Abstract
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 x 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 muM), catalase (H(2)O(2) scavenger; 500 U/ml), lercanidipine (L-type calcium channel blocker; 1 muM), geinistein (tyrosine kinase inhibitor; 100 muM), and indomethacin (cyclo-oxygenase inhibitor; 10 muM) 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 x 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 muM) and lercanidipine (1 muM) antagonized the Ang II-induced contractile response without affecting H(2)O(2) (10(-6)M)-mediated potentiation. Geinistein (100 muM) antagonized H(2)O(2) (10(-6)M)-mediated potentiation, but it slightly decreased the Ang II response. Losartan (1 muM) and lercanidipine (1 muM) and Geinistein (100 muM) 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.