Role of renin-angiotensin-aldosterone system in salt-sensitive hypertension induced by sensory denervation

Abstract

To define the role of the renin-angiotensin-aldosterone system in a novel salt-sensitive model, neonatal Wistar rats were given capsaicin (50 mg/kg sc) on the first and second days of life. After weaning, male rats were divided into the following six groups and treated for 3 wk with: control + normal sodium diet (CON-NS), CON + high-sodium diet (CON-HS), CON + HS + spironolactone (50 mg x kg(-1) x day(-1), CON-HS-SP), capsaicin pretreatment + NS (CAP-NS), CAP-HS, and CAP-HS-SP. Radioimmunoassay shows that plasma renin activity (PRA) and plasma aldosterone level (PAL) were suppressed by HS, but they were higher in CAP-HS than in CON-HS and CON-HS-SP (P < 0.05). Both tail-cuff systolic blood pressure and mean arterial pressure were higher in CAP-HS than in all other groups (P < 0.05). Urine water and sodium excretion were increased with HS intake, but they were lower in CAP-HS than in CON-HS (P < 0.05). Western blot did not detect differences in adrenal AT1 receptor content. Therefore, insufficiently suppressed PRA and PAL in response to HS intake by sensory denervation may contribute to increased salt sensitivity and account for effectiveness of spironolactone in lowering blood pressure in this model.

Enhanced salt sensitivity following shRNA silencing of neuronal TRPV1 in rat spinal cord

“…These data show that selective knockdown of neuronal TRPV1 enhances prohypertensive effects induced by salt loading and that pressor effects of TRPV1 shRNA may be mediated, at least in part, by enhancement of the sympatho-excitatory response. We have previously shown that neonatal degeneration of TRPV1-expressing sensory nerves increased salt sensitivity of arterial pressure as these rats grew into adulthood [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] . However, the systemic sensory denervation used in these previous studies precluded us from making conclusions about whether the observed effect was due to the removal of TRPV1 or other proteins co-expressed in the same nerves innervating any specific organs or tissues [21,22] .…”

“…Thus, defining the role of TRPV1-positive sensory nerves in the regulation of blood pressure and salt sensitivity will be useful. We have shown previously that the degeneration of TRPV1-expressing sensory nerves throughout the neonatal body by subcutaneous injection of capsaicin, a selective TRPV1 agonist, leads to increased salt sensitivity of arterial pressure, indicating that TRPV1-positive sensory nerves play a counter-regulatory role against salt-induced increases in blood pressure [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] . The underlying mechanism of anti-hypertensive effects of TRPV1 may involve its counter-balancing role against the activation of the renin-angiotensin-aldosterone system [7][8][9] , sympathetic nervous system [10] , endothelin system [11,12] , superoxide generation system [13,14] , and epithelial sodium transporters [15] .…”

Functional Antagonism between Endogenous Neuropeptide Y and Calcitonin Gene-Related Peptide in Mesenteric Resistance Arteries

“…A role for endogenous CGRP herein has not been considered yet. Renal CGRP-containing sensory-motor nerves markedly affect renal function, and they reduce blood pressure increases in response to increased salt intake (Wang et al, 1998;Huang and Wang, 2001). Modulation of these effects by NPY has not been investigated.…”

The vanilloid receptor and hypertension1

“…We next studied aldosterone and its interaction with the sensory nervous system in the induction of salt-sensitive hypertension, in light of the aforementioned finding that PRA is insufficiently suppressed in neonatally capsaicin-pretreated rats challenged with a salt load [54,55] . Both vehicleand capsaicin-treated rats fed a high-salt diet was given spironolactone, an aldosterone receptor antagonist for 3 weeks.…”