Analysis of an H₁ receptor‐mediated, zinc‐potentiated vasoconstrictor action of the histidyl dipeptide carnosine in rabbit saphenous vein

Abstract

1 The contractile action of the dipeptide carnosine (b-alanyl-L-histidine), active as a Zn·carnosine complex (Zn·Carn), was investigated in isolated rings of rabbit saphenous vein (RSV) and was found to be antagonized by the H 1 antagonist mepyramine. 2 Mepyramine-sensitive, histamine-induced contractures in RSV, were smaller (73+0.1%) and less well sustained than carnosine-induced contractures. In the radioligand binding assay, the e ect of carnosine can be described as a function of Zn·Carn concentration with an apparent logIC 50 of 75.61. This value is consistent with that obtained from the functional studies on RSV. 7 Histamine-induced contractures have an indomethacine-sensitive component (27.2+8.3% of control response), not apparent with carnosine-induced contractures. 8 Like histamine, carnosine evoked an H 2 -mediated (cimetidine-sensitive) relaxation in the presence of mepyramine, but was less potent (10.8+3.1% residual tension at 10 mM carnosine compared with 13.4+7.5% at 0.1 mM histamine). 9 Carnosine, like mepyramine, can`reveal' the H 2 -mediated relaxation of histamine providing further evidence that carnosine binds at the H 1 receptor. 10 We conclude that carnosine can act at the smooth muscle H 1 -receptor to provoke vasoconstriction and that it also has the potential to act at H 1 -receptors in CNS.

Carnosine protects brain microvascular endothelial cells against rotenone‐induced oxidative stress injury through histamine H1 and H2 receptors in vitro

“…Miller and O'Dowd have reported that, like histamine, carnosine directly activates smooth muscle histamine H 1 receptors to provoke vasoconstriction, but induces vascular relaxation through H 2 receptors . Ligand–receptor binding tests revealed that carnosine can bind directly to histamine H 1 receptors . Furthermore, an H 1 receptor antagonist has been reported to induce reactive oxygen species (ROS)‐dependent cytochrome c release and apoptosis .…”

“…27 Ligand-receptor binding tests revealed that carnosine can bind directly to histamine H 1 receptors. 28 Furthermore, an H 1 receptor antagonist has been reported to induce reactive oxygen species (ROS)-dependent cytochrome c release and apoptosis. 29 Conversely, intracellular increases in cAMP induce a protein kinase A-dependent inhibition of ROS production 30 and intracellular cAMP levels can be upregulated by activation of H 2 receptors.…”

Physiology and Pathophysiology of Carnosine

“…Given the potency of carnosine in the regulation of the vascular tone, it is thought that not only exogenously administered carnosine, but also endogenously available carnosine takes part in normal hemodynamic regulation. The formation in vivo of a zinc/carnosine complex and the involvement of histamine H 1 receptors appear to be involved in vascular smooth muscle contraction/relaxation (255,277). However, alternative vasoactive mechanisms of carnosine may be equally involved, such as the carnosine-histidine-histamine pathway (151), a NO/ cGMP mechanism (318), and the modulation of the autonomic nervous system (265).…”

Physiological Roles of Carnosine in Myocardial Function and Health

“…This effect was specific to carnosine, as its constituent amino acids were ineffective, and is considered to be attributed to the zinc/carnosine complex ( 105 , 106 ). Other mechanisms of the antihypertensive action of carnosine may be mediated via the histamine H1 receptors ( 107 ) and the carnosine-histamine-histidine pathway ( 108 ). A summary of the research investigating the effect of exogenous carnosine, and its constituent amino acids, on hemodynamic parameters in animal models is displayed in Table 3 .…”