Vasodilator and antihypertensive effects of l-serine
| dc.contributor.advisor | Gopalakrishnan, Venkat | en_US |
| dc.creator | Mishra, Ramesh Chandra | en_US |
| dc.date.accessioned | 2009-07-15T10:44:47Z | en_US |
| dc.date.accessioned | 2013-01-04T04:44:51Z | |
| dc.date.available | 2010-07-17T08:00:00Z | en_US |
| dc.date.available | 2013-01-04T04:44:51Z | |
| dc.date.created | 2009 | en_US |
| dc.date.issued | 2009 | en_US |
| dc.date.submitted | 2009 | en_US |
| dc.description.abstract | L-serine, a non-essential amino acid, plays a role in the biosynthesis of the amino acids, proteins, purine and pyrimidine nucleotides. It is important for the proper functioning of the nervous system. It has been considered in the treatment of patients with schizophrenia, depression, chronic fatigue syndrome and psychomotor retardation, and of the seizures encountered in patients with rare inborn errors of L-serine biosynthesis. However, there are no reports in the literature of the direct cardiovascular effects of L-serine. Using normotensive Sprague-Dawley rats, Sprague-Dawley rats rendered hypertensive by chronic treatment with the nitric oxide (NO) synthase inhibitior NG nitro L-arginine methyl ester (L-NAME) and spontaneously hypertensive rats (SHR), the present study examined the in vitro and in vivo effects of L-serine. In vitro studies focused on L-serine induced changes in phenylephrine constricted third order branches of rat mesenteric arterioles while the in vivo studies examined the effects of intravenous infusion of L-serine on mean arterial pressure (MAP) and heart rate (HR) in intact anaesthetized rats. L-serine (10 to 200 µmol/L) evoked concentration-dependent vasodilatation in phenylephrine constricted endothelium-intact, but not in endothelium-denuded, rat mesenteric arterioles. The vasodilator responses to L-serine were absent in the combined presence of apamin, a calcium activated small conductance potassium (SKCa) channel inhibitor, and TRAM-34, a calcium activated intermediate conductance potassium (IKCa) channel inhibitor, or ouabain, a sodium pump inhibitor and barium (Ba2+), an inward rectifying potassium (Kir) channel inhibitor, or when the vessels were depolarized by potassium chloride. The maximal vasodilatation response (Emax) to L-serine was higher in vessels from L-NAME treated rats (40%) than from control rats (20%). In anesthetized rats, L-serine evoked a rapid, reversible, dose-dependent fall in MAP (without a significant change in HR), which was more pronounced in L-NAME treated rats (> 60 mmHg) than in normotensive control rats (25 mmHg). The fall in MAP was inhibited (p | en_US |
| dc.identifier.uri | http://hdl.handle.net/10388/etd-07152009-104447 | en_US |
| dc.language.iso | en_US | en_US |
| dc.subject | Amino acids | en_US |
| dc.subject | Blood pressure | en_US |
| dc.subject | L-serine | en_US |
| dc.subject | Glycine | en_US |
| dc.subject | Vasodilation | en_US |
| dc.subject | Hypertension | en_US |
| dc.subject | Mean arterial pressure | en_US |
| dc.title | Vasodilator and antihypertensive effects of l-serine | en_US |
| dc.type.genre | Thesis | en_US |
| dc.type.material | text | en_US |
| thesis.degree.department | Pharmacology | en_US |
| thesis.degree.discipline | Pharmacology | en_US |
| thesis.degree.grantor | University of Saskatchewan | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) | en_US |