Published Online
on August 4, 2003

A more recent version of this article appeared on August 19, 2003

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Submitted on March 7, 2003
Revised on April 24, 2003
Accepted on April 25, 2003

Role of Cyclooxygenase-2 in the Generation of Vasoactive Prostanoids in the Rat Pulmonary and Systemic Vascular Beds

Syed R. Baber BS, Hunter C. Champion MD, PhD, Trinity J. Bivalacqua BS, Albert L. Hyman MD, and Philip J. Kadowitz PhD^*

From the Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, La.

^* To whom correspondence should be addressed. E-mail: pkadowi{at}tulane.edu.

Background--Prostanoid synthesis by the cyclooxygenase (COX)-2 pathway plays an important role in inflammation, and recent studies have shown the presence of COX-2 in the normal rat lung. However, the role of COX-2 in the generation of vasoactive prostanoids in the rat is uncertain. In the present study, the hypothesis that synthesis of vasoactive prostanoids via the COX-2 pathway can alter pulmonary and systemic vascular resistance was investigated, and the effects of selective COX-2 inhibitors on pulmonary and systemic responses to the prostanoid precursor arachidonic acid were examined in the anesthetized rat with a recently developed right-heart catheterization technique.

Methods and Results--Injections of arachidonic acid caused dose-related increases in pulmonary vascular resistance and decreases in systemic vascular resistance. These responses were attenuated by selective COX-2 inhibitors and a selective COX-1 inhibitor, whereas responses to exogenous prostanoids were not altered. Nimesulide or NS-398 did not alter arachidonic acid-induced platelet aggregation in rat platelet-rich plasma. Western blot analysis and immunostaining showed the expression of both COX isoforms in the rat lung.

Conclusions--The results of these experiments suggest that arachidonic acid is converted into vasoactive prostanoids by the COX-2 and COX-1 pathway in the pulmonary and peripheral vascular beds in the rat and that TXA₂ is a major prostanoid formed in the normal rat lung.

Key words: prostaglandins • thromboxane • rat • lung • enzymes

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