completely blocked the action of R ‐α‐methylhistamine on haemodynamic parameters. 4 To study the mechanism of action of R ‐α‐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 μg kg −1 , i.v.). Hydralazine had no effect on HR, SV or CO. 5 R ‐α‐methylhistamine (100 μg kg −1 ) did not affect the vasopressor action and increases in TPR produced by adrenaline (1 and 3 μg kg −1 ). On the other hand, the vasodilator hydralazine (1 mg kg −1 , i.v.) inhibited the effects of adrenaline (3 μg 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 ‐α‐methylhistamine are not mediated through a direct action on vascular smooth muscle. 6 In adrenalectomized guinea‐pigs, R ‐α‐methylhistamine (100 μg kg −1 ) produced a drop in BP and HR. There was no difference between the effects of R ‐α‐methylhistamine on blood pressure and heart rate in adrenalectomized and non‐adrenalectomized guinea‐pigs. 7 These results show that activation of peripheral H 3 receptors lowers basal 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.