. VR-1 receptor blockade attenuates the pressor response to capsaicin but has no effect on the pressor response to contraction in cats. Am J Physiol Heart Circ Physiol 288: H1867-H1873, 2005. First published November 24, 2004; doi:10.1152/ajpheart.00735.2004.-Vanilloid type 1 (VR-1) receptors are stimulated by capsaicin and hydrogen ions, the latter being a by-product of muscular contraction. We tested the hypothesis that activation of VR-1 receptors during static contraction contributes to the exercise pressor reflex. We established a dose of iodoresinaferatoxin (IRTX), a VR-1 receptor antagonist, that blocked the pressor response to capsaicin injected into the arterial supply of muscle. Specifically, in eight decerebrated cats, we compared pressor responses to capsaicin (10 g) injected into the right popliteal artery, which was subsequently injected with IRTX (100 g), with those to capsaicin injected into the left popliteal artery, which was not injected with IRTX. The pressor response to capsaicin injected into the right popliteal artery averaged 49 Ϯ 9 mmHg before IRTX and 9 Ϯ 2 mmHg after IRTX (P Ͻ 0.05). In contrast, the pressor response to capsaicin injected into the left popliteal artery averaged 46 Ϯ 10 mmHg "before" and 43 Ϯ 6 mmHg "after" (P Ͼ 0.05). We next determined whether VR-1 receptors mediated the pressor response to contraction of the triceps surae. During contraction without circulatory occlusion, the pressor response before IRTX (100 g) averaged 26 Ϯ 3 mmHg, whereas it averaged 22 Ϯ 3 mmHg (P Ͼ 0.05) after IRTX (n ϭ 8). In addition, during contraction with occlusion, the pressor responses averaged 35 Ϯ 3 mmHg before IRTX injection and 49 Ϯ 7 mmHg after IRTX injection (n ϭ 7). We conclude that VR-1 receptors play little role in evoking the exercise pressor reflex. exercise pressor reflex; group III and IV muscle afferents; sympathetic nervous system; reflex control of circulation DURING STATIC EXERCISE, mean arterial pressure, heart rate, and ventilation all increase. Two neural mechanisms evoke these effects, namely, central command (40) and the exercise pressor reflex (13,22). Central command involves the activation of cardiovascular and respiratory neuronal pools in the medulla to activate autonomic and ventilatory responses in a feed-forward manner. The exercise pressor reflex is evoked by the contraction-induced stimulation of group III and IV muscle afferents (21). Group III afferents are more mechanically sensitive than are group IV afferents, but both are stimulated by metabolites, such as lactic acid, bradykinin, cyclooxygenase products of arachidonic acid, and potassium ions (15,16,26,29,32).Capsaicin, the active ingredient in "hot" peppers, injected into the arterial supply of skeletal muscle reflexly increases mean arterial pressure, heart rate, and breathing (8, 41). Capsaicin stimulates the vanilloid receptor type 1 (VR-1), which also is responsive to increases in the concentration of hydrogen ions as well as increases in temperature (6). Hydrogen ions, dissociated from lactic a...