Hypertrophic growth of cultured neonatal rat heart cells mediated by type 1 angiotensin II receptor.
Primary cultures of neonatal cardiac myocytes were used to determine the identity of second messengers that are involved in angiotensin II (ANG II) receptor-mediated effects on cardiac hypertrophy and the type of ANG II receptor that is involved in ANG II-induced cell growth. Treatment of myocytes with ANG II significantly increased the protein-to-DNA and the RNA-to-DNA ratios. ANG II accelerated rates of protein synthesis by 24.9%. Intracellular free calcium was transiently increased after ANG II exposure. The activity of protein kinase C in particulate fractions was transiently increased after exposure to ANG II but returned to control level. The activity of protein kinase C in the cytosol was significantly decreased at all times after exposure to ANG II. After ANG II treatment, the content of c-Fos mRNA was increased. The stimulatory effects of ANG II on these parameters were inhibited by the type 1 angiotensin II receptor (AT1) antagonist, losartan. These studies demonstrate that ANG II-induced hypertrophic growth is, at least in part, mediated through AT1 receptors.
Miyata
S
S
First Department of Internal Medicine, Asahikawa Medical College, Hokkaido, Japan.
Haneda
T
T
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D001713:Biphenyl Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000473:pathology*; D002478:Cells, Cultured; D007093:Imidazoles / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D019808:Losartan; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009994:Osmolar Concentration; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D011493:Protein Kinase C; D019808:Losartan; D002118:Calcium