The exercise pressor reflex is evoked by both mechanical and metabolic stimuli. Tendon stretch does not increase muscle metabolism and therefore is used to investigate the mechanical component of the exercise pressor reflex. An important assumption underlying the use of tendon stretch to study the mechanical component of the exercise pressor reflex is that stretch stimulates the same group III mechanosensitive muscle afferents as does static contraction. We have tested the veracity of this assumption in decerebrated cats by comparing the responses of group III and IV muscle afferents to tendon stretch with those to static contraction. The tension-time indexes as well as the peak tension development for both maneuvers did not significantly differ. We found that static contraction of the triceps surae muscles stimulated 18 of 30 group III afferents and 8 of 11 group IV afferents. Similarly, tendon stretch stimulated 14 of 30 group III afferents and 3 of 11 group IV afferents. However, of the 18 group III afferents that responded to static contraction and the 14 group III afferents that responded to tendon stretch, only 7 responded to both stimuli. On average, the conduction velocities of the 18 group III afferents that responded to static contraction (11.6 +/- 1.6 m/s) were significantly slower (P = 0.03) than those of the 14 group III afferents that responded to tendon stretch (16.7 +/- 1.5 m/s). We have concluded that tendon stretch stimulated a different population of group III mechanosensitive muscle afferents than did static contraction. Although there is some overlap between the two populations of group III mechanosensitive afferents, it is not large, comprising less than half of the group III afferents responding to static contraction.

The mode of synaptic transmission in the vestibular periphery, between type I hair cells and their associated calyx terminal, has been the subject of much debate. The close and extensive apposition of pre- and post-synaptic elements has led some to suggest potassium (K(+)) accumulates in the intercellular space and even plays a role in synaptic transmission. During patch clamp recordings from isolated and embedded hair cells in a semi-intact preparation of the mouse cristae, we noted marked differences in whole-cell currents. Embedded type I hair cells show a prominent droop during steady-state activation as well as a dramatic collapse in tail currents. Responses to a depolarizing voltage step (-124 to +16 mV) in embedded, but not isolated, hair cells resulted in a >40 mV shift of the K(+) equilibrium potential and a rise in effective K(+) concentration (>50 mM) in the intercellular space. Together these data suggest K(+) accumulation in the intercellular space accounts for the different responses in isolated and embedded type I hair cells. To test this notion, we exposed the preparation to hyperosmotic solutions to enlarge the intercellular space. As predicted, the K(+) accumulation effects were reduced; however, a fit of our data with a classic diffusion model suggested K(+) permeability, rather than the intercellular space, had been altered by the hyperosmotic change. These results support the notion that under depolarizing conditions substantial K(+) accumulation occurs in the space between type I hair cells and calyx. The extent of K(+) accumulation during normal synaptic transmission, however, remains to be determined.

Cyclooxygenase products accumulate in statically contracting muscles to stimulate group III and IV afferents. The role played by these products in stimulating thin fiber muscle afferents during dynamic exercise is unknown. Therefore, in decerebrated cats, we recorded the responses of 17 group III and 12 group IV triceps surae muscle afferents to dynamic exercise, evoked by stimulation of the mesencephalic locomotor region. Each afferent was tested while the muscles were freely perfused and while the circulation to the muscles was occluded. The increases in group III and IV afferent activity during dynamic exercise while the circulation to the muscles was occluded were greater than those during exercise while the muscles were freely perfused ( P < 0.01). Indomethacin (5 mg/kg iv), a cyclooxygenase blocker, reduced the responses to dynamic exercise of the group III afferents by 42% when the circulation to the triceps surae muscles was occluded ( P < 0.001) and by 29% when the circulation was not occluded ( P = 0.004). Likewise, indomethacin reduced the responses to dynamic exercise of group IV afferents by 34% when the circulation was occluded ( P < 0.001) and by 18% when the circulation was not occluded ( P = 0.026). Before indomethacin, the activity of the group IV, but not group III, afferents was significantly higher during postexercise circulatory occlusion than during rest ( P < 0.05). After indomethacin, however, group IV activity during postexercise circulatory occlusion was not significantly different from group IV activity during rest. Our data suggest that cyclooxygenase products play a role both in sensitizing group III and IV afferents during exercise and in stimulating group IV afferents during postexercise circulatory occlusion.

Although thin fibre muscle afferents possess acid sensing ion channels (ASICs), their contribution to the exercise pressor reflex is not known. This lack of information is partly attributable to the fact that there is no known selective in vivo antagonist for ASICs. Although amiloride has been shown to antagonize ASICs, it also has been shown to antagonize voltage-gated sodium channels, thereby impairing impulse conduction in sensory nerves. Our aim was to test the hypothesis that lactic acid accumulation in exercising muscle acted on ASICs located on thin fibre muscle afferents to evoke the metabolic component of the exercise pressor reflex. To test this hypothesis, we determined in decerebrate cats if amiloride attenuated the pressor and cardioaccelerator responses to static contraction, to tendon stretch and to arterial injections of lactic acid and capsaicin. We found a dose of amiloride (0.5 μg kg −1 ; I.A.) that attenuated the pressor and cardioaccelerator responses to both contraction and lactic acid injection, but had no effect on the responses to stretch and capsaicin. A higher dose of amiloride (5 μg kg −1 , I.A.) not only blocked the pressor and cardioaccelerator responses to lactic acid and contraction, but also attenuated the responses to stretch and to capsaicin, manoeuvers in which ASICs probably play no significant role. In addition, we found that the low dose of amiloride (0.5 μg kg −1 ) had no effect on the responses of muscle spindles to tendon stretch and to succinylcholine, whereas the high dose (5 μg kg −1 ) attenuated the responses to both. Our data suggest the low dose of amiloride used in our experiments selectively blocked ASICs, whereas the high dose blocked ASICs and impulse conduction in muscle afferents. We conclude that ASICs play a role in the metabolic component of the exercise pressor reflex.

. 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...