title: L-Serine lowers while glycine increases blood pressure in chronic L-NAME-treated and spontaneously hypertensive rats.
abstract: OBJECTIVE
  To determine the acute hemodynamic effects of the nonessential amino acid, glycine, and its precursor, L-serine, in normotensive and hypertensive rats.
  
  
  METHODS
  Changes in mean arterial pressure and heart rate evoked by comparable intravenously administered doses (0.3-3.0 mmol/kg) of L-serine, D-serine and glycine were examined in anaesthetized normotensive 14-week-old male Sprague-Dawley, Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats and WKY rats subjected to chronic nitric oxide synthase inhibition by treatment with NG nitro L-arginine methyl ester (0.7 mg/ml in drinking water for 5 days).
  
  
  RESULTS
  L-Serine evoked a greater maximal fall in mean arterial pressure [L-serine vs. D-serine in Sprague-Dawley rats, mean +/- standard error of the mean values (mmHg): 30 +/- 3 vs. 20 +/- 5, P < 0.05; in control WKY rats: 46 +/- 3 vs. 30 +/- 4, P < 0.05; in NG nitro L-arginine methyl ester-treated WKY rats: 93 +/- 6 vs. 41 +/- 5, P < 0.01; in spontaneously hypertensive rats: 81 +/- 7 vs. 39 +/- 5 P < 0.01]. The effects of L-serine were significantly reduced in rats pretreated with a combination of apamin and charybdotoxin, inhibitors of the small conductance and intermediate conductance calcium-activated potassium (KCa) channels. Glycine elicited a dose-dependent fall in mean arterial pressure in normotensive WKY rats (25 +/- 4; P < 0.01) and evoked pressor responses in both spontaneously hypertensive rats (29 +/- 3; P < 0.01) and NG nitro L-arginine methyl ester-pretreated hypertensive WKY (39 +/- 5; P < 0.01) rats. Both the depressor and pressor responses to glycine were abolished by pretreatment with the N-methyl D-aspartate receptor antagonist, MK-801.
  
  
  CONCLUSIONS
  The profound stereo-selective antihypertensive effect of L-serine is neither mediated nor mimicked by glycine. It does not require N-methyl D-aspartate receptor activation by glycine but likely involves activation of endothelial KCa channels. L-Serine is a potential antihypertensive agent.
authors.affiliation: Department of Pharmacology, Department of Medicine, Royal University Hospital, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Mishra
authors.forename: Saswati
authors.initials: S
authors.lastname: Tripathy
authors.forename: Dale
authors.initials: D
authors.lastname: Quest
authors.forename: Kaushik M
authors.initials: KM
authors.lastname: Desai
authors.forename: Jawed
authors.initials: J
authors.lastname: Akhtar
authors.forename: Indravadan D
authors.initials: ID
authors.lastname: Dattani
authors.forename: Venkat
authors.initials: V
authors.lastname: Gopalakrishnan
mesh_terms: D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology*; D018999:Charybdotoxin / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors; D005998:Glycine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000494:pharmacology*; D013912:Threonine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D024681:Potassium Channels, Calcium-Activated; D018999:Charybdotoxin; D001030:Apamin; D013912:Threonine; D012694:Serine; D005998:Glycine; D019331:NG-Nitroarginine Methyl Ester