Effects of glutamate and zinc ions on the contractility of vascular smooth muscle preparations

Abstract

It was shown in this study that isolated porcine coronary arteries (PCA) contracted by depolarization with high Ko or by histamine are dose-dependently relaxed by glutamic acid, aspartic acid, N-methyl-asparate (NMDA) and γ-aminobutyric acid (GABA). Zn 2+ was also shown to relax dose-dependently PCA contractions induced by 50 mM KCl with an ED 50 value of about 1.5 mM and to inhibit dose-dependently histamine-induced contractions, shifting ED 50 values from 6µM to 40 µM, not affecting however corresponding cumulative concentration-response (CCR) curves established for acetylcholine-induced contractions. Furthermore, since Zn 2+ ions are co-localized in many glutamatergic synapses of the central nervous system, it has been postulated in analogy to glutamate neurotoxicity that perturbations of the synaptic zinc concentrations might be a triggering factor in several cerebral diseases, such as ischemic strokes and sustained seizures. Unfortunately, little is known so far about effects of glutamate and zinc ions on the vascular tone. Although the nature of the glutamatergic receptors occurring in the blood vessels investigated in this study remains unclear, the results suggest that glutamate and Zn2+ ions interact with voltage-gated as well with ligand-operated Ca-channels. An interesting aspect might be the putative role of glutamate and zinc as long-term toxic agents in the early steps of the pathomechanisms leading to degenerative vascular lesions.