Renal sympathetic nerve activity modulates afferent renal nerve activity by PGE₂-dependent activation of α₁- and α₂-adrenoceptors on renal sensory nerve fibers

Abstract

Kopp UC, Cicha MZ, Smith LA, Mulder J, Hö kfelt T. Renal sympathetic nerve activity modulates afferent renal nerve activity by PGE 2-dependent activation of ␣1-and ␣2-adrenoceptors on renal sensory nerve fibers. Am J Physiol Regul Integr Comp Physiol 293: R1561-R1572, 2007. First published August 15, 2007; doi:10.1152/ajpregu.00485.2007.-Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA). To test whether the ERSNA-induced increases in ARNA involved norepinephrine activating ␣-adrenoceptors on the renal sensory nerves, we examined the effects of renal pelvic administration of the ␣ 1-and ␣2-adrenoceptor antagonists prazosin and rauwolscine on the ARNA responses to reflex increases in ERSNA (placing the rat's tail in 49°C water) and renal pelvic perfusion with norepinephrine in anesthetized rats. Hot tail increased ERSNA and ARNA, 6,930 Ϯ 900 and 4,870 Ϯ 670% ⅐ s (area under the curve ARNA vs. time). Renal pelvic perfusion with norepinephrine increased ARNA 1,870 Ϯ 210% ⅐ s. Immunohistochemical studies showed that the sympathetic and sensory nerves were closely related in the pelvic wall. Renal pelvic perfusion with prazosin blocked and rauwolscine enhanced the ARNA responses to reflex increases in ERSNA and norepinephrine. Studies in a denervated renal pelvic wall preparation showed that norepinephrine increased substance P release, from 8 Ϯ 1 to 16 Ϯ 1 pg/min, and PGE 2 release, from 77 Ϯ 11 to 161 Ϯ 23 pg/min, suggesting a role for PGE 2 in the norepinephrineinduced activation of renal sensory nerves. Prazosin and indomethacin reduced and rauwolscine enhanced the norepinephrine-induced increases in substance P and PGE 2. PGE2 enhanced the norepinephrine-induced activation of renal sensory nerves by stimulation of EP4 receptors. Interaction between ERSNA and ARNA is modulated by norepinephrine, which increases and decreases the activation of the renal sensory nerves by stimulating ␣ 1-and ␣2-adrenoceptors, respectively, on the renal pelvic sensory nerve fibers. Norepinephrine-induced activation of the sensory nerves is dependent on renal pelvic synthesis/release of PGE 2. substance P; EP4 receptor; pelvis; prazosin; rauwolscine THERE IS CONSIDERABLE EVIDENCE for increased sympathetic nerve activation to further stimulate sensory nerve fibers following tissue injury (15). Studies on efferent renal sympathetic nerve activity (ERSNA) and afferent renal nerve activity (ARNA) suggest that such an interaction is not restricted to conditions of tissue injury but is an important mechanism regulating ERSNA during physiological conditions (30). The kidney has a rich supply of sympathetic nerves, which innervate all parts of the vasculature and the nephron (2). In contrast, the majority of the sensory nerve fibers are localized to the renal pelvic wall (25,26,32). There is anatomical support for an interaction between ERSNA and ARNA, as shown by the close relationship between unmyelinated sympathetic nerve fibers and myelinated afferent nerve fibers in renal tissue...

Soluble fms-Like Tyrosine Kinase-1 and Endothelial Adhesion Molecules (Intercellular Cell Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1) as Predictive Markers for Blood Pressure Reduction After Renal Sympathetic Denervation

“…The persistence of hypertensive blood pressure (BP) in patients with resistant hypertension is partially regulated by the renal sympathetic nerve system. [17][18][19][20][21] Renal sympathetic denervation (RSD) is an interventional treatment option for patients who have resistant hypertension, despite optimal medical treatment. 22,23 However, RSD is not effective in ≈8% to 12% of treated patients.…”

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

“…1 Not only do increases in ARNA decrease ERSNA but also reflex increases in ERSNA increase ARNA. 2,3 The increased ARNA will, in turn, decrease ERSNA via activation of the renorenal reflexes, a negative-feedback mechanism, to maintain low-level ERSNA.Changes in ERSNA modulate ARNA by the release of norepinephrine (NE), which activates ␣ 1 -adrenoceptors (ARs) and ␣ 2 -ARs on renal sensory nerves, leading to increases and decreases in ARNA, respectively. 2 The physiologic importance of the ERSNA-induced increases in ARNA is underlined by the interaction being modulated by dietary sodium.…”

“…1 The kidney also has abundant afferent sensory innervation, located primarily in the renal pelvic wall. 2,3 Sympathetic efferent nerve fibers and afferent sensory nerve fibers often run separately but intertwined in the same nerve bundles in the renal pelvic wall, 2 providing anatomic support for a functional interaction between efferent renal sympathetic nerve activity (ERSNA) and afferent renal nerve activity (ARNA). In normotensive rats, activation of the renal sensory nerves leads to decreases in ERSNA and natriuresis, an inhibitory renorenal reflex response.…”

Increased bilateral expression of α1-adrenoceptors on peripheral nerves, blood vessels and keratinocytes does not account for pain or neuroinflammatory changes after distal tibia fracture in rats

“…37 We recently reported that noradrenaline, released 38 from sympathetic vasomotor neurons or produced 39 locally in the epidermis, may augment inflammation after 40 distal tibia fracture by activating keratinocytes or 41 vascular endothelial cells (Li et al, 2013). In particular, (Hong and Abbott, 1996;Ali 54 et al, 1999;Nam et al, 2000;Hord et al, 2001;Xie 55 et al, 2001;Kim et al, 2005;Dogrul et al, 2006;Maruo 56 et al, 2006;Kopp et al, 2007;Meisner et al, 2007;57 Trevisani et al, 2007;Gibbs et al, 2008;Dawson et al, 58 2011;Donello et al, 2011). Notably, we recently reported 59 that a 1 -AR expression increased in dermal nerve bundles 60 4-28 days after partial sciatic nerve lesion (Drummond 61 et al, 2014b), and on nociceptive nerve fibers and kerati-62 nocytes 7 days after chronic constriction injury of the sci-63 atic nerve (Drummond et al, 2014a).…”