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Am J Physiol Heart Circ Physiol (October 16, 2003). doi:10.1152/ajpheart.00477.2003
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Submitted on May 22, 2003
Accepted on October 14, 2003

Interaction between Prostanoids and Nitric Oxide in Regulation of Systemic, Pulmonary and Coronary Vascular Tone in Exercising Swine

Daphne Merkus1*, Birgit Houweling1, Alisina Zarbanoui1, and Dirk J Duncker1

1 Experimental Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

* To whom correspondence should be addressed. E-mail: d.merkus{at}erasmusmc.nl.

Prostacyclin and 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 cyclo-oxygenase (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), in the absence and presence of NO synthase inhibition with N{omega}-nitro-Larginine (NLA, 20 mg/kg iv). COX-inhibition produced systemic vasoconstriction at rest, that waned during exercise. The systemic vasoconstriction by COX-inhibition was enhanced after NLA, 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 NLA. In contrast, COXinhibition 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 NLA. 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 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 bed.




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