A Possible Interaction Between Systemic and Renal Angiotensinogen in the Control of Blood Pressure

Ramkumar, Nirupama; Stuart, Deborah; Jin, Ying; Kohan, Donald E.

doi:10.1093/ajh/hps078

Cited by 13 publications

(7 citation statements)

References 22 publications

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“…29 Indeed this novel observation is consistent with the recent description of hepatocyte hypertrophy in a mouse model of ADPKD and PLD generated by the insertion of a human PKD1 mutation, and demonstration that polycystin 1 and polycystin 2 are expressed in hepatocytes where their reduced expression/function may cause the hepatocyte hypertrophy observed by Hopp et al 31 Interestingly, many cytokine and growth factors implicated in hepatic regeneration after liver mass reduction are upregulated in PLD. 3032-36 …”

Section: Discussionmentioning

confidence: 99%

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Liver Involvement in Early Autosomal-Dominant Polycystic Kidney Disease

Hogan¹,

Abebe²,

Torres³

et al. 2015

Clinical Gastroenterology and Hepatology

103

108

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Background & Aims Polycystic liver disease (PLD), the most common extra-renal manifestation of autosomal-dominant polycystic kidney disease (ADPKD), has become more prevalent due to increased life expectancy, improved renal survival, reduced cardiovascular mortality, and renal replacement therapy. No studies have fully characterized PLD in large cohorts. We investigated whether liver and cyst volumes associate with volume of the hepatic parenchyma, results from liver laboratory tests, and patient-reported outcomes. Methods We performed a cross-sectional analysis of baseline liver volumes, measured by magnetic resonance imaging, and their association with demographics, results from liver laboratory and other tests, and quality of life. The data were collected from a randomized, placebo-controlled trial underway at 7 tertiary-care medical centers to determine whether the combination of an angiotensin I converting enzyme inhibitor and angiotensin II receptor blocker was superior to the inhibitor alone, and whether low blood pressure (<110/75mmHg) was superior to standard blood pressure (120–130/70–80mmHg), in delaying renal cystic progression in 558 patients with ADPKD, stage 1–2 chronic kidney disease, and hypertension (15–49 years old). Results We found hepatomegaly to be common among patients with ADPKD. Cysts and parenchyma contributed to hepatomegaly. Cysts were more common and liver and cyst volumes were greater in women, increasing with age. Patients with advanced disease had relative loss of liver parenchyma. We observed small abnormalities in results from liver laboratory tests, and that splenomegaly and hypersplenism associated with the severity of PLD. Higher liver volumes were associated with lower quality of life. Conclusions Hepatomegaly is common even in early-stage ADPKD and not accounted for by cysts alone. Parenchymal volumes are larger, compared with liver volumes of patients without ADPKD or with those predicted by standardized equations—even among patients without cysts. The severity of PLD is associated with altered biochemical and hematologic features, as well as quality of life.

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Section: Discussionmentioning

confidence: 99%

“…Hormone overproduction at either site is associated with hypertension in mouse transgenic models, and there is some basis for this underlying mechanism in humans. 35, 36 …”

Section: Discussionmentioning

confidence: 99%

Liver Involvement in Early Autosomal-Dominant Polycystic Kidney Disease

Hogan¹,

Abebe²,

Torres³

et al. 2015

Clinical Gastroenterology and Hepatology

103

108

View full text Add to dashboard Cite

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“…In contrast, there were no differences in urine AGT excretion rate or plasma and kidney Ang-II levels between rats on a high salt diet versus normal salt diet without infusion of Ang-II. In preliminary studies, our group has compared mice with overexpression of mouse AGT in liver alone, proximal tubule alone, or in both organs [35]. Mice with overexpression of AGT in kidney alone or in both liver and kidney were comparably hypertensive on a normal Na diet, whereas liver AGT overexpression alone did not affect BP on a normal Na diet.…”

Section: Salt-sensitive Hypertension and Diabetesmentioning

confidence: 99%

Proximal tubule angiotensinogen modulation of arterial pressure

Ramkumar

Kohan

2013

Current Opinion in Nephrology and Hypertension

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Purpose of review Although the existence of a complete intrarenal renin–angiotensin system is now well established, its role in modulating tubule sodium transport and blood pressure is incompletely understood. Several recent studies have shed light on one component of the system, proximal tubule-derived angiotensinogen (AGT). This review discusses the synthesis, regulation and function of AGT in the proximal tubule. Recent findings Under normal sodium intake, AGT within the S1 and S2 segments of the proximal tubule may derive from the systemic circulation, whereas the S3 segment synthesizes AGT. Urinary AGT likely primarily reflects proximal tubule-derived AGT. Proximal tubule AGT synthesis is regulated by high Na intake, angiotensin-II and inflammatory cytokines. Transgenic expression of mouse AGT in the proximal tubule causes hypertension. Overexpression of rat AGT in the proximal tubule leads to hypertension, enhanced reactive oxygen species generation via NADPH oxidase, tubular apoptosis and tubulointerstitial fibrosis; these effects can be mitigated by catalase overexpression. Summary Proximal tubule-derived AGT has the potential to modulate blood pressure and sodium balance, and promote renal injury. Interactions with the systemic renin–angiotensin system may influence the role of proximal tubule-derived AGT in the kidney.

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“…23 Numerous rat studies reported a correlation between local RAS activity in the kidneys and the development of HT. [28][29][30] Blood pressure variability has emerged as a clinical index of potential pathophysiological relevance. Studies have shown that an increase in ambulatory blood pressure variability is associated with endothelial dysfunction, asymptomatic organ damage, clinical target organ damage, and development and progression of cardiovascular and renal diseases.…”

Section: Discussionmentioning

confidence: 99%

Relationship between blood pressure variability and renal activity of the renin–angiotensin system

et al. 2015

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Local renin-angiotensin system (RAS) activity in the kidneys is a pathogenetic factor in patients with primary hypertension. This study aimed to determine the relationship between local kidney RAS activity and blood pressure variability, as the literature currently lacks any such study. The study included 73 consecutive primary hypertensive patients. All patients underwent 24-h ambulatory blood pressure monitoring to determine the average real variability (ARV) index, as an indicator of blood pressure variability. Local RAS activity was determined using the urine angiotensinogen/creatinine (UAGT/UCre) ratio. The high UAGT/UCre ratio group had significantly higher mean 24-h systolic ARV than the low UAGT/UCre ratio group (13.2±3.4 vs 11.0±2.6, P=0.003). Similarly, the high UAGT/UCre ratio group had significantly higher mean 24-h diastolic ARV than the low UAGT/UCre ratio group (10.8±3.2 vs 8.7±2.2, P=0.001). Multivariate regression analysis showed that Log(UAGT/UCre) was an independent predictor of both 24-h diastolic ARV and 24-h systolic ARV. Local RAS activity in the kidneys might have a role in blood pressure variability. On the basis of these findings, we think that additional prospective studies are needed to more fully discern the effect of local RAS activity on blood pressure variability.

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A Possible Interaction Between Systemic and Renal Angiotensinogen in the Control of Blood Pressure

Cited by 13 publications

References 22 publications

Liver Involvement in Early Autosomal-Dominant Polycystic Kidney Disease

Liver Involvement in Early Autosomal-Dominant Polycystic Kidney Disease

Proximal tubule angiotensinogen modulation of arterial pressure

Relationship between blood pressure variability and renal activity of the renin–angiotensin system

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