Mechanisms of potentiation of Angiotensin II-induced contractile response of isolated rat aorta by hydrogen peroxide and tert-butyryl hydroperoxide

• Published in: Indian journal of pharmacology 2009-05, Vol.41 (3), p.140-143
• Main Authors: Patel, R J, Patel, P D, Patel, M M, Patel, N J, Thyagarajan, B
• Format: Article
• Language: English
• Subjects: Angiotensin II receptor blockers; Aorta, Thoracic; Cell division; Contraction; Coronary vessels; Heart; Hydrogen; Hydrogen peroxide; Properties; Rodents
• ISSN: 0253-7613; 1998-3751
• DOI: 10.4103/0253-7613.55208

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. 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. 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. 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.