L-Serine lowers while glycine increases blood pressure in chronic L-NAME-treated and spontaneously hypertensive rats

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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.

Conclusion

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.

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