Impact of neurally mediated antidiuretic effect relative to pressure diuresis during acute changes in sympathetic nerve activity.

We examined urine excretion during primary acute sympathetic activation (PASA) in anesthetized Wistar-Kyoto rats. Since arterial pressure (AP) changes with sympathetic nerve activity (SNA) during PASA, urine excretion reflects a neurally mediated antidiuretic effect combined with an effect of pressure diuresis. We hypothesized that preventing AP changes under PASA would enable the direct estimation of the neurally mediated antidiuretic effect alone. We changed the isolated carotid sinus pressure stepwise from 60 to 180 mmHg and compared the relationship of normalized urine flow (nUF, urine flow normalized by body weight) versus SNA between conditions allowing and preventing baroreflex-mediated changes in the mean AP. The slope of the SNA-nUF relationship was [Formula: see text]nUFvar = 0.444 ± 0.074 µL·min-1·kg-1·%-1 when the mean AP was variable, whereas it was [Formula: see text]nUFfix = -0.143 ± 0.032 µL·min-1·kg-1·%-1 when the mean AP was fixed at 100 mmHg (n = 7 rats). The slope associated with the effect of pressure diuresis alone, calculated as [Formula: see text]nUFvar - [Formula: see text]nUFfix, was 0.586 ± 0.105 µL·min-1·kg-1·%-1. Hence, the potency of the neurally mediated antidiuretic effect |[Formula: see text]nUFfix|/([Formula: see text]nUFvar - [Formula: see text]nUFfix) was 0.235 ± 0.014 relative to the effect of pressure diuresis under PASA. Our findings would aid an integrative understanding of the effects of renal hemodynamic and sympathetic modulations on urine output function.

Angiotensin II inhibition increases diuresis during acute sympathetic activation in intact and denervated kidneys in rats with chronic myocardial infarction.

We examined urine excretion during primary acute sympathetic activation (PASA) in Wistar-Kyoto rats with myocardial infarction (MI). The rats underwent unilateral renal denervation (RDN) 7 weeks after coronary artery ligation. 4-10 days later, an acute experiment was performed under anesthetized conditions (n = 8 rats). Isolated carotid sinus pressure was changed stepwise from 60 to 180 mmHg, and the relationship between the arterial pressure (AP) and the normalized urine flow (nUF, urine flow normalized by the body weight) was examined. After obtaining the control data, an angiotensin II type 1 receptor blocker telmisartan (2.5 mg/kg) was intravenously administered. The effects of RDN, telmisartan, and heart weight (biventricular weight) on the relationship between AP and nUF were examined using multiple regression analyses. Regarding the slope of nUF versus AP (nUFslope), the constant term of the regression was positive (0.315 ± 0.069 µL·min-1·kg-1·mmHg-1), indicating that nUF increased with AP. The heart weight had a negative effect on nUFslope (P < 0.05), suggesting that the severity of MI was associated with the impairment of urine excretion. Telmisartan increased nUFslope by 0.358 ± 0.080 µL·min-1·kg-1·mmHg-1 (P < 0.001), whereas RDN had no significant effect on this parameter. The results indicate that unilateral RDN was unable to abolish the effect of the renin-angiotensin system on urine excretion during PASA. Circulating or locally produced angiotensin II, rather than ongoing renal sympathetic nerve activity, played a dominant role in the impairment of urine excretion during PASA in rats with chronic MI.

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

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.

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

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.