|dc.description.abstract||Glycine, a lipophilic non-essential amino acid biosynthesized from L-serine, L-alanine and L-threonine, plays a role in the biosynthesis of proteins, nucleotides, and glutathione. It is a neurotransmitter in the central nervous system and acts as a co-agonist at the N-methyl-D aspartate (NMDA) receptor. Oral administration of glycine is helpful in the management of schizophrenia. While long-term oral treatment with glycine is considered to exert a cardio-vascular protective role by overcoming endothelial dysfunction and oxidative stress, there are no systematic studies examining the cardiovascular effects of glycine. Recently, we showed that the precursor/metabolite of glycine, L-serine, evoked endothelium-dependent vasodilatation in rat mesenteric arterioles. Acute intravenous administration of L-serine produced a rapid, dose-dependent fall in blood pressure (BP) in both normotensive and hypertensive rats. These responses were abolished in the combined presence of the Ca2+ activated small and intermediate conductance K+ channel inhibitors, apamin and Tram-34/charybdotoxin. In contrast, intravenous administration of glycine evoked a fall in BP in normotensive Wistar-Kyoto (WKY) rats and an elevation of BP in spontaneously hypertensive rats (SHR), and in WKY rats subjected to chronic nitric oxide (NO) synthase (NOS) inhibition by oral treatment with NOS inhibitor, L-NAME (NG-nitro-L-arginine-methylester). Therefore, in vivo and in vitro studies were designed to address the mechanisms that contribute to the opposite effects of glycine in normotensive vs. hypertensive rats.
Experiments were performed using 14 weeks old male WKY, chronic L-NAME treated WKY and SHR strains. In vivo studies involved examination of changes in systemic hemodynamic parameters such as mean arterial pressure (MAP), heart rate (HR), total peripheral resistance (TPR) and cardiac output (CO) as well as regional hemodynamic parameters of changes in blood flow and vascular resistance in major organs/tissues following acute intravenous administration of glycine using fluorescent microsphere distribution technique. Parallel complementary in vitro studies were conducted to examine the effects of glycine on changes in basal tone and phenylephrine (PE) constricted tone in aortic rings with endothelium-intact and endothelium-denuded states after isolation from WKY and SHR strains. All these studies were conducted in the presence and absence of two NMDA antagonists, MK-801 and memantine.
In normotensive WKY rats, glycine (1 mmol/L) administration decreased MAP (P||en_US