Blockade of the TP receptor attenuates the exercise pressor reflex in decerebrated rats with chronic femoral artery occlusion.

Anna K Leal, Jennifer L McCord, Hirotsugu Tsuchimochi, Marc P Kaufman

Index: Am. J. Physiol. Heart Circ. Physiol. 301(5) , H2140-6, (2011)

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Abstract

Cyclooxygenase metabolites stimulate or sensitize group III and IV muscle afferents, which comprise the sensory arm of the exercise pressor reflex. The thromboxane (TP) receptor binds several of these metabolites, whose concentrations in the muscle interstitium are increased by exercise under freely perfused conditions and even more so under ischemic conditions, which occur in peripheral artery disease. We showed that the exercise pressor reflex is greater in rats with simulated peripheral artery disease than in rats with freely perfused limbs. These findings prompted us to test the hypothesis that the TP receptor contributes to the exaggerated exercise pressor reflex occurring in a rat model of peripheral artery disease. We compared the cardiovascular responses to static contraction and stretch before and after femoral arterial injections of daltroban (80 μg), a TP receptor antagonist. We performed these experiments in decerebrate rats whose femoral arteries were ligated 72 h before the experiment (a model of simulated peripheral artery disease) and in control rats whose hindlimbs were freely perfused. Daltroban reduced the pressor response to static contraction in both freely perfused (n = 6; before: Δ12 ± 2 mmHg, after: Δ6 ± 2 mmHg, P = 0.024) and 72-h-ligated rats (n = 10; before: Δ25 ± 3 mmHg, after: Δ7 ± 4 mmHg, P = 0.001). Likewise, daltroban reduced the pressor response to stretch in the freely perfused group (n = 9; before: Δ30 ± 3 mmHg, after: Δ17 ± 3 mmHg, P < 0.0001) and in the ligated group (n = 11; before: Δ37 ± 5 mmHg, after: Δ23 ± 3 mmHg, P = 0.016). Intravenous injections of daltroban had no effect on the pressor response to contraction. We conclude that the TP receptor contributes to the pressor responses evoked by contraction and stretch in both freely perfused rats and rats with simulated peripheral artery disease.