Renin-angiotensin system in stretch-induced hypertrophy of cultured neonatal rat heart cells.
Although it is well known that mechanical load to cardiac muscles causes cardiac hypertrophy, little is known about how mechanical load is transduced into the activation of intracellular signals which are linked to cell growth. We investigated whether the cardiac renin-angiotensin system was involved in stretch-induced hypertrophy of cultured neonatal rat heart myocytes. Myocytes were cultured with serum-free medium in a deformable silicon dish. Stretch of cardiac myocytes significantly increased the protein/DNA ratio at culture days 6 and 7, and the RNA/DNA ratio at culture days 4 and 5. Stretch significantly accelerated rates of protein synthesis by 15%. c-fos mRNA expression was significantly increased after stretch. The stimulatory effects of cell stretch on these parameters were significantly inhibited by the angiotensin converting enzyme inhibitor, captopril, or the type 1 angiotensin II receptor antagonist, losartan. The concentrations of angiotensin I and angiotensin II in culture media were significantly increased by stretch. Stretch did not change the angiotensin converting enzyme activity. These studies demonstrate that mechanical stretch activates the cardiac renin-angiotensin system in a autocrine and paracrine system which acts as an initial mediator of the stretch-induced hypertrophic growth.
Miyata
S
S
First Department of Internal Medicine, Asahikawa Medical College, Hokkaido, Japan.
Haneda
T
T
Osaki
J
J
Kikuchi
K
K
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000809:Angiotensins / Q000502:physiology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D002478:Cells, Cultured; D006321:Heart / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D009124:Muscle Proteins / Q000096:biosynthesis; D009470:Muscle Spindles / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D009124:Muscle Proteins; D013777:Tetrazoles; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D012083:Renin; D019808:Losartan