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

Abstract

Primary acute sympathetic activation (PASA) causes a subsequent arterial pressure (AP) elevation. In this case, an antidiuretic effect via the renal innervation and pressure diuresis can act antagonistically on the kidneys. We examined the effect of PASA on urine output in spontaneously hypertensive rats (SHR) 4-7 days after unilateral renal denervation (RDN) (n = 9). The slope of the plot of urine flow versus AP was positive (0.120 ± 0.031 μL min^-1 kg^-1 mmHg^-1) on the intact side, but it was less than 1/3 of the slope observed previously in normotensive Wistar-Kyoto rats (WKY). RDN did not normalize the slope of urine flow versus AP (0.179 ± 0.025 μL min^-1 kg^-1 mmHg^-1, P = 0.098 versus the intact side). The urine flow at the operating point of the AP tended to be greater on the denervated than the intact side (29.0 ± 1.8 vs. 25.3 ± 1.9 μL min^-1 kg^-1, P = 0.055). The percent increase (17.2 ± 7.2%) was not different from that observed previously in WKY. Although high-resting sympathetic nerve activity is prerequisite for maintaining hypertension in SHR, the effect of sympathetic innervation on the urine output function was not greater than that in WKY.

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

Fig. 1

An example time-series obtained from one rat. The carotid sinus pressure (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 CSP when the CSP was above 140 mmHg. 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 compared with the intact (INT) side, and the difference increased as time elapsed

Fig. 2

a–c Group-averaged static characteristics of the total reflex arc, neural arc, and peripheral arc, respectively, 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 points of SNA and AP, 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 op-AP. The P value was determined by the Wilcoxon signed-rank test. Data are expressed as mean ± SE values (n = 9 rats)