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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Pannirselvam, Malarvannan Triggle, Chris R. Verma, Subodh Anderson, Todd J. |
| Description | Author Affiliation: Pannirselvam M ( Department of Pharmacology and Therapeutics and Smooth Muscle Research group, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.) |
| Abstract | 1. Endothelium-dependent and -independent regulation of vascular tone in small mesenteric arteries (SMA) from control (db/db +/?) and diabetic (db/db -/-) mice was compared. 2. Phenylephrine-induced maximum contraction, but not sensitivity, of SMA in db/db -/- compared to db/db +/? was enhanced. 3. Acetylcholine (ACh), but not sodium nitroprusside (SNP), -induced relaxation was reduced in SMA from db/db -/- compared to db/db +/?. 4. ACh-induced relaxation of SMA was inhibited by a combination of N(omega)-nitro-L-arginine and indomethacin in db/db +/?, but not in db/db -/-. 5. Acute incubation of SMA with tetrahydrobiopterin (BH(4), 10 microM) and sepiapterin (100 microM) enhanced ACh-induced relaxation in SMA from db/db -/-, but not from db/db +/? 2,4-diamino-6-hydroxypyrimidine, an inhibitor of GTP cyclohydrolase I, (10 mM), impaired the sensitivity of SMA from db/db +/? to ACh, which was restored by co-incubation with BH(4) (10 microM). 6. BH(4) and superoxide dismutase (SOD, 150 u ml(-1)), either alone or in combination, had no effect on either ACh or SNP-induced relaxation in SMA from eNOS -/- mice. 7. Incubation of SMA with SOD (150 iu ml(-1)), catalase (200 iu ml(-1)) and L-arginine (1 mM) had no effect on ACh-induced relaxation of SMA. However, the combination of polyethylene glycol-SOD (200 iu ml(-1)) and catalase (80 u ml(-1)) improved the sensitivity of ACh-induced relaxation in db/db -/-, but not in db/db +/?. 8. These data suggest that increased production of superoxide anions and decreased availability of BH(4) result in an 'uncoupling' of nitric oxide synthase and endothelial dysfunction in SMA from db/db -/- mice. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 136 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2002-05-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Biopterin Analogs & Derivatives Pharmacokinetics Diabetes Mellitus, Type 2 Genetics Physiopathology Endothelium, Vascular Metabolism Mesenteric Arteries Receptors, Cell Surface Animals Biological Availability Dose-Response Relationship, Drug Drug Effects Mice Mice, Inbred C57BL Mice, Mutant Strains Receptors, Leptin Vasodilation Physiology Comparative Study Research Support, Non-U.S. Gov't Pharmacology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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