Immunological evidence that kidney is primary source of circulating inactive prorenin in rats

Kim, S.; Hosoi, Masayuki; Nakajima, Kiyomi; Yamamoto, Kenjiro

doi:10.1152/ajpendo.1991.260.4.e526

Cited by 13 publications

(17 citation statements)

References 20 publications

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“…[2][3][4] CD prorenin may then be released to cause pathological actions at the (pro)renin receptor or may be cleaved to serve as a source of renin in the face of JGA renin suppression. Our work supports other studies assigning the kidneys as the primary source of prorenin in the rat species, 25 but work in humans suggests that there are also significant, nonrenal sources of prorenin. 26 (Pro)renin in the CD may enter the tubular lumen ( Figure 1B) to access local RAS in the distal nephron, 5 culminating in intratubular Ang II generation.…”

Section: Discussionsupporting

confidence: 90%

The Collecting Duct Is the Major Source of Prorenin in Diabetes

et al. 2008

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Abstract-In addition to the juxtaglomerular apparatus, renin is also synthesized in renal tubular epithelium, including the collecting duct (CD). Angiotensin (Ang) II differentially regulates the synthesis of juxtaglomerular (inhibition) and CD (stimulation) renin. Because diabetes mellitus, a disease with high intrarenal renin-Ang system and Ang II activity, is characterized by high prorenin levels, we hypothesized that the CD is the major source of prorenin in diabetes. Renin granular content was visualized using in vivo multiphoton microscopy of the kidney in diabetic Munich-Wistar rats. Diabetes caused a 3.5-fold increase in CD renin, in contrast to less pronounced juxtaglomerular changes. Ang II type 1 receptor blockade with Olmesartan reduced CD renin to control levels but significantly increased juxtaglomerular renin. Using a fluorogenic renin assay, the prorenin component of CD renin content was measured by assessing the difference in enzymatic activity of medullary homogenates before and after trypsin activation of prorenin. Trypsinization caused no change in control renin activity but a 5-fold increase in diabetes. Studies on a CD cell line (M1) showed a 22-fold increase in renin activity after trypsinization and a further 35-fold increase with Ang II treatment. Therefore, prorenin significantly contributes to baseline CD renin. Diabetes, possibly via Ang II, greatly stimulates CD prorenin and causes hyperplasia of renin-producing connecting segments. These novel findings suggest that, in a rat model of diabetes, prorenin content and release from the CD may be more important than the juxtaglomerular apparatus in contrast to the existing paradigm. (Hypertension. 2008;51:1597-1604.)

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Section: Discussionsupporting

confidence: 90%

The Collecting Duct Is the Major Source of Prorenin in Diabetes

et al. 2008

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“…To compare the inhibitory manner of the renin activity by anti-renin serum 31 between adrenal extract and plasma, the samples (100 fil) of adrenal extracts or plasma were incubated with serially diluted anti-renin serum or nonimmunized rabbit serum as control at 4°C for 24 hours, and the residual renin activity was measured as described above.…”

Section: Inhibition Of the Angiotensin I-generating Activity Of Adrenmentioning

confidence: 99%

“…31 - 32 In brief, the sample of plasma (200-300 /il) from nonnephrectomized and 24-hour-nephrectomized SHRSP and WKY rats was applied to a G3.000SW column (0.75x60 cm; Tosoh, Yamaguchi, Japan) equilibrated with 50 mM sodium phosphate (pH 7.4) containing 0.2 M NaCl and 5 mM EDTA. The elution was performed at a flow rate of 0.5 ml/min, and fractions were collected every 30 or 60 seconds.…”

Section: Measurement Of Plasma Proreninmentioning

confidence: 99%

“…The anti-Pro N IgG and anti-Pro C IgG used recognize the amino-terminal and the carboxyl-terminal portions of the prosegment of rat prorenin, respectively, as described. 31 The immunoprecipitation using protein A-Sepharose was carried out as described. 31 Percent inhibition of the enzymatic activity of inactive renin fraction after trypsin activation by anti-mature rat renin IgG was determined as described.…”

Section: Measurement Of Plasma Proreninmentioning

confidence: 99%

“…31 The immunoprecipitation using protein A-Sepharose was carried out as described. 31 Percent inhibition of the enzymatic activity of inactive renin fraction after trypsin activation by anti-mature rat renin IgG was determined as described. 31 …”

Section: Measurement Of Plasma Proreninmentioning

confidence: 99%

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Adrenal and circulating renin-angiotensin system in stroke-prone hypertensive rats.

et al. 1992

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The plasma and adrenal renin-angiotensin system in stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats were examined in animals at 5, 11, 18, and 25 weeks of age. Plasma active renin was significantly increased in 18-and 25-week-old SHRSP with impaired renal function, whereas there was no difference in the plasma prorenin level or renal renin content between the two strains at all ages examined. Thus, the rate of activation of prorenin seems to be enhanced in the kidney of SHRSP with malignant hypertension. Adrenal renin contents were severalfold higher in SHRSP than WKY rats at all ages. However, adrenal angiotensin peptides were not increased in SHRSP aged 5 and 11 weeks. In 18-week-old SHRSP, adrenal angiotensin II (Ang II) and HI (Ang III) levels were fourfold and 1.8-fold higher, respectively, than in WKY rats, accompanied by 1.5-fold higher plasma aldosterone. Increased adrenal angiotensin and plasma aldosterone were also found in 25-week-old SHRSP. Zonal distribution studies indicated that the elevated Ang H and DI in SHRSP were derived mainly from the capsular tissue (the zona glomerulosa). To examine the contribution of circulating angiotensin to the adrenal angiotensin content, effects of bilateral nephrectomy on adrenal angiotensin and renin were examined in 18-week-old rats. At 24 hours after nephrectomy, plasma angiotensin, prorenin, and active renin were decreased to almost negligible concentrations. Conversely, in both adrenal capsular and decapsular tissues of SHRSP and WKY rats, neither angiotensin nor renin was significantly decreased after nephrectomy. These results suggest that the increase in adrenal capsular Ang II contents in SHRSP may be partly due to an enhanced local production or Ang II. The renin-angiotensin system also participates in the pathophysiology of malignant hypertension in SHRSP, as shown by previous reports.24 -26 However, previous research done on the renin-angiotensin system of SHRSP has been limited to the circulating system.

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Tissue renin-angiotensin systems: new insights from experimental animal models in hypertension research

et al. 2001

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Renin was first isolated in the kidney by Tigerstedt and Bergman over 100 years ago. Almost 50 additional years were necessary to isolate the renin substrate angiotensinogen and to show its cleavage to angiotensin (Ang). Further studies were then needed to demonstrate that Ang I is converted via an angiotensin-converting enzyme to Ang II. The circulating renin-angiotensin system, with blood pressure regulatory and aldosterone stimulatory roles, served well for decades. However, more recent information on Ang II and its action in terms of cell proliferation, hypertrophy, and hyperplasia as well as immune-modulatory and even intracellular functions, have focused attention on local Ang II generation and effects. These investigations necessarily began in the kidney, but quickly moved to other organs including the brain, heart, adrenal gland, and vessel wall and formed the basis for the concept of independent tissue renin-angiotensin systems. Both renin and Ang II have even been implicated in intracellular activities. This review presents some selected aspects of the historical development of this concept and summarizes discoveries relying primarily on animal models which demonstrate that Ang II is generated locally and acts in tissues as a local peptidergic system. Comprehensiveness in such an endeavor is not possible. We focus largely on work from our own group, not because the work is necessarily worthy of such scrutiny but rather because of our own familiarity with the contents.

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Immunological evidence that kidney is primary source of circulating inactive prorenin in rats

Cited by 13 publications

References 20 publications

The Collecting Duct Is the Major Source of Prorenin in Diabetes

The Collecting Duct Is the Major Source of Prorenin in Diabetes

Adrenal and circulating renin-angiotensin system in stroke-prone hypertensive rats.

Tissue renin-angiotensin systems: new insights from experimental animal models in hypertension research

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