Prostacyclin and nitric oxide (NO) are produced by the endothelium in response to physical forces such as shear stress. Consequently, both NO and prostacyclin may increase during exercise and contribute to metabolic vasodilation. Conversely, NO has been hypothesized to inhibit prostacyclin production. We therefore investigated the effect of cyclooxygenase (COX) inhibition on exercise-induced vasodilation of the porcine systemic, pulmonary, and coronary beds before and after inhibition of NO production. Swine were studied at rest and during treadmill exercise at 1-5 km/h, before and after COX inhibition with indomethacin (10 mg/kg iv), and in the absence and presence of NO synthase inhibition with N(omega)-nitro-l-arginine (l-NNA; 20 mg/kg iv). COX inhibition produced systemic vasoconstriction at rest, which waned during exercise. The systemic vasoconstriction by COX inhibition was enhanced after l-NNA, particularly at rest. In the coronary circulation, COX inhibition also resulted in vasoconstriction at rest and during exercise. However, vasoconstriction was not modified by pretreatment with l-NNA. In contrast, COX inhibition had no effect on the pulmonary circulation, either at rest or during exercise. Moreover, a prostanoid influence in the pulmonary circulation could not be detected after l-NNA. In conclusion, endogenous prostanoids contribute importantly to systemic and coronary tone in awake swine at rest but are not mandatory for exercise-induced vasodilation in these beds. Endogenous prostanoids are not mandatory for the regulation of pulmonary resistance vessel tone. Finally, NO blunts the contribution of prostanoids to vascular tone regulation in the systemic but not in the coronary and pulmonary beds.

Animals, Blood Pressure/drug effects/physiology, Cardiac Output/drug effects/physiology, Coronary Circulation/drug effects/*physiology, Cyclooxygenase Inhibitors/pharmacology, Epoprostenol/*metabolism, Exertion/*physiology, Female, Heart Rate/drug effects/physiology, Indomethacin/pharmacology, Male, Microcirculation/drug effects/physiology, Nitric Oxide Synthase Type III, Nitric Oxide Synthase/antagonists & inhibitors/metabolism, Nitric Oxide/*metabolism, Pulmonary Circulation/drug effects/*physiology, Research Support, Non-U.S. Gov't, Sus scrofa,
American Journal of Physiology - Heart and Circulatory Physiology
Erasmus MC: University Medical Center Rotterdam

Merkus, D, Houweling, B, Zarbanoui, A, & Duncker, D.J.G.M. (2004). Interaction between prostanoids and nitric oxide in regulation of systemic, pulmonary, and coronary vascular tone in exercising swine. American Journal of Physiology - Heart and Circulatory Physiology, 1114–1123. doi:10.1152/ajpheart.00477.2003