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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Stevens, E. J. Tomlinson, D. R. |
| Description | Author Affiliation: Stevens EJ ( William Harvey Research Institute, Department of Pharmacology, Queen Mary and Westfield College, London.) |
| Abstract | 1. The effects of the non-selective endothelin (ET) receptor (ETA/ETB) antagonist, bosentan, on sciatic nerve dysfunction in experimental diabetes were investigated. 2. Rats with 5-6 weeks untreated streptozotocin-diabetes exhibited characteristic slowed motor nerve conduction velocity (mean +/- s.d., 36.6 +/- 3.4 m s-1) and nerve laser Doppler flux (197 +/- 64 arbitrary units) compared to age-matched control animals (42.7 +/- 2.4 m s-1 and 398 +/- 77 arbitrary units, respectively). Preventative treatment of diabetic rats with bosentan at 100 mg kg-1 day-1 p.o. attenuated both these deficits (39.7 +/- 3.0 m s-1 and 305 +/- 56 arbitrary units, respectively) without affecting mean arterial pressure. 3. In control and untreated diabetic rats, ET-1, 1 nmol kg-1 i.v., caused an initial hypotension (duration, 30 +/- 13 and 26 +/- 9 s, respectively; change in mean arterial pressure, -27 +/- 13 and -25 +/- 7 mmHg, respectively) followed by prolonged hypertension (change in mean arterial pressure, 52 +/- 18 and 31 +/- 5 mmHg, respectively). Effectiveness of the chronic bosentan treatment was demonstrated by inhibition of the hypotensive response to ET-1 in treated diabetic rats (duration, 5 +/- 2 s; change in mean arterial pressure, -4 +/- 2 mmHg) although the hypertension was unaltered (change in mean arterial pressure, 32 +/- 9 mmHg). 4. Acute i.v. administration of 10 mg kg-1 bosentan caused variable and transient rises in nerve laser Doppler flux in control (78 +/- 63 arbitrary units) and untreated diabetic rats (93 +/- 77 arbitrary units). Acute bosentan blocked the hypotensive response to subsequent ET-1 administration and attenuated the later hypertension (change in mean arterial pressure, 21 +/-9 mmHg in control, 29 +/- 10 mmHg in diabetic).5. Our results indicate that oral treatment of diabetic rats with an ET receptor antagonist can improves ciatic nerve perfusion and conduction, suggesting that the vasoconstrictor action of endogenous ET may contribute to peripheral nerve dysfunction in experimental diabetes. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 115 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1995-05-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Diabetes Mellitus, Experimental Physiopathology Endothelin Receptor Antagonists Endothelins Pharmacology Sciatic Nerve Drug Effects Sulfonamides Animals Blood Glucose Blood Pressure Body Weight Disease Models, Animal Administration & Dosage Heart Rate Injections, Intravenous Laser-Doppler Flowmetry Neural Conduction Rats, Wistar Blood Supply Physiology Streptozocin Toxicity Comparative Study Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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