Contribution of circulating renin to local synthesis of angiotensin peptides in the heart.
The activity of a local cardiac renin-angiotensin system (RAS) has long been suspected in the promotion of cardiac pathologies including hypertrophy, ischemia, and infarction. All of the components of the RAS cascade have been demonstrated to be synthesized within the heart with the possible exception of the first enzyme in the cascade, renin. In the current study, we provide direct evidence that circulating renin can contribute to cardiac-specific synthesis of angiotensin peptides. Furthermore, we demonstrate this effect is independent of blood pressure and that in animals of comparable blood pressure, elevated circulating renin significantly enhances cardiac fibrosis. These results may serve to explain some of the cardiac pathologies associated with the RAS.
Prescott
G
G
Laboratory of Molecular Biochemistry of Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada.
Silversides
D W
DW
Chiu
S M
SM
Reudelhuber
T L
TL
D000803:Angiotensin I / Q000096:biosynthesis* / Q000378:metabolism; D000804:Angiotensin II / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019808:Losartan / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D009928:Organ Specificity; D010452:Peptide Biosynthesis / Q000187:drug effects / Q000502:physiology*; D012083:Renin / Q000032:analysis / Q000097:blood* / Q000378:metabolism / Q000502:physiology*; D019076:Transgenes
D000959:Antihypertensive Agents; D000804:Angiotensin II; D000803:Angiotensin I; D012083:Renin; D019808:Losartan