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. 1989;27(Suppl 2):159S–165S. doi: 10.1111/j.1365-2125.1989.tb03477.x

Aspects of molecular biology and biochemistry of the cardiac renin-angiotensin system

K Lindpaintner, M Jin, M Wilhelm, M Toth, D Ganten
PMCID: PMC1379743  PMID: 2669912

Abstract

1 Recent evidence for the existence of extrarenal tissue renin-angiotensin systems has raised the question of whether such a system also exists in the heart.

2 Evidence is presented for a cardiac renin-angiotensin system based on molecular biological and biochemical data. In addition, the question of whether the components of this system interact as a locally integrated, biologically functioning unit is addressed.

3 Using radio-labelled cRNA probes prepared from specific cDNA fragments, renin and angiotensin gene expression in atria and ventricles of the rat heart have been documented by Northern blot and liquid hybridization analysis. Relative signal strength for both mRNAs was highest in the atria, followed by the right and left ventricle.

4 Using specific, h.p.l.c.-controlled RIAs for angiotensin peptides, the presence of both angiotensin I and angiotensin II in all anatomical regions of the monkey and rat heart have been demonstrated; similarly, presence of converting enzyme activity was also ascertained by direct in vitro determinations.

5 Additional experiments evaluating the spontaneous release of angiotensin from rat isolated, perfused hearts revealed a bimodal pattern of high, but rapidly declining rates during the first hour (perhaps representing washout of a pool sequestrated from plasma), followed by a prolonged period of steady, low level release, consistent with the secretion of locally synthesized protein.

6 In separate experiments aimed at examining the possible local integration of the components of the cardiac renin-angiotensin system, angiotensin II concentrations were measured in the coronary sinus effluent of rat isolated, perfused hearts. Infusion of angiotensin I resulted in the prompt appearance of angiotensin II, amounting to a single pass fractional conversion of 6.42 ± 0.33%. Dose-dependent inhibition of this effect by simultaneous infusion of captopril further supports the existence of a specific intracardiac pathway for the activation of angiotensin II.

7 To establish the potential role of endogenous cardiac angiotensinogen as a substrate for locally formed angiotensin, rat isolated, perfused hearts were exposed to infusions of purified renin. Angiotensin I, undetectable prior to renin infusion, was dose-dependently released into the coronary circulation at peak rates ranging from 2.4 ± 0.7 fmol min-1 to 1.4 ± 0.2 pmol min-1, of which 7.2 ± 1.1% was intracardially converted to angiotension II. All renin effects were blocked in the presence of a specific pentapeptide renininhibitor.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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