Cardiac renin and angiotensins. Uptake from plasma versus in situ synthesis.
The existence of a cardiac renin-angiotensin system, independent of the circulating renin-angiotensin system, is still controversial. We compared the tissue levels of renin-angiotensin system components in the heart with the levels in blood plasma in healthy pigs and 30 hours after nephrectomy. Angiotensin I (Ang I)-generating activity of cardiac tissue was identified as renin by its inhibition with a specific active site-directed renin inhibitor. We took precautions to prevent the ex vivo generation and breakdown of cardiac angiotensins and made appropriate corrections for any losses of intact Ang I and II during extraction and assay. Tissue levels of renin (n = 11) and Ang I (n = 7) and II (n = 7) in the left and right atria were higher than in the corresponding ventricles (P < .05). Cardiac renin and Ang I levels (expressed per gram wet weight) were similar to the plasma levels, and Ang II in cardiac tissue was higher than in plasma (P < .05). The presence of these renin-angiotensin system components in cardiac tissue therefore cannot be accounted for by trapped plasma or simple diffusion from plasma into the interstitial fluid. Angiotensinogen levels (n = 11) in cardiac tissue were 10% to 25% of the levels in plasma, which is compatible with its diffusion from plasma into the interstitium. Like angiotensin-converting enzyme, renin was enriched in a purified cardiac membrane fraction prepared from left ventricular tissue, as compared with crude homogenate, and 12 +/- 3% (mean +/- SD, n = 6) of renin in crude homogenate was found in the cardiac membrane fraction and could be solubilized with 1% Triton X-100. Tissue levels of renin and Ang I and II in the atria and ventricles were directly correlated with plasma levels (P < .05), and in both tissue and plasma the levels were undetectably low after nephrectomy. We conclude that most if not all renin in cardiac tissue originates from the kidney. Results support the contentions that in the healthy heart, angiotensin production depends on plasma-derived renin and that plasma-derived angiotensinogen in the interstitial fluid is a potential source of cardiac angiotensins. Binding of renin to cardiac membranes may be part of a mechanism by which renin is taken up from plasma.
Department of Pharmacology, Cardiovasculair Onderzoeksinstituut Erasmus Universiteit Rotterdam, The Netherlands.
A H
AH
Danser
J P
JP
van Kats
P J
PJ
Admiraal
F H
FH
Derkx
J M
JM
Lamers
P D
PD
Verdouw
P R
PR
Saxena
M A
MA
Schalekamp
D000808:Angiotensinogen / Q000032:analysis; D000809:Angiotensins / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D004792:Enzyme Precursors / Q000032:analysis; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D012083:Renin / Q000032:analysis* / Q000378:metabolism; D013552:Swine
D000809:Angiotensins; D004792:Enzyme Precursors; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A; D012083:Renin