The Relationship between the Intrarenal Dopamine System and Intrarenal Renin-angiotensin System Depending on the Renal Function

Angiotensin-converting enzyme (ACE) 2, a newly emerging component of the renin-angiotensin system, is presumed to be a counterregulator against ACE in generating and degrading angiotensin II. It remains to be elucidated how mRNA levels of these two genes are quantitatively regulated in the kidney and also what kind of clinicopathological characteristics could influence the gene expressions in humans. Seventy-eight cases of biopsy-proven renal conditions were examined in detail. Total RNA from a small part of each renal cortical biopsy specimen was reverse transcribed, and the resultant cDNA was amplified for ACE, ACE2, and glyceraldehyde-3-phosphate dehydrogenase with a real-time PCR system. Then we investigated the relationship between clinicopathological variables and mRNA levels adjusted for glyceraldehyde-3-phosphate dehydrogenase. Statistically significant correlation was not observed between any clinicopathological variables and either of the gene expressions by pairwise comparison. However, a strong correlation was observed between the gene expressions of ACE and those of ACE2. Moreover, the ACE to ACE2 ratio was significantly higher in subjects with hypertension (HT) than that in subjects without HT. Whereas parameters of renal function, e.g. urinary protein excretion (UPE) and creatinine clearance (Ccr), are not significantly related to the ACE to ACE2 ratio as a whole, the HT status may reflect disease-induced deterioration of renal function. That is, UPE and Ccr of subjects with HT are significantly different from those without HT, in which a significant correlation is also observed between UPE and Ccr. Finally, stepwise regression analysis further revealed that only the HT status is an independent confounding determinant of the ACE to ACE2 ratio among the variables tested. Our data suggest that ACE2 might play an important role in maintaining a balanced status of local renin-angiotensin system synergistically with ACE by counterregulatory effects confounded by the presence of hypertension. Thus, ACE2 may exert pivotal effects on cardiovascular and renal conditions.

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1788 THE RELATIONSHIP BETWEEN RENIN-ANGIOTENSIN SYSTEM BLOCKADE AND TUMOR RECURRENCE IN NON-MUSCLE INVASIVE BLADDER CANCER

The Journal of Urology ◽

10.1016/j.juro.2013.02.2878 ◽

2013 ◽

Vol 189 (4S) ◽

Author(s):

Kazuyuki Yuge ◽

Akira Miyajima ◽

Nobuyuki Tanaka ◽

Suguru Shirotake ◽

Takeo Kosaka ◽

...

Keyword(s):

Bladder Cancer ◽

Tumor Recurrence ◽

Renin Angiotensin System ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Angiotensin System ◽

Renin Angiotensin ◽

Muscle Invasive ◽

The Relationship

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The relationship of the renin-angiotensin system in type I diabetes to microvascular disease.

Hypertension ◽

10.1161/01.hyp.7.6_pt_2.ii84 ◽

1985 ◽

Vol 7 (6_pt_2) ◽

Cited By ~ 5

Author(s):

P L Drury ◽

H J Bodansky

Keyword(s):

Type I Diabetes ◽

Microvascular Disease ◽

Renin Angiotensin System ◽

Type I ◽

Angiotensin System ◽

Renin Angiotensin ◽

Relationship Of ◽

The Relationship

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Intrarenal renin-angiotensin system in hypertensive patients with localized kidney cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17069 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17069-e17069

Author(s):

Roman Osokin ◽

Ekaterina Komarova ◽

Igor Aboyan ◽

Aleksey Yu. Maksimov ◽

Roman Ischenko ◽

...

Keyword(s):

Blood Pressure ◽

Arterial Hypertension ◽

Kidney Cancer ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Hypertensive Patients ◽

Renin Angiotensin ◽

Peritumoral Tissue ◽

The Relationship ◽

Angiotensin Converting Enzymes

e17069 Background: In the last decade, the relationship between arterial hypertension and the risk of developing kidney cancer has been pointed out. Some studies have shown that the metabolic imbalance of the components of the renal renin-angiotensin system (RAS) is associated with the development and progression of kidney cancer. Aim: To study the state of RAS in tumor and peritumoral tissues in hypertensive patients with kidney cancer. Methods: In patients with localized kidney cancer T1N0M0 and grade I-II arterial hypertension without special treatment (n = 40; KC + AH) in the samples of tumor (TT), peritumoral (PTT) and histologically unchanged tissue (HUT), the levels of angiotensin 1 and 2, 1-7 (AT1 and AT2, AT (1-7)) of angiotensin-converting enzymes (ACE and ACE2) were determined by ELISA. The comparison group consisted of patients with RC without impaired blood pressure (n = 55, KC). Results: In patients with KC, the level of AT1 is 1.5 times higher (p < 0.05), and AT2 is 1.6 times higher (p < 0.05) in TT against the background of unchanged content in PTT compared with HUT. The level of ACE is higher than HUT by 2.7 times, ACE2 - by 1.6 times (in all cases p < 0.05), and in PTT it is identical in HUT. In patients with KC + AH, the level of AT1 and AT2 in the TT is 1.8 times higher (p < 0.05) and 2.1 times (p < 0.01), respectively, the content of AT(1-7) is 1.6 times (p < 0.01). In PTT, AT1 is 1.6 times higher (p < 0.01) and AT2 is 1.9 times higher (p < 0.05), significantly lower than only AT2 in the TT (1.2 times at p < 0, 05). The level of AT(1-7) in the PTT is identical to the values in the GNT. The content of ACE and ACE2 in TT is 3.6 and 2.9 times higher, respectively, and in PTT is identical to that in TT. Correlation analysis revealed a reliable direct relationship in the studied groups for all parameters, while in the PTT of hypertensive patients, the relationship between the average blood pressure and the RAS peptide content had a higher tightness. Conclusions: An increase in the levels of angiotensin 1 and 2, angiotensin-converting enzymes ACE and ACE2 in the tumor tissues and peritumoral tissue in patients with localized kidney cancer, regardless of the presence of arterial hypertension at initially higher values in hypertensive patients, was shown. The presence of arterial hypertension in patients with KC changes the metabolism of local RAS in peritumoral tissue and is associated with an increase in the correlation between changes in the components of RAS and arterial hypertension.

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