Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of α₂-adrenoceptors on renal sensory nerves

Abstract

Activation of efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which then reflexively decreases ERSNA via activation of the renorenal reflexes to maintain low ERSNA. The ERSNA-ARNA interaction is mediated by norepinephrine (NE) that increases and decreases ARNA by activation of renal α(1)-and α(2)-adrenoceptors (AR), respectively. The ERSNA-induced increases in ARNA are suppressed during a low-sodium (2,470 ± 770% s) and enhanced during a high-sodium diet (5,670 ± 1,260% s). We examined the role of α(2)-AR in modulating the responsiveness of renal sensory nerves during low- and high-sodium diets. Immunohistochemical analysis suggested the presence of α(2A)-AR and α(2C)-AR subtypes on renal sensory nerves. During the low-sodium diet, renal pelvic administration of the α(2)-AR antagonist rauwolscine or the AT1 receptor antagonist losartan alone failed to alter the ARNA responses to reflex increases in ERSNA. Likewise, renal pelvic release of substance P produced by 250 pM NE (from 8.0 ± 1.3 to 8.5 ± 1.6 pg/min) was not affected by rauwolscine or losartan alone. However, rauwolscine+losartan enhanced the ARNA responses to reflex increases in ERSNA (4,680 ± 1,240%·s), and renal pelvic release of substance P by 250 pM NE, from 8.3 ± 0.6 to 14.2 ± 0.8 pg/min. During a high-sodium diet, rauwolscine had no effect on the ARNA response to reflex increases in ERSNA or renal pelvic release of substance P produced by NE. Losartan was not examined because of low endogenous ANG II levels in renal pelvic tissue during a high-sodium diet. Increased activation of α(2)-AR contributes to the reduced interaction between ERSNA and ARNA during low-sodium intake, whereas no/minimal activation of α(2)-AR contributes to the enhanced ERSNA-ARNA interaction under conditions of high sodium intake.

Impaired Interaction Between Efferent and Afferent Renal Nerve Activity in SHR Involves Increased Activation of α 2 -Adrenoceptors

“…[23][24][25] In summary, our findings suggest that the interaction between ERSNA and ARNA is impaired in SHR due to increased activation of ␣ 2 -ARs and AT1 receptors in renal pelvic tissue. The studies in the isolated renal pelvic wall preparation, together with our immunohistochemical studies, 22 suggest that the suppressed ERSNA-ARNA interaction involves postsynaptic ␣ 2 -AR, located on or close to the renal sensory nerves.…”

“…2 Modulation of renal pelvic ␣ 2 -ARs contributes to the altered ERSNA-ARNA interaction during various dietary sodium intakes. 22 Activation of renal pelvic ␣ 2 -ARs is increased and decreased in low-and high-sodium diet rats, respectively. Whereas suppressed interaction between ERSNA and ARNA is a physiologically appropriate response in low-sodium dietary conditions to minimize sodium loss, an impaired ERSNA-ARNA interaction in SHR would contribute to the increased ERSNA and sodium retention, characteristics of hypertension.…”

“…21 Our immunohistochemical studies localized ␣ 2A -ARs and ␣ 2C -ARs on or close to the sensory nerves in the renal pelvic wall. 22 The suppressed responsiveness of the renal sensory nerves in rats fed a low-sodium diet involves increased activation of renal pelvic ␣ 2 -ARs. 22 Likewise in SHR, the high concentration of NE (6250 pmol/L) required to increase PGE 2 release in the current studies suggests that the ␣ 1 -AR-mediated increase in PGE 2 release is suppressed by a powerful NE-mediated activation of ␣ 2 -ARs.…”

“…22 The suppressed responsiveness of the renal sensory nerves in rats fed a low-sodium diet involves increased activation of renal pelvic ␣ 2 -ARs. 22 Likewise in SHR, the high concentration of NE (6250 pmol/L) required to increase PGE 2 release in the current studies suggests that the ␣ 1 -AR-mediated increase in PGE 2 release is suppressed by a powerful NE-mediated activation of ␣ 2 -ARs. These findings, together with the increased density of ␣ 2 -ARs in renal tissue in SHR, 11 suggested a role for increased activation of renal pelvic ␣ 2 -ARs in the impaired responsiveness of the renal sensory nerves in SHR.…”

“…Previous studies would suggest that ␣ 2 -AR-and AT1 receptormediated coupling to pertussis toxin-sensitive G i -proteins contributes to the impaired responsiveness of the renal sensory nerves to increases in ERSNA by suppressing PGE 2 -mediated activation of AC. 9,10,22 Although not studied in SHR, the increased PGE 2 release in the presence of rauwolscine may be related to cross-talk among the secondmessenger systems activated by G q , G i , and/or G s proteincoupled receptors. Activation of G i -coupled receptors has been shown to affect phospholipase C and/or PKC activity, either directly or via inhibition of the AC/cAMP transduction pathway in neuronal and nonneuronal cells.…”