Aspects of molecular biology and biochemistry of the cardiac renin-angiotensin system.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Lindpaintner
K
K
German Institute for High Blood Pressure Research, University of Heidelberg.
Jin
M
M
Wilhelm
M
M
Toth
M
M
Ganten
D
D
D000818:Animals; D006321:Heart / Q000502:physiology*; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D012084:Renin-Angiotensin System