Repeated cocaine administration reduces bradykinin-induced dilation of pial arterioles
| Autor: | J. R. Copeland, K. A. Willoughby, R. J. Police, E. F. Ellis |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Male
medicine.medical_specialty Physiology Vasodilator Agents Hemodynamics Prostaglandin Bradykinin Vasodilation 6-Ketoprostaglandin F1 alpha Asphyxia chemistry.chemical_compound Cocaine Physiology (medical) Internal medicine Animals Medicine Cyclooxygenase Inhibitors Aspirin biology business.industry Alanine Transaminase Acetylcholine Arterioles Endocrinology medicine.anatomical_structure chemistry Anesthesia Circulatory system biology.protein Pia Mater Rabbits Cyclooxygenase Corticosterone Cardiology and Cardiovascular Medicine business Blood vessel medicine.drug |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 271:H1576-H1583 |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | Using the acute cranial window technique in rabbits under surgical anesthesia, we tested the vasoactivity of acetylcholine (ACh, 10(-8)-10(-5) M), bradykinin (BK, 10(-8)-10(-5) M), and asphyxia (10% O2, 9% CO2, balance N2) after subchronic pretreatment with cocaine. After repeated administration of cocaine (20 mg.kg-1.day-1 sc x 7 days), the BK-induced dilation of pial arterioles was reduced by 51%. Previous work showed that BK produces dilation of pial arterioles by a cyclooxygenase-dependent oxygen radical-mediated mechanism and that in rabbits the BK-induced dilation is dependent on both vascular and nonvascular cyclooxygenase. Selective blockade of vascular cyclooxygenase, in addition to cocaine treatment, did not produce any greater inhibition of the BK-induced dilation. The dilation in response to ACh and asphyxia was unaltered by cocaine. Levels of cerebrospinal fluid prostaglandins suggest cocaine pretreatment may inhibit cerebral vascular prostaglandin production. Together, cerebrospinal fluid prostaglandin and vasoreactivity data indicate cocaine pretreatment selectively inhibits the vascular cyclooxygenase-dependent mechanism mediating the BK-induced dilation. This decreased response to BK in cocaine-treated rabbits may result from decreased oxygen radical production concomitant with decreased vascular prostaglandin production. Alternatively, oxygen radical scavenging may be increased after cocaine treatment. We speculate that cocaine-induced alterations in cerebrovascular function and metabolism may be related to the increased incidence of stroke reported to occur in human cocaine users. |
| Databáze: | OpenAIRE |
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