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Muscle pressor reflex: potential role of vanilloid type 1 receptor and acid-sensing ion channel

¹Division of Cardiology, Pennsylvania State College of Medicine, Milton S. Hershey Medical Center, Hershey 17033; and ²Lebanon Veterans Affairs Medical Center, Lebanon, Pennsylvania 17042

Submitted 9 April 2004 ; accepted in final form 19 June 2004

Reflex cardiovascular responses to muscle contraction are mediated by mechanical and metabolic stimulation of thin muscle afferent fibers. Metabolic stimulants and receptors involved in 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 VR₁. It has also been suggested that acid-sensing ion channels (ASIC) mediate H⁺, evoking afferent nerve excitation. We have examined the roles of VR₁ and ASIC in mediating 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 triceps surae muscles evoked a biphasic response (n = 6). An initial fall in mean arterial pressure (from baseline of 95.8 ± 9.5 to 70.4 ± 4.5 mmHg, P < 0.05 vs. baseline) was followed by an increase (to 131.6 ± 11.3 mmHg, P < 0.05 vs. baseline). Anandamide (an endogenous substance that activates VR₁) induced the same change in blood pressure as did capsaicin. The pressor (but not depressor) component of the response was blocked by capsazepine (a VR₁ antagonist) and section of afferent nerves. In decerebrate rats (n = 8), H⁺ evoked a pressor response that was not blocked by capsazepine but was attenuated by amiloride (an ASIC blocker). In rats (n = 12) pretreated with resiniferatoxin to destroy muscle afferents containing VR₁, capsaicin and H⁺ responses were blunted. We conclude that H⁺ stimulates ASIC, evoking the reflex response, and that ASIC are likely to be frequently found on afferents containing VR₁. The data also suggest that VR₁ and ASIC may play a role in processing of muscle afferent signals, evoking the muscle pressor reflex.

hydrogen ion; muscle afferent fibers

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