Key result
Mycophenolate mofetil reduces urinary angiotensinogen augmentation by ~67% and mitigates hypertensive kidney injury in rats.
Why the study?
Macrophages and pro-inflammatory cytokines may mediate intrarenal angiotensinogen augmentation in hypertension, prompting investigation into the effects of immunosuppression with mycophenolate mofetil.
Does mycophenolate mofetil reduce intrarenal angiotensinogen augmentation in Angiotensin II-dependent hypertension in Sprague-Dawley rats?
Does mycophenolate mofetil reduce intrarenal angiotensinogen augmentation in Angiotensin II-dependent hypertension in Sprague-Dawley rats?
Answers are grounded in this paper and cite their sources.
Immunosuppression with mycophenolate mofetil mitigates intrarenal angiotensinogen augmentation and subsequent kidney injury in Angiotensin II-dependent hypertension, highlighting the role of macrophages and cytokines in this process.
Augmentation of intrarenal angiotensinogen (AGT) leads to further formation of intrarenal angiotensin II (Ang II) and the development of hypertensive kidney injury. Recent studies demonstrated that macrophages and the enhanced production of pro-inflammatory cytokines can be crucial mediators of renal AGT augmentation in hypertension. Accordingly, this study investigated the effects of immunosuppression by mycophenolate mofetil (MMF) on intrarenal AGT augmentation. Ang II (80 ng/min) was infused with or without daily administration of MMF (50 mg/kg) to Sprague-Dawley rats for 2 weeks. Mean arterial pressure (MAP) in Ang II infused rats was slightly higher (169.7 ± 6.1 mmHg) than the Ang II + MMF group (154.7 ± 2.0 mmHg), but was not statistically different from the Ang II + MMF group. MMF treatment suppressed Ang II-induced renal macrophages and IL-6 elevation. Augmentation of urinary AGT by Ang II infusion was attenuated by MMF treatment (control: 89.3 ± 25.2, Ang II: 1194 ± 305.1, and Ang II + MMF: 389 ± 192.0 ng/day). The augmentation of urinary AGT by Ang II infusion was observed before the onset of proteinuria. Elevated intrarenal AGT mRNA and protein levels in Ang II infused rats were also normalized by the MMF treatment (AGT mRNA, Ang II: 2.5 ± 0.2 and Ang II + MMF: 1.5 ± 0.1, ratio to control). Ang II-induced proteinuria, mesangial expansion and renal tubulointerstitial fibrosis were attenuated by MMF. Furthermore, MMF treatment attenuated the augmentation of intrarenal NLRP3 mRNA, a component of inflammasome. These results indicate that stimulated cytokine production in macrophages contributes to intrarenal AGT augmentation in Ang II-dependent hypertension, which leads to the development of kidney injury.
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Satou et al. (2022) studied Angiotensin II-Dependent Hypertension. Mycophenolate mofetil (MMF) vs. Ang II alone was evaluated on Urinary angiotensinogen (AGT) augmentation (ng/day). Mycophenolate mofetil attenuated Angiotensin II-induced urinary angiotensinogen augmentation (389 ± 192.0 vs 1194 ± 305.1 ng/day) and mitigated hypertensive kidney injury in rats.
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