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1 Milton S. Hershey Medical Center, Division of Cardiology, Pennsylvania State University, College of Medicine, Hershey, PA, USA
2 Milton S. Hershey Medical Center, Division of Cardiology, Pennsylvania State University, College of Medicine, Hershey, PA, USA; Medicine, Lebanon VA Medical Center, Lebanon, PA, USA
* To whom correspondence should be addressed. E-mail: lsinoway{at}psu.edu.
The reflex cardiovascular responses to muscle contraction are mediated by both mechanical and metabolic stimulation of thin muscle afferent fibers. The metabolic stimulants and receptors involved in the responses are uncertain. Capsaicin depolarizes thin sensory afferent nerves that have vanilloid type 1 receptors (VR1). Among potential endogenous ligands of thin fibers, H+ has been suggested as a metabolite mediating the reflex muscle response as well as a potential stimulant of the VR1 receptor. It has also been suggested that acid-sensing ion channels (ASIC) mediates H+ evoking afferent nerve excitation. In this study we examined the roles of VR1 and ASIC in mediating the cardiovascular reflex responses to acid stimulation of muscle afferents in a rat model. In anesthetized rats, injections of capsaicin into the arterial blood supply of the triceps surae muscles evoked a biphasic response (n = 6). An initial fall in blood pressure (MAP: from baseline of 95.8 ± 9.5 to 70.4 ± 4.5 mmHg, P < 0.05 vs. baseline) was followed by an increase (MAP: 131.6 ± 11.3 mmHg, P < 0.05 vs. baseline). Anandamide (an endogenous substance that activates VR1 receptors) induced the same change in blood pressure as did capsaicin. Of note, the pressor component (but not depressor component) of the response was blocked by capsazepine (VR1 receptors antagonist) and by section of the afferent nerves. In another study performed in decerebrate rats (n = 8), H+ evoked a pressor response that was not blocked by capsazepine but was attenuated by amiloride (an ASIC blocker). Finally, in rats (n = 12) with pretreatment of resiniferatoxin to destroy muscle afferents containing VR1 receptors, both capsaicin and H+ responses were blunted. We conclude that H+ stimulates ASIC channels evoking the reflex response and that ASIC channels are likely to be frequently found on afferents containing VR1 receptors. The data also suggest that both VR1 and ASIC may play a role in the processing of muscle afferent signals evoking the muscle pressor reflex.
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