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Effects of aspirin, nimesulide, and SC-560 on vasopressin-induced contraction of human gastroepiploic artery and saphenous vein*

Aldasoro, Martin MD; Mauricio, Maria D. PhD; Serna, Eva PhD; Cortina, Belen PhD; Segarra, Gloria PhD; Medina, Pascual PhD; Vila, José M. PhD; Flor, Blas MD; Lluch, Salvador MD

doi: 10.1097/01.CCM.0000292155.06797.62
Laboratory Investigations

Objective: The present experiments were designed to evaluate differences in the effects of cyclooxygenase (COX)-1 and COX-2 inhibition on contractile responses of human gastroepiploic artery and saphenous vein elicited by vasopressin.

Design: Laboratory investigation.

Setting: University laboratory.

Subjects: Rings of human gastroepiploic artery were obtained from 32 patients undergoing gastrectomy, and rings of saphenous vein were obtained from 30 patients undergoing coronary artery bypass surgery.

Interventions: The rings were suspended in organ baths for isometric recording of tension. We studied the responses to vasopressin in the absence and in the presence of either the 1-receptor">vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)AVP or the COX inhibitors aspirin, nimesulide, or SC-560.

Measurements and Main Results: Vasopressin (10−11–10−6 mol/L) produced concentration-dependent contractions with an EC50 value of 4.3 × 10−10 mol/L for gastroepiploic artery and 3.4 × 10−8 mol/L for saphenous vein. The 1-receptor">vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)AVP (10−7 mol/L) induced significant shifts (p < .001) of the control curves to the right. The COX-1 and COX-2 inhibitor aspirin (10−6–10−5 mol/L) and the COX-2 inhibitor nimesulide (10−6 mol/L) induced leftward shifts of the concentration-response curve for vasopressin in gastroepiploic artery. Lower concentrations of aspirin or the COX-1 inhibitor SC-560 (10−8 mol/L) did not affect the responses of gastroepiploic artery. COX-1 or COX-2 inhibition did not modify the contraction of saphenous vein to vasopressin.

Conclusion: The results provide functional evidence that aspirin at high concentrations and the COX-2 selective inhibitor nimesulide potentiate the contractile response of gastroepiploic artery to vasopressin, thus suggesting the release of relaxant prostaglandins by the peptide. However, contractions of human saphenous vein were unaffected by COX inhibition, indicating that vasopressin does not stimulate the release of prostanoids. The amplifying effect of aspirin on vasopressin-induced contraction may contribute to early graft failure when the gastroepiploic artery is used as a coronary artery bypass graft.

From the Departamento de Fisiología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain (MA, MDM, ES, BC, GS, PM, JMV, SL); and Servicio de Cirugía General y Digestiva, Hospital Clínico Universitario, Valencia, Spain (BF).

The authors have not disclosed any potential conflicts of interest.

Supported, in part, by Generalitat Valenciana, Fondo de Investigaciones Sanitarias and Ministerio de Ciencia y Tecnología.

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© 2008 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins