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Substrate-dependent angiotensin II formation in the peripheral circulation.

M Ideishi1, M Sasaguri, M Ikeda

  • 1Department of Internal Medicine, Fukuoka University School of Medicine, Japan.

Life Sciences
|January 1, 1990
PubMed
Summary

Researchers discovered a new pathway for forming angiotensin II, separate from the known vascular renin-angiotensin system. This alternative system in rats is not affected by certain drugs but is sensitive to chymostatin, suggesting a novel regulatory mechanism.

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Area of Science:

  • Biochemistry
  • Physiology
  • Pharmacology

Background:

  • The vascular renin-angiotensin system (RAS) is crucial for regulating blood pressure and fluid balance.
  • Existing research primarily focuses on the well-established vascular RAS pathway.

Purpose of the Study:

  • To investigate the existence and characteristics of an alternative angiotensin II-forming system.
  • To differentiate this novel pathway from the conventional vascular RAS.

Main Methods:

  • Utilized a rat hindlimb perfusion system with synthetic substrates.
  • Assessed the sensitivity of angiotensin II formation to inhibitors like captopril, aprotinin, and chymostatin.
  • Compared angiotensin II generation from different substrates under varying conditions.

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Main Results:

  • Demonstrated an alternative angiotensin II-forming system independent of the vascular RAS.
  • This pathway exhibited resistance to captopril and aprotinin but high sensitivity to chymostatin.
  • Angiotensin II formation was substrate-dependent, with significantly higher generation from a tridecapeptide human renin substrate compared to angiotensin I in the presence of captopril.

Conclusions:

  • An alternative pathway for angiotensin II generation exists in peripheral circulation.
  • This novel system possesses distinct enzymatic properties compared to the vascular RAS.
  • Both pathways likely contribute to the regulation of peripheral circulation.