Function and regulation of the vanilloid receptor in rats fed a high salt diet.
OBJECTIVE
To test the hypothesis that activation of the vanilloid receptor (VR1) by high salt intake prevents salt-induced increases in arterial pressure via stimulation of release of calcitonin gene-related peptide (CGRP) from sensory nerves.


METHODS
Two protocols were used: (1) Wistar rats fed a normal sodium (NS) diet (0.5%) were given intravenous injection of vehicle, capsaicin (CAP), or capsazepine (CAPZ) (a selective VR1 antagonist) plus CAP; and (2) rats were pair-fed a high salt (HS) diet (4%) or NS diet for 3 days and used either for arterial cannulation for measurement of mean arterial pressure (MAP) or for collection of plasma and tissues. Radioimmunoassay, western blot, and fluorescent immunohistochemistry were used, respectively, to determine the plasma CGRP level, VR1 protein content, and co-localization of VR1 and CGRP.


RESULTS
CAP increased plasma CGRP levels and decreased MAP in rats fed a NS diet. CAPZ blocked CAP-induced increases in plasma CGRP levels and CAP-induced decreases in MAP. HS intake increased plasma CGRP levels by approximately 60% without changing the baseline MAP, but MAP was increased by CAPZ in HS-treated rats when compared with NS-treated rats. VR1 protein expression, which co-localized with CGRP, was increased in mesenteric resistance arteries and the renal medulla.


CONCLUSIONS
HS intake activates VR1, which plays a counter-regulatory role in preventing salt-induced increases in arterial pressure via stimulation of release of CGRP from sensory nerves. Increased VR1 expression in vascular and renal tissues may serve as a compensatory response to HS intake, which contributes to maintenance of normal salt sensitivity.
Li
Jianping
J
Department of Medicine and Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA.
Wang
Donna H
DH
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation / Q000502:physiology; D009475:Neurons, Afferent / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D011955:Receptors, Drug; D017673:Sodium Chloride, Dietary; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin