Upregulation of the brain renin–angiotensin system in rats with chronic renal failure

Nishimura, Masato; Takahashi, Hakuo; Yoshimura, Manabu

doi:10.1111/j.1748-1716.2006.01663.x

Cited by 17 publications

(14 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Expression of the intrarenal angiotensinogen and renin was suppressed and ACE expression was unchanged in Mdk +/+ mice, which was consistent with previous findings after 5/6 nephrectomy of rats (19,20) (Supplemental Figure 2, A-C). In contrast to the kidney, the lung showed significant increases in ACE expression and its activity 2 and 4 weeks after renal ablation (Figure 2, A-E).…”

Section: Figuresupporting

confidence: 81%

“…CKD has also been linked with damage in other organs, especially with cardiovascular damage (so-called cardiorenal syndrome) (30). It is particularly interesting that RAS components are increased in the heart and brain of subtotally nephrectomized rats (20,31) and that Ang II amounts are increased in the isolated perfused hind limbs of uremic rats (32). Inhibitors of the RAS, e.g., angiotensin receptor blockers and ACE inhibitors, are indeed the first choice of therapy for CKD (33).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The growth factor midkine regulates the renin-angiotensin system in mice

Hobo¹,

Yuzawa²,

Kosugi³

et al. 2009

J. Clin. Invest.

View full text Add to dashboard Cite

The renin-angiotensin system plays a pivotal role in regulating blood pressure and is involved in the pathogenesis of kidney disorders and other diseases. Here, we report that the growth factor midkine is what we believe to be a novel regulator of the renin-angiotensin system. The hypertension induced in mice by 5/6 nephrectomy was accompanied by renal damage and elevated plasma angiotensin II levels and was ameliorated by an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin receptor blocker. Notably, ACE activity in the lung, midkine expression in the lung, and midkine levels in the plasma were all increased after 5/6 nephrectomy. Exposure to midkine protein enhanced ACE expression in primary cultured human lung microvascular endothelial cells. Furthermore, hypertension was not induced and renal damage was less severe in midkine-deficient mice. Supplemental administration of midkine protein to midkine-deficient mice restored ACE expression in the lung and hypertension after 5/6 nephrectomy. Oxidative stress might be involved in midkine expression, since expression of NADH/NADPH oxidase-1, -2, and -4 was induced in the lung after 5/6 nephrectomy. Indeed, the antioxidative reagent tempol reduced midkine expression and plasma angiotensin II levels and consequently ameliorated hypertension. These results suggest that midkine regulates the renin-angiotensin system and mediates the kidney-lung interaction after 5/6 nephrectomy.

show abstract

Section: Figuresupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

The growth factor midkine regulates the renin-angiotensin system in mice

Hobo¹,

Yuzawa²,

Kosugi³

et al. 2009

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…39,43,44 Furthermore, the brain renin-angiotensin system was upregulated in rats with chronic renal failure. 45 Therefore, the renin-angiotensin system in the brain may stimulate the generation of central oxidative stress associated with renal dysfunction. Moreover, brain aldosterone and mineralocorticoid receptors, which are stimulated by the renin-angiotensin system, can also be involved in central oxidative stress-induced sympathoexcitation.…”

Section: Fujita Et Al Sympathoexcitation Via Brain Ros In Ckd 109mentioning

confidence: 99%

Sympathoexcitation by Brain Oxidative Stress Mediates Arterial Pressure Elevation in Salt-Induced Chronic Kidney Disease

et al. 2012

View full text Add to dashboard Cite

Abstract-Hypertension is very prevalent in chronic kidney disease and critical for its prognosis. Sympathoexcitation and oxidative stress have been demonstrated to be involved in chronic kidney disease. We have shown previously that sympathoexcitation by brain oxidative stress mediates arterial pressure elevation in the salt-sensitive hypertension model, Dahl salt-sensitive rats. Thus, we investigated whether sympathoexcitation by excessive brain oxidative stress could contribute to arterial pressure elevation in salt-induced chronic kidney disease model rats. Young (3-week-old) male Sprague-Dawley rats were randomly assigned to a uninephrectomy or sham operation and then subjected to either a normal salt (0.5%) or high-salt (8.0%) diet for 4 weeks. The young salt-loaded uninephrectomized rats exhibited sympathoexcitation, hypertension, and renal injury, proteinuria and global glomerulosclerosis together with tubulointerstitial damage. Under urethane anesthesia and artificial ventilation, renal sympathetic nerve activity, arterial pressure, and heart rate decreased to a greater degree in the salt-loaded uninephrectomized rats than in the nonsalt-loaded uninephrectomized rats and the salt-loaded or nonsalt-loaded sham-operated rats, when Tempol, a membrane-permeable superoxide dismutase mimetic, was infused acutely into the lateral cerebral ventricle. Oxidative stress in the hypothalamus, measured by lucigenin chemiluminescence, was also significantly greater. Furthermore, in the salt-loaded uninephrectomized rats, antioxidant treatment with chronic intracerebroventricular Tempol decreased sympathetic nerve activity and arterial pressure, which, in turn, led to a decrease in renal damage. Similar effects were elicited by treatment with oral moxonidine, the central sympatholytic agent.

show abstract

“…9 It has also been reported that ARNs are connected to the central areas, including the nucleus tractus solitarius, the paraventricular nucleus, the supraoptic nucleus, the subfornical organ and others. 26,27 In the present study, ICV injection of an Ang II AT1 receptor antagonist, CV-11974, significantly attenuated the increases in RSNA and blood pressure in response to elevation of pelvic pressure. Collectively, these findings support the hypothesis that afferent nervous information from the kidney is transmitted to the CNS and stimulates the systemic sympathetic activity via the CNS RAS-mediated pathways.…”

Section: Wky Rats Shrsmentioning

confidence: 91%

Roles of central renin-angiotensin system and afferent renal nerve in the control of systemic hemodynamics in rats

et al. 2011

View full text Add to dashboard Cite

Afferent renal nerves (ARNs) convey signals generated by physiological changes in the kidney to the central nervous system. The aim of this study was to determine whether ARNs contribute to cardiovascular regulation through central renin-angiotensin system (RAS)-dependent pathways. Blood pressure and renal sympathetic nerve activity (RSNA) were monitored during elevations in pelvic pressure in anesthetized Wistar-Kyoto Izm (WKY) rats and spontaneously hypertensive Izm rats (SHRs). In both groups of rats, blood pressure and RSNA were significantly increased in response to elevations in renal pelvic pressure in a pressure-dependent fashion, which were prevented by renal denervation. Injection of an angiotensin II type I receptor blocker (CV-11974, 10 lg) into the intracerebroventricular region significantly suppressed the vasopressor and sympathoexcitatory responses to the increases in pelvic pressure in both WKY rats and SHRs, although these inhibitory effects of CV-11974 in SHRs appeared to be weaker than in WKY rats. These results indicate that signals transmitted by ARNs have an important role in the control of systemic hemodynamics through regulating central RAS-mediated changes in sympathetic nerve activity.

show abstract

Upregulation of the brain renin–angiotensin system in rats with chronic renal failure

Abstract: The brain renin-angiotensin system in subtotally nephrectomized SHR appears to be activated via afferent nerves from the remnant kidney, resulting in sympathetic overactivity and hypertension in this chronic renal failure model.

Cited by 17 publications

References 27 publications

The growth factor midkine regulates the renin-angiotensin system in mice

The growth factor midkine regulates the renin-angiotensin system in mice

Sympathoexcitation by Brain Oxidative Stress Mediates Arterial Pressure Elevation in Salt-Induced Chronic Kidney Disease

Roles of central renin-angiotensin system and afferent renal nerve in the control of systemic hemodynamics in rats

Contact Info

Product

Resources

About