Open-loop analysis on sympathetically mediated arterial pressure and urine output responses in rats: effect of renal denervation

Abstract

Primary acute sympathetic activation (PASA) can increase arterial pressure (AP). Under this situation, the kidneys may receive mutually opposing influences from sympathetic activation: a direct anti-diuretic effect via the renal innervation and pressure diuresis. We examined whether PASA would reduce urine output regardless of the AP elevation. We also examined the impact of renal denervation (RDN) on urine output during PASA. The experiment was performed on rats 3 to 9 days after unilateral RDN (n = 10). Under anesthesia, systemic sympathetic nerve activity (SNA) was varied over a wide range via the carotid sinus baroreflex. The slope of urine flow versus SNA was positive (0.252 ± 0.052 μL·min^-1·kg^-1· %^-1) on the intact side, and it was greater on the denervated side (0.331 ± 0.069 μL·min^-1·kg^-1· %^-1, P < 0.05). In conclusion, urine output change was an effect of elevated AP during PASA. Nevertheless, RDN was able to augment pressure diuresis during PASA.

Keywords: Arterial pressure; Equilibrium diagram; Open-loop analysis; Pressure diuresis; Sympathetic nerve activity.

Fig. 1

Schema of the arterial baroreflex system. The baroreflex system may be divided into neural arc and peripheral arc subsystems. The negative sign in the neural arc indicates signal inversion through the neural arc. Under a baroreflex closed-loop condition (a), a decrease in arterial pressure (AP) due to an exogenous perturbation (P_D) induces reflex activation of sympathetic nerve activity (SNA), which counteracts the effect of P_D. Under this condition, the AP reduction and the reflex sympathetic activation act synergistically to reduce urine output. However, changes in AP and SNA are not always reciprocal. When SNA increases via a central command, an AP elevation ensues. We refer to this latter situation as primary acute sympathetic activation (PASA). This situation may be mimicked under a baroreflex open-loop condition by imposing P_D on the isolated baroreceptor regions (b). During PASA, the kidneys may receive mutually opposing influences from the increased SNA (an anti-diuretic effect through renal innervation) and the increased AP (a diuretic effect through an increase in renal perfusion pressure). If urine output decreases during PASA, the urine output change can be interpreted as a cause for the AP elevation. Conversely, if urine output increases during PASA, the urine output change needs to be interpreted as an effect of the AP elevation

Fig. 2

a Schema of experimental settings. Carotid sinus pressure (CSP) was controlled via a servo-pump system. Urine output was assessed from the hydrostatic pressure of cumulated urine. PC, personal computer. b An example time series obtained from one rat. CSP was changed in a stepwise manner with a step duration of 90 s. Sympathetic nerve activity (SNA) and arterial pressure (AP) decreased in response to the CSP elevations. Gray and black lines in the SNA plot indicate 10-Hz resampled and 2-s moving average signals, respectively. Gray and black lines in the AP plot indicate 200-Hz resampled and 2-s moving average signals, respectively. Urine volume (UV) is displayed as a 10-Hz resampled signal. The UV was greater on the renal denervation (RDN) side than the intact (INT) side. The open circles indicate 10-s averaged values used for data analysis

Fig. 3

Group-averaged static characteristics of the total reflex arc (a), neural arc (b), and peripheral arc (c) of the carotid sinus baroreflex. CSP carotid sinus pressure, AP arterial pressure; SNA sympathetic nerve activity. d The baroreflex equilibrium diagram constructed from the fitted neural and peripheral arcs. Downward and leftward arrowheads indicate the operating-point AP and SNA, respectively. e The relationship of normalized urine flow (nUF) versus SNA in the intact (INT) and renal denervation (RDN) sides. f The relationship of nUF versus AP in the INT and RDN sides. The vertical dashed line indicates the operating-point AP (op-AP). The horizontal arrowheads indicate nUF at the operating-point AP. ^†P < 0.01 by Wilcoxon signed-rank test. Data are expressed as mean ± SE values (n = 10 rats)