The vanilloid receptor and hypertension

Authors: Donna H WANG


Mammalian transient receptor potential (TRP) channels consist of six related protein
sub-families that are involved in a variety of pathophysiological function, and
disease development. The TRPV1 channel, a member of the TRPV sub-family, is
identified by expression cloning using the “hot” pepper-derived vanilloid compound
capsaicin as a ligand. Therefore, TRPV1 is also referred as the vanilloid
receptor (VR1) or the capsaicin receptor. VR1 is mainly expressed in 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 VR1. The most studied
sensory neuropeptides are calcitonin gene-related peptide (CGRP) and substance
P (SP), which are potent vasodilators and natriuretic/diuretic factors. Recent evidence
using the model of neonatal degeneration of capsaicin-sensitive sensory
nerves revealed novel mechanisms that underlie increased salt sensitivity and
several experimental models of hypertension. These mechanisms 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 neurohormonal
systems to maintain normal blood pressure when challenged with salt
loading. The therapeutic utilities of vanilloid compounds, endogenous agonists,
and sensory neuropeptides are also discussed.

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