What question did this study set out to answer?

To elucidate the mechanisms underlying the differential regulation of plasma renin activity between angiotensin receptor blocker and angiotensin-converting enzyme inhibitor treatments in juxtaglomerular cells.

January 1, 2003Hypertension ResearchOpen Access

Angiotensin II Type 2 Receptor Inhibits Prorenin Processing in Juxtaglomerular Cells

Q: What is the clinical evidence from this study?

Study design: Other. Population: Renin-angiotensin system regulation. Intervention: Angiotensin II type 1 receptor blocker (CV11974) vs. Control buffer or Angiotensinogen alone. Primary outcome: Active renin content (ARC) (p=<0.05).

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Key result

Distinct from ACE inhibitors, angiotensin II type 1 receptor blockers inhibit prorenin processing in juxtaglomerular cells through angiotensin II type 2 receptors, decreasing active renin content.

Why the study?

Does an ARB inhibit prorenin processing in rat juxtaglomerular cells compared to an ACEI?

Population

Primary cultures of rat juxtaglomerular cells isolated from kidneys of male Sprague-Dawley rats, n=6 primary…

Comparison

Angiotensinogen 100 nmol/l with or without ACEI… vs Control buffer or Aogen alone.

Design

Preclinical

Follow-up

12 hours

Authors

AIAtsuhiro IchiharaGeneral / Preventive / Lipids MHMatsuhiko HayashiKawasaki Hospital NHNobuhisa HirotaKeio University

Discussion

Member takes

Implication

Does not support altering ARB or ACEI use in patients; leaves open translation of AT2-mediated prorenin effects to human hypertension.

Key Points

To elucidate the mechanisms underlying the differential regulation of plasma renin activity between angiotensin receptor blocker and angiotensin-converting enzyme inhibitor treatments in juxtaglomerular cells.
Treated primary cultures of rat juxtaglomerular (JG) cells (n=6) with angiotensinogen alone and in combination with an ACE inhibitor (delapril/CV3317) or an ARB (candesartan metabolite/CV11974).
Evaluated renin secretion rate (RSR), active renin content (ARC), and total renin content (TRC) following selective modulation with an angiotensin II type 2 receptor blocker (PD123319) and agonist (CGP42212A).
Angiotensinogen increased medium angiotensin II from 14 ± 2 to 440 ± 9 pg/ml and suppressed RSR from 39.6 ± 5.4% to 6.3 ± 1.8%, while delapril decreased angiotensin II to 58 ± 14 pg/ml and restored RSR to 39.8 ± 4.1% without altering ARC or TRC.
CV11974 elevated medium angiotensin II to 486 ± 15 pg/ml, increased RSR to 40.9 ± 9.8%, and decreased ARC from 63.2 ± 6.8 to 21.6 ± 3.6 ng Ang I·h⁻¹·10⁶ cells⁻¹ without affecting TRC; this reduction was abolished by PD123319.
The type 2 receptor agonist CGP42212A similarly reduced ARC from 60.8 ± 3.0 to 25.3 ± 2.8 ng Ang I·h⁻¹·10⁶ cells⁻¹ and increased RSR to 49.7 ± 4.7% without altering TRC, effects that were also prevented by PD123319.

Structured PICO

Does an ARB inhibit prorenin processing in rat juxtaglomerular cells compared to an ACEI?

Population

In vitro study using primary cultures of juxtaglomerular cells isolated from male Sprague-Dawley rats to evaluate the differential effects of ARBs and ACEIs on renin synthesis and secretion.

Intervention

Angiotensinogen (Aogen) 100 nmol/l with or without ACEI (delapril hydrochloride, 10 micromol/l), ARB (candesartan cilexetil active metabolite, 10 micromol/l), AT2 receptor blocker (PD123319, 10 micromol/l), or AT2 receptor agonist (CGP42212A, 0.1 micromol/l).

Comparator

Control buffer or Aogen alone.

Outcome

Renin secretion rate (RSR), active renin content (ARC), total renin content (TRC), and medium Ang II levels at 12 hours.surrogate

Main Result

Absolute Event Rate: 21.6% vs 63.2%

p-value: p=<0.05

ARBs, distinct from ACEIs, inhibit prorenin processing in juxtaglomerular cells via AT2 receptors, suggesting a mechanism for decreased plasma renin activity during long-term ARB therapy.

Limitations

In vitro study using rat cells, which may not fully reflect in vivo human physiology
No competing peptide against the AT2 receptor antibody was available for immunocytochemistry

Cite This Study

Ichihara et al. (2003) studied Renin-angiotensin system regulation. Angiotensin II type 1 receptor blocker (CV11974) vs. Control buffer or Angiotensinogen alone was evaluated on Active renin content (ARC) (p=<0.05). Distinct from ACE inhibitors, angiotensin II type 1 receptor blockers inhibit prorenin processing in juxtaglomerular cells through angiotensin II type 2 receptors, decreasing active renin content.

synapsesocial.com/papers/6a86d23d740e6cf4b5cf8249 https://doi.org/10.1291/hypres.26.915

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Angiotensin II Type 2 Receptor Inhibits Prorenin Processing in Juxtaglomerular Cells

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Limitations

Cite This Study

Angiotensin II Type 2 Receptor Inhibits Prorenin Processing in Juxtaglomerular Cells

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Also Consider