Capsaicin sensitive-sensory nerves and blood pressure regulation.
Capsaicin (8-methyl-N-vannillyl-6-nonenamide), via binding to the vanilloid receptor subtype 1 (VR1), stimulates a subpopulation of primary afferent neurons that project to cardiovascular and renal tissues. These capsaicin-sensitive primary afferent neurons are not only involved in the perception of somatic and visceral pain, but also have a "sensory-effector" function. Regarding the latter, these neurons release stored neuropeptides through a calcium-dependent mechanism via the binding of capsaicin to the VR1. A subset of capsaicin-sensitive sensory nerves contains calcitonin gene-related peptide (CGRP) and substance P (SP). These sensory neuropeptides are potent vasodilators and natriuretic/diuretic factors. Neonatal degeneration of capsaicin-sensitive sensory nerves has revealed novel mechanisms that underlie increased salt sensitivity and several experimental models of hypertension. These mechanisms are reviewed, which include insufficient suppression of plasma renin activity and plasma aldosterone levels subsequent to salt loading, enhancement of sympathoexcitatory response in the face of a salt challenge, activation of the endothelin-1 receptor, and impaired natriuretic response to salt loading in capsaicin-pretreated rats. These data indicate that sensory nerves counterbalance the prohypertensive effects of several neuro-hormonal systems to maintain normal blood pressure when challenged with salt loading. Mechanisms underlying pneumotoxicity and pulmonary hypertension as revealed by degeneration of capsaicin-sensitive nerves are also discussed. Finally, the therapeutic utilities of capsaicin, endogenous anandamide, and CGRP agonists are assessed.
Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI 48825, USA.
Prashant
P
Vaishnava
Donna H
DH
Wang
D000450:Aldosterone / Q000097:blood / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology* / Q000627:therapeutic use; D019332:Endothelin-1 / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy; D009475:Neurons, Afferent / Q000187:drug effects*; D012083:Renin / Q000097:blood / Q000378:metabolism; D012982:Sodium, Dietary / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects
D000959:Antihypertensive Agents; D019332:Endothelin-1; D012982:Sodium, Dietary; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D012083:Renin; D002211:Capsaicin