In vitro relaxation of dog cerebral veins in response to histamine is mediated by histamine H2 receptors.

There is little information on the histamine receptor mechanisms involved in cerebral venodilation, thus the role of histamine present in human cerebrospinal fluid is difficult to assess. In isolated canine pial veins, concentration-response curves to histamine (10[-7]-10[-3] M), the histamine H1 receptor agonist, 2-pyridylethylamine (10[-6]-10[-2] M), the histamine H2 receptor agonist, dimaprit (S-(3-dimethylaminopropyl) isothiourea dihydrochloride, 10[-6]-10[-2] M), and the histamine H3 receptor agonist, imetit (S-[2-(1 midazol-4-yl)ethyl]isothiourea dihydrobromide, 10[-7]-10[-3] M) were isometrically determined. In resting veins, histamine, 2-pyridylethylamine and dimaprit had no significant effect, whereas in endothelin-1-precontracted veins, these drugs produced concentration-dependent relaxation (Emax in % of active tone and pD2 were: for histamine, 72 +/- 6 and 5.36 +/- 0.09; for 2-pyridylethylamine, 59 +/- 5 and 3.28 +/- 0.05; for dimaprit, 65 +/- 7 and 4.81 +/- 0.10, respectively). The relaxations in response to histamine and dimaprit were competitively antagonized by the histamine H2 receptor antagonist, cimetidine (3 x 10[-6]-10[-4] M) (pA2 = 6.07 +/- 0.03 for histamine, and 6.09 +/- 0.07 for dimaprit), but were not affected by the histamine H1 receptor antagonist, chlorpheniramine (10[-6] M) or the histamine H3 receptor antagonist, thioperamide (N-cyclohexyl-4-(1-H-imidazol-4-yl)-1-piperidine-carbothioamide maleate, 10[-6] M). The relaxation in response to 2-pyridylethylamine was inhibited by cimetidine (10[-5] M), but not by chlorpheniramine (10[-6] M). Imetit produced a small contraction in resting veins (14 +/- 4 mg) and precontracted veins (20 +/- 3 mg), which was not modified by thioperamide (10[-6] M). The relaxation of veins in response to histamine was not modified by endothelium removal, nor by the inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester (10[-4] M), or the cyclooxygenase inhibitor, meclofenamate (10[-5] M). Therefore, in pial veins: (1) histamine produces relaxation by activation of histamine H2 receptors, probably located in the smooth musculature, with no participation of histamine H1 and H3 receptors, and (2) endothelium, nitric oxide and prostanoids are probably not involved in the relaxation in response to histamine.