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Role of COX-1 and -2 in prostanoid generation and modulation of angiotensin II responses

Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, Louisiana 70112

Submitted 3 April 2003 ; accepted in final form 7 July 2003

The role of cyclooxygenase (COX)-1 and -2 in prostanoid formation and modulation of pressor responses to ANG II was investigated in the pulmonary and systemic vascular beds in the rat. In the present study, selective COX-1 and -2 inhibitors attenuated increases in pulmonary arterial pressure and decreases in systemic arterial pressure in response to arachidonic acid but did not alter responses to PGE₁ or U-46619. The selective COX-1 and -2 inhibitors did not modify systemic pressor responses to injections or infusions of ANG II or pulmonary pressor responses to injections of the peptide. COX-2 inhibitors did not alter, whereas a COX-1 inhibitor depressed, arachidonic acid-induced platelet aggregation. These data provide evidence in support of the hypothesis that prostanoid synthesis occurs by way of the COX-1 and -2 pathways in the pulmonary and systemic vascular beds but that pressor responses to ANG II are not mediated or modulated by these pathways in the rat.

cyclooxygenase; prostanoid synthesis; pulmonary and systemic pressor responses; vasoconstrictor peptide; NS-398; SC-560; SC-236

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