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      Differential Vasoreactivity to the Thromboxane A 2 Mimic U-46619 of Collateral and Normal Peripheral Blood Vessels in in situ Perfused Rat Hindquarters

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          Abstract

          In situ perfusion of rat hindquarters was performed through both iliac arteries. Perfusion pressures were measured concomitantly in the normal vascular bed and in the ligation-induced collateral bed of the left and right hindleg, respectively. An increased vasoconstrictive response of the collateral versus normal blood vessels was found after bolus injections of increasing concentrations of the thromboxane A<sub>2</sub> (TXA<sub>2</sub>) mimic U-46619. This increased reactivity was related to a difference in vascular structure and in receptor-mediated sensitivity. The vasoconstrictive effect of U-46619 was dose-dependently inhibited by the combined TXA<sub>2 </sub>synthetase inhibitor-TXA<sub>2</sub>/prostaglandin endoperoxide (PGH2) receptor antagonist ridogrel and the single TXA<sub>2</sub>/PGH<sub>2</sub> receptor antagonist sulotroban. Selective blockade of α<sub>1</sub>- α<sub>2</sub>,-, β<sub>1</sub>- β<sub>2</sub> and S<sub>2</sub>-receptors, cyclooxygenase inhibition, TXA<sub>2</sub> synthesis inhibition, amine depletion and amine uptake blockade had no influence on the vasoconstrictive action of U-46619. Ca<sup>2+</sup> entry blockade by flunarizine and nifedipine significantly reduced the vasoconstriction. This study shows that (1) rat peripheral collaterals in relation to normal arterial blood vessels are significantly more reactive to TXA<sub>2</sub>; (2) the vasoconstrictive effect of U-46619 is mediated predominantly by TXA<sub>2</sub>/PGH<sub>2</sub> receptors; (3) the activation of these receptors elicits indirectly transmembrane Ca<sup>2+</sup> entry to trigger vasoconstriction.

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          Author and article information

          Journal
          JVR
          J Vasc Res
          10.1159/issn.1018-1172
          Journal of Vascular Research
          S. Karger AG
          1018-1172
          1423-0135
          1989
          1989
          23 September 2008
          : 26
          : 3
          : 165-176
          Affiliations
          Department of Haematology, Janssen Research Foundation, Beerse, Belgium
          Article
          158765 Blood Vessels 1989;26:165–176
          10.1159/000158765
          © 1989 S. Karger AG, Basel

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          Page count
          Pages: 12
          Categories
          Research Paper

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