L-Serine lowers while glycine increases blood pressure in chronic L-NAME-treated and spontaneously hypertensive rats.
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.
Mishra
Ramesh C
RC
Department of Pharmacology, Department of Medicine, Royal University Hospital, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Tripathy
Saswati
S
Quest
Dale
D
Desai
Kaushik M
KM
Akhtar
Jawed
J
Dattani
Indravadan D
ID
Gopalakrishnan
Venkat
V
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
D004791:Enzyme Inhibitors; D024681:Potassium Channels, Calcium-Activated; D018999:Charybdotoxin; D001030:Apamin; D013912:Threonine; D012694:Serine; D005998:Glycine; D019331:NG-Nitroarginine Methyl Ester