| RESEARCH ARTICLE
|Year : 2009 | Volume
| Issue : 3 | Page : 140-143
Mechanisms of potentiation of Angiotensin II-induced contractile response of isolated rat aorta by hydrogen peroxide and tert-butyryl hydroperoxide
RJ Patel1, PD Patel1, MM Patel1, NJ Patel1, B Thyagarajan2
1 Department of Pharmacology, Shree S. K. Patel College of Pharmaceutical Education and Research, Ganpat Vidyanagar, Kherva-382711, Gujarat, India
2 Department of Pharmacology and Physiology, UMDNJ - New Jersey Medical School, Medical Sciences Building, 185 S, Orange Avenue, Newark, NJ 07103
Objective: To study the mechanism involved in hydrogen peroxide (H 2 O 2 ) or tert-butyl hydroperoxide (t-BHP)-induced potentiation of the Ang II-mediated contraction of isolated rat thoracic aorta.
Materials and Methods: Thoracic aorta was isolated from the Sprauge dawley rats (300-320 gm), cut spirally and response to Ang II (5 ´ 10 -8 M) was taken in the absence and presence of H 2 O 2 (10 -6 M) and t-BHP (10 -5 M). To explore the probable mechanism of H 2 O 2 and t-BHP-induced potentiation of Ang II-mediated contractile response, different blockers such as losartan (AT 1 receptor blocker; 1 µM), catalase (H 2 O 2 scavenger; 500 U/ml), lercanidipine (L-type calcium channel blocker; 1 µM), geinistein (tyrosine kinase inhibitor; 100 µM), and indomethacin (cyclo-oxygenase inhibitor; 10 µM) were used.
Results: In spiral preparation of rat thoracic aorta, H 2 O 2 (10 -6 M) and t-BHP (10 -5 M) did not produce the contraction as such. However, when they are added simultaneously with Ang II (5 ´ 10 -8 M), they potentiated the contractile response of the Ang II. Catalase (500 U/ml) partially antagonized the Ang-II-induced contraction, as well as antagonized the potentiation induced by H 2 O 2 . Losartan (1 µM) and lercanidipine (1 µM) antagonized the Ang II-induced contractile response without affecting H 2 O 2 (10 -6 M)-mediated potentiation. Geinistein (100 µM) antagonized H 2 O 2 (10 -6 M)-mediated potentiation, but it slightly decreased the Ang II response. Losartan (1 µM) and lercanidipine (1 µM) and Geinistein (100 µM) antagonized the Ang II-induced contractile response but not t-BHP-mediated potentiation. Indomethacin antagonized t-BHP-mediated potentiation without affecting much of Ang II response.
Conclusion: From the above-mentioned results, we can reasonably conclude that H 2 O 2 and t-BHP potentiated the contraction induced by the Ang II. H 2 O 2 -induced potentiation of Ang II response may be mediated through tyrosine kinase activation and t-BHP through the activation of cyclo-oxygenase enzyme.
R J Patel
Department of Pharmacology, Shree S. K. Patel College of Pharmaceutical Education and Research, Ganpat Vidyanagar, Kherva-382711, Gujarat, India
Source of Support: None, Conflict of Interest: None
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