Muscle pressor reflex: potential role of vanilloid type 1 receptor and acid-sensing ion channel.
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.
Li
Jianhua
J
Division of Cardiology, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 Univ. Dr., Hershey, PA 17033, USA. jzl10@psu.edu
Maile
Michael D
MD
Sinoway
Adam N
AN
Sinoway
Lawrence I
LI
D062565:Acid Sensing Ion Channels; D000818:Animals; D001095:Arachidonic Acids; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin; D004224:Diterpenes / Q000494:pharmacology; D063388:Endocannabinoids; D006339:Heart Rate / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D019344:Lactic Acid / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000502:physiology*; D050916:TRPV Cation Channels
D062565:Acid Sensing Ion Channels; D001095:Arachidonic Acids; D004224:Diterpenes; D063388:Endocannabinoids; D007473:Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D053284:Polyunsaturated Alkamides; D015222:Sodium Channels; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D019344:Lactic Acid; C024353:resiniferatoxin; D002211:Capsaicin; C078814:anandamide