Vascular reactivity to angiotensin II alone or combined with a thromboxane A2 mimetic in the isolated perfused kidney of Lyon hypertensive rats

Abstract

The aim of this study was to evaluate whether thromboxane A2-prostaglandin H2 (TP) receptor activation potentiates the renal vasoconstrictor effect of Angiotensin II (Ang II) in genetically hypertensive rats of the Lyon strain (LH). Concentration-response curves (CRCs) to Ang II (5 pM to 10 nM), to the specific TP receptor agonist U46619 (7.5-960 nM) and to a mixture of Ang II + U46619 (fixed molar ratio of 1 : 9) were obtained in single-pass perfused kidneys isolated from 8 week-old LH and low blood pressure (LL) control rats. Baseline vascular resistance was significantly increased in LH compared to LL kidneys. Comparison of the CRCs obtained for Ang II and U46619 showed that, in both strains, Ang II was about 100 times more potent than U46619. For both drugs, the pD2 or slope values did not differ among the two strains. Co-activation of TP receptors, analyzed with the method of Pöch and Holzmann, tended to potentiate the effects of Ang II in LH but not in LL kidneys. In conclusion, isolated perfused kidneys of LH rat did not exhibit an increased vascular sensitivity to acute infusion of Ang II or U46619 compared to control LL ones. In addition, the results suggest that the interactions between Ang II and TP receptor agonist may differ among the two strains.