Endothelium‐dependent relaxation of rabbit middle cerebral artery to a histamine H₃‐agonist is reduced by inhibitors of nitric oxide and prostacyclin synthesis

Abstract

1 The possible involvement of prostanoids and endothelium-derived relaxing factor (EDRF) in the vasodilatation induced by a histamine H3-agonist was examined in the rabbit perfused middle cerebral artery preconstricted with K + (50mM). 2 The endothelium-dependent relaxation to (R)-x-methylhistamine [(R)-a-MeHA] was competitively antagonized by thioperamide (an H3-antagonist) with a pA2 of 9.05, but unaffected by propranolol, atropine, L-and D-sulpiride. This effect was stereoselective since the (S)-isomer was 100 times less potent than the (R)-isomer. 3 Two inhibitors of nitric oxide synthesis, N0-nitro-L-arginine methyl ester (L-NAME) and NGmonomethyl-L-arginine (L-NMMA), inhibited the relaxation induced by (R)-a-methylhistamine. The inhibitory effects of 10 5 M NG-nitro-L-arginine methyl ester and 10-5 M N0-monomethyl-L-arginine were reversed by equimolar concentrations of L-arginine, but strongly enhanced by 1O-4M tranylcypromine. Tranylcypromine alone (10-5M-10-4M) partially reduced the (R)-a-methylhistamine-induced relaxation. Both dexamethasone and indomethacin also inhibited this relaxation. 4 The results suggest that the H3-mediated relaxation of the rabbit middle cerebral artery may involve release of both a prostanoid, probably prostacyclin, and endothelium-derived relaxing factor. The relaxant effects of these two endogenous compounds appear to be synergistic.

R-(-)-.ALPHA.-Methylhistamine, a Histamine H3 Receptor Agonist, Induces Endothelium-Dependent Vasodilation in Rat Mesenteric Resistance Arteries

“…To remove the vascular endothelium, preparations with resting tone were perfused with a 1.80 mg/ml solution of sodium deoxycholate (Sigma Aldrich Japan Co., Tokyo, Japan) in saline for 30 s. This caused a transient increase (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) in perfusion pressure. Then, the preparations were rinsed with sodium deoxycholate-free Krebs solution for 40 min.…”

“…Evidence has accumulated that NO, PGI 2 and/or EDHFs play a prominent role in the tone control of the endothelium contact arteries. [19][20][21][22][23] Therefore, the purpose of the present study was to investigate the vascular responses mediated by histamine H 3 receptors using a-methylhistamine and the underlying mechanisms in the mesenteric vascular bed of the rat. …”

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

“…(C) Glutamatergic corticostriatal synaptic transmission (co-str) is reduced by R-a-methylhistamine, an example of an H 3 -heteroreceptor action. 626 release (Ea Kim et al, 1992). Finally, there is a report that H 3 receptor activation can stimulate adrenocorticotropic hormone release from the pituitary cell line AtT-20 (Clark et al, 1992).…”

Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn

“…PGI 2 , NO, and possibly an EDHF contribute to methacholine and bradykinin-induced endothelium-dependent vascular relaxation of ovine coronary artery precontracted with U46619 (Pratt et al, 1996). In addition, removal of the endothelium or pretreatment with inhibitors of both NO and PGI 2 synthesis reduces (R)-␣-methyl-histamineinduced relaxation of rabbit middle cerebral artery rings precontracted with KCl (Ea Kim et al, 1992) and increases the vasoconstriction response of goat middle cerebral artery to 5-hydroxytryptamine (Miranda et al, 1993). In the pulmonary vasculature, the contribution of PGI 2 to endothelium-dependent relaxation seems to be different in pulmonary arteries and veins and between species.…”