Beneficial effect of myocardial angiogenesis on cardiac remodeling process by amlodipine and MCI-154.
The present study examined the effect of long-term treatment with amlodipine and MCI-154 (a Ca2+ sensitizer) on progressive cardiac dysfunction and microvasculature in the dilated cardiomyopathic (DCM) hamster heart. After treatment of DCM hamsters (Bio 53.58) with amlodipine or MCI-154 for 15 wk from the age of 5 wk, amlodipine and MCI-154 were found to cause an increase in left ventricular percent fractional shortening and decreases in left ventricular diastolic dimension and isovolumic relaxation time in echocardiograms (P < 0.01). A hemodynamic study showed that the diastolic time constant decreased in the amlodipine-treatment group (P < 0.05). In a morphometric study employing a double-staining method that discriminated arteriolar and venular capillaries, amlodipine and MCI-154 caused increases in total capillary density (P < 0.05) and the proportion of venular capillaries (P < 0.05). Moreover, Northern blot analysis showed that the expression of mRNA for vascular endothelial growth factor was significantly increased by amlodipine and MCI-154. They preserve coronary microvasculature in the DCM hamster and might induce angiogenesis of small vessels, thereby contributing to preservation of cardiac systolic and diastolic function.
Kumamoto
H
H
Department of Cardiovascular Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, Japan. hkumamo@med.hokudai.ac.jp
Okamoto
H
H
Watanabe
M
M
Onozuka
H
H
Yoneya
K
K
Nakagawa
I
I
Chiba
S
S
Watanabe
S
S
Mikami
T
T
Abe
K
K
Kitabatake
A
A
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D002311:Cardiomyopathy, Dilated / Q000473:pathology / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000502:physiology*; D006224:Cricetinae; D004452:Echocardiography; D016228:Endothelial Growth Factors / Q000235:genetics; D008222:Lymphokines / Q000235:genetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011724:Pyridazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000502:physiology*
D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011724:Pyridazines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D017311:Amlodipine; C052228:MCI 154