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

Kopp UC, Cicha MZ, Smith LA, Ruohonen S, Scheinin M, Fritz N, Hkfelt T. Dietary sodium modulates the interaction between efferent and afferent renal nerve activity by altering activation of alpha(2)-adrenoceptors on renal sensory nerves. Am J Physiol Regul Integr Comp Physiol 300: R298-R310, 2011. First published November 24, 2010; doi: 10.1152/ajpregu.00469.2010.-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 alpha(1)-and alpha(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 alpha(2)-AR in modulating the responsiveness of renal sensory nerves during low- and high-sodium diets. Immunohistochemical analysis suggested the presence of alpha(2A)-AR and alpha(2C)-AR subtypes on renal sensory nerves. During the low- sodium diet, renal pelvic administration of the alpha(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 alpha(2)-AR contributes to the reduced interaction between ERSNA and ARNA during low- sodium intake, whereas no/minimal activation of alpha(2)-AR contributes to the enhanced ERSNA-ARNA interaction under conditions of high sodium intake.