The effects of ODQ, an inhibitor of the activation of soluble guanylate cyclase on responses to NO donors, Acetylcholine (ACh) and Bradykinin (BK) were investigated in the pulmonary and systemic vascular beds of the rat. In these studies the administration of ODQ in a dose of 5 mg/kg iv attenuated vasodilator responses to 5 different NO donors without inhibiting responses to ACh and BK in the systemic and pulmonary vascular beds of the rat. Vasodilator responses to ACh were not inhibited by L-NAME or the TRPV4 antagonist GSK2193874 which attenuated vasodilator responses to the TRPV4 agonist GSK1016790A. ODQ did not inhibit vasodilator responses to agents reported to act in an NO independent manner or to vasoconstrictor agents and ODQ did not increase blood methemoglobin levels suggesting that off target effects were minimal. These results show that ODQ in a dose that inhibited NO donor mediated responses did not alter vasodilator responses to ACh in the pulmonary and systemic vascular beds and did not alter systemic vasodilator responses to BK. The present results indicate that decreases in pulmonary and systemic arterial pressures in response to ACh are not mediated by the activation of soluble guanylate cyclase or TRPV4 channels and that ODQ can be used to study the role of the activation of sGC in mediating vasodilator responses in the rat.
- soluble guanylate cyclase
- pulmonary vascular bed
- Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology