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Renal medullary (pro)renin receptor contributes to angiotensin II-induced hypertension in rats via activation of the local renin-angiotensin system.

Wang F, Lu X, Liu M, Feng Y, Zhou SF, Yang T - BMC Med (2015)

Bottom Line: (Pro)renin receptor (PRR) is a new component of the renin-angiotensin system and regulates renin activity in vitro.Further analysis of kidney injury, inflammation, biochemical indices and protein localization were performed in vivo or in vitro.In cultured rat vascular smooth muscle cells, angiotensin II induced parallel increases in soluble PRR and renin activity, and the latter was significantly reduced by PRO20.

View Article: PubMed Central - PubMed

Affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, #74 Zhongshan 2nd Road, Science and Technology Building, 6th Floor, Guangzhou, 510080, P. R. China.

ABSTRACT

Background: (Pro)renin receptor (PRR) is a new component of the renin-angiotensin system and regulates renin activity in vitro. Within the kidney, PRR is highly expressed in the renal medulla where its expression is induced by angiotensin II infusion. The objective of the present study was to test a potential role of renal medullary PRR during angiotensin II-induced hypertension.

Methods: A rat AngII infusion model (100 ng/kg/min) combined with renal intramedullary infusion of PRO20, a specific inhibitor of PRR, was builded. And the intravenous PRO20 infusion serve as control. Mean arterial pressure was recorded by radiotelemetry for one week. Further analysis of kidney injury, inflammation, biochemical indices and protein localization were performed in vivo or in vitro.

Results: Radiotelemetry demonstrated that AngII infusion elevated the mean arteria pressure from 108 ± 5.8 to 164.7 ± 6.2 mmHg. Mean arterial pressure decreased to 128.6 ± 5.8 mmHg (P < 0.05) after intramedullary infusion of PRO20, but was only modestly affected by intravenous PRO20 infusion. Indices of kidney injury, including proteinuria, glomerulosclerosis, and interstitial fibrosis, inflammation, and increased renal medullary and urinary renin activity following angiotensin II infusion were all remarkably attenuated by intramedullary PRO20 infusion. Following one week of angiotensin II infusion, increased PRR immunoreactivity was found in vascular smooth muscle cells. In cultured rat vascular smooth muscle cells, angiotensin II induced parallel increases in soluble PRR and renin activity, and the latter was significantly reduced by PRO20.

Conclusion: Renal medullary PRR mediates angiotensin II-induced hypertension, likely by amplifying the local renin response.

No MeSH data available.


Related in: MedlinePlus

Effect of intramedullary (pro)renin receptor (PRR) inhibition on renal inner medullary prorenin/renin expression in angiotensin II (AngII)-infused rats. The expression of prorenin/renin in the inner medulla was determined by using enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) determined in Control (CTR), AngII, or AngII + intramedullary PRO20-infused (AngII + IM RPO20) rats. a ELISA detection of prorenin/renin content. b qRT-PCR detection of renin mRNA expression. N = 5–6 per group. Data are means ± standard error
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Fig5: Effect of intramedullary (pro)renin receptor (PRR) inhibition on renal inner medullary prorenin/renin expression in angiotensin II (AngII)-infused rats. The expression of prorenin/renin in the inner medulla was determined by using enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) determined in Control (CTR), AngII, or AngII + intramedullary PRO20-infused (AngII + IM RPO20) rats. a ELISA detection of prorenin/renin content. b qRT-PCR detection of renin mRNA expression. N = 5–6 per group. Data are means ± standard error

Mentions: AngII infusion induces a local renin response in the renal medulla but suppresses systemic renin activity [16, 18, 27–29]. We hypothesized that PRR may be required to enhance the renal medullary renin response to AngII. As expected, following AngII infusion, renin activity was suppressed in plasma and the renal cortex but enhanced in the inner medulla and urine, and the latter response was blunted by IM PRO20 (Fig. 4a–d). ELISA showed that prorenin/renin content in the inner medulla was elevated by AngII infusion but was unaffected by IM PRO20 (Fig. 5a) and the same result was obtained by qRT-PCR of renin mRNA (Fig.5b), supporting the concept that PRR primarily regulates local renin activity but not renin expression. Of note, the ELISA kit was unable to differentiate between prorenin and renin.Fig. 4


Renal medullary (pro)renin receptor contributes to angiotensin II-induced hypertension in rats via activation of the local renin-angiotensin system.

Wang F, Lu X, Liu M, Feng Y, Zhou SF, Yang T - BMC Med (2015)

Effect of intramedullary (pro)renin receptor (PRR) inhibition on renal inner medullary prorenin/renin expression in angiotensin II (AngII)-infused rats. The expression of prorenin/renin in the inner medulla was determined by using enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) determined in Control (CTR), AngII, or AngII + intramedullary PRO20-infused (AngII + IM RPO20) rats. a ELISA detection of prorenin/renin content. b qRT-PCR detection of renin mRNA expression. N = 5–6 per group. Data are means ± standard error
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4641338&req=5

Fig5: Effect of intramedullary (pro)renin receptor (PRR) inhibition on renal inner medullary prorenin/renin expression in angiotensin II (AngII)-infused rats. The expression of prorenin/renin in the inner medulla was determined by using enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) determined in Control (CTR), AngII, or AngII + intramedullary PRO20-infused (AngII + IM RPO20) rats. a ELISA detection of prorenin/renin content. b qRT-PCR detection of renin mRNA expression. N = 5–6 per group. Data are means ± standard error
Mentions: AngII infusion induces a local renin response in the renal medulla but suppresses systemic renin activity [16, 18, 27–29]. We hypothesized that PRR may be required to enhance the renal medullary renin response to AngII. As expected, following AngII infusion, renin activity was suppressed in plasma and the renal cortex but enhanced in the inner medulla and urine, and the latter response was blunted by IM PRO20 (Fig. 4a–d). ELISA showed that prorenin/renin content in the inner medulla was elevated by AngII infusion but was unaffected by IM PRO20 (Fig. 5a) and the same result was obtained by qRT-PCR of renin mRNA (Fig.5b), supporting the concept that PRR primarily regulates local renin activity but not renin expression. Of note, the ELISA kit was unable to differentiate between prorenin and renin.Fig. 4

Bottom Line: (Pro)renin receptor (PRR) is a new component of the renin-angiotensin system and regulates renin activity in vitro.Further analysis of kidney injury, inflammation, biochemical indices and protein localization were performed in vivo or in vitro.In cultured rat vascular smooth muscle cells, angiotensin II induced parallel increases in soluble PRR and renin activity, and the latter was significantly reduced by PRO20.

View Article: PubMed Central - PubMed

Affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, #74 Zhongshan 2nd Road, Science and Technology Building, 6th Floor, Guangzhou, 510080, P. R. China.

ABSTRACT

Background: (Pro)renin receptor (PRR) is a new component of the renin-angiotensin system and regulates renin activity in vitro. Within the kidney, PRR is highly expressed in the renal medulla where its expression is induced by angiotensin II infusion. The objective of the present study was to test a potential role of renal medullary PRR during angiotensin II-induced hypertension.

Methods: A rat AngII infusion model (100 ng/kg/min) combined with renal intramedullary infusion of PRO20, a specific inhibitor of PRR, was builded. And the intravenous PRO20 infusion serve as control. Mean arterial pressure was recorded by radiotelemetry for one week. Further analysis of kidney injury, inflammation, biochemical indices and protein localization were performed in vivo or in vitro.

Results: Radiotelemetry demonstrated that AngII infusion elevated the mean arteria pressure from 108 ± 5.8 to 164.7 ± 6.2 mmHg. Mean arterial pressure decreased to 128.6 ± 5.8 mmHg (P < 0.05) after intramedullary infusion of PRO20, but was only modestly affected by intravenous PRO20 infusion. Indices of kidney injury, including proteinuria, glomerulosclerosis, and interstitial fibrosis, inflammation, and increased renal medullary and urinary renin activity following angiotensin II infusion were all remarkably attenuated by intramedullary PRO20 infusion. Following one week of angiotensin II infusion, increased PRR immunoreactivity was found in vascular smooth muscle cells. In cultured rat vascular smooth muscle cells, angiotensin II induced parallel increases in soluble PRR and renin activity, and the latter was significantly reduced by PRO20.

Conclusion: Renal medullary PRR mediates angiotensin II-induced hypertension, likely by amplifying the local renin response.

No MeSH data available.


Related in: MedlinePlus