Dietary sodium modulates the interaction between efferent renal sympathetic nerve activity and afferent renal nerve activity: role of endothelin

Abstract

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which in turn decreases ERSNA via activation of the renorenal reflexes in the overall goal of maintaining low ERSNA. We now examined whether the ERSNA-induced increases in ARNA are modulated by dietary sodium and the role of endothelin (ET). The ARNA response to reflex increases in ERSNA was enhanced in high (HNa)- vs. low-sodium (LNa) diet rats, 7,560 +/- 1,470 vs. 900 +/- 390%.s. The norepinephrine (NE) concentration required to increase PGE(2) and substance P release from isolated renal pelvises was 10 pM in HNa and 6,250 pM in LNa diet rats. In HNa diet pelvises 10 pM NE increased PGE(2) release from 67 +/- 6 to 150 +/- 13 pg/min and substance P release from 6.7 +/- 0.8 to 12.3 +/- 1.8 pg/min. In LNa diet pelvises 6,250 pM NE increased PGE(2) release from 64 +/- 5 to 129 +/- 22 pg/min and substance P release from 4.5 +/- 0.4 to 6.6 +/- 0.7 pg/min. In the renal pelvic wall, ETB-R are present on unmyelinated Schwann cells close to the afferent nerves and ETA-R on smooth muscle cells. ETA-receptor (R) protein expression in the renal pelvic wall is increased in LNa diet. In HNa diet, renal pelvic administration of the ETB-R antagonist BQ788 reduced ERSNA-induced increases in ARNA and NE-induced release of PGE(2) and substance P. In LNa diet, the ETA-R antagonist BQ123 enhanced ERSNA-induced increases in ARNA and NE-induced release of substance P without altering PGE(2) release. In conclusion, activation of ETB-R and ETA-R contributes to the enhanced and suppressed interaction between ERSNA and ARNA in conditions of HNa and LNa diet, respectively, suggesting a role for ET in the renal control of ERSNA that is dependent on dietary sodium.

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

“…Therefore, we hypothesized that the ERSNA-induced increases in ARNA would be impaired in SHR. Whereas a reduction of the ERSNA-ARNA interaction is an appropriate physiologic response to changes in dietary sodium in normal rats, 3 suppressed ERSNA-induced increases in ARNA in hypertensive rats would contribute to the increased arterial pressure by further increases in ERSNA and sodium retention.…”

“…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.…”

“…A high-sodium diet enhances and a lowsodium diet reduces the ERSNA-induced increases in ARNA. 3 The importance of the renorenal reflex-induced inhibition of ERSNA in the control of body fluid and sodium homeostasis was demonstrated in rats lacking intact afferent renal innervation. These rats are characterized by increased ERSNA, increased responsiveness of ERSNA to various sympathetic stimuli, and increased arterial pressure when fed a high-sodium diet.…”

“…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.…”

“…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.…”