Diastolic wall stress and ANG II in cardiac hypertrophy and gene expression induced by volume overload.
We investigated the effects of diastolic wall stress (WS) and angiotensin II (ANG II) on the left ventricular (LV) hypertrophy (LVH) induced by volume overload and on the gene expression of LV adrenomedullin (AM) and atrial natriuretic peptide (ANP) in volume overload. Diastolic WS was pharmacologically manipulated with (candesartan) or without (calcium channel blocker manidipine) inhibition of ANG II type 1 receptors in aortocaval-shunted rats over 6 wk. Diastolic WS reached a plateau at 2 wk and subsequently declined regardless of further LVH. Although diastolic WS was decreased to a similar extent by both compounds, candesartan blunted LVH over 6 wk, whereas manidipine blunted LVH at 2 wk but not after 4 wk. Levels of AM and ANP gene expression increased as LVH developed but were completely suppressed by candesartan over 6 wk. ANP expression level was also attenuated by manidipine over 6 wk, whereas AM expression level was suppressed at 2 wk but not after 4 wk by manidipine. We concluded that diastolic WS and ANG II might be potent stimuli for the LVH and LV AM and ANP gene expression in volume overload and that diastolic WS could be relatively involved in the early LVH and in the gene expression of ANP rather than of AM.
Yamakawa
H
H
First Department of Internal Medicine, Miyazaki Medical College, Miyazaki 889-1692, Japan.
Imamura
T
T
Matsuo
T
T
Onitsuka
H
H
Tsumori
Y
Y
Kato
J
J
Kitamura
K
K
Koiwaya
Y
Y
Eto
T
T
D053607:Adrenomedullin; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure; D001810:Blood Volume; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003971:Diastole / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D009578:Nitrobenzenes; D010455:Peptides / Q000235:genetics*; D010879:Piperazines; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013314:Stress, Mechanical; D013777:Tetrazoles / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010455:Peptides; D010879:Piperazines; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D053607:Adrenomedullin; C054218:manidipine; D009320:Atrial Natriuretic Factor; C081643:candesartan