title: Angiotensin II-induced cardiomyocyte hypertrophy and cardiac fibrosis in stroke-prone spontaneously hypertensive rats.
abstract: Angiotensin-converting enzyme inhibitors (ACEIs) cause regression of hypertensive left ventricular hypertrophy (LVH) by reducing angiotensin II, increasing bradykinin, or both. The mechanisms of these cardioprotective effects remain controversial. The aims of this study were to determine whether the cardioprotective effects of ACEIs are mediated by reducing angiotensin II and whether ACEIs ameliorate the morphologic, physiologic, and biochemical changes in the hearts of stroke-prone spontaneously hypertensive rats (SHRSPs). Male SHRSPs were treated with hydralazine, captopril, or candesartan, an angiotensin II type 1 receptor (AT1R) antagonist, from age 12 to 24 weeks. We measured systolic blood pressure (SBP), left ventricular weight (LVW), left ventricular (LV) myocyte cross-sectional area (myocyte size), LV Interstitial collagen volume fraction (ICVF), perivascular collagen area/luminal area ratio (PVCA/LA), the medial area to luminal area ratio (MA/LA), the relative amount of V3 myosin heavy chain (MHCV3), and coronary reserve maximum (coronary flow max/ventricular weight (CFmax/VW)). These parameters were compared with those of untreated SHRSPs and Wistar-Kyoto rats (WKYs). SHRSPs exhibited decreased coronary reserve and LVH with an increase in myocyte size, PVCA/LA, MA/LA, and MHCV3 at 12 weeks of age. In addition to these changes, 24-week-old SHRSPs showed an increase in ICVF. The LVW, coronary reserve, myocyte size, PVCA/LA, ICVF, and MHCV3 of SHRSPs treated with captopril or candesartan all approached control values. In contrast, hydralazine decreased only ICVF. These results suggest that ACEIs regress LVH and normalize coronary reserve by modulating the effects of angiotensin II via AT1R on the induction of cardiomyocyte hypertrophy, perivascular fibrosis, and medial thickening of intramyocardial coronary arteries in SHRSPs. We concluded that these effects, in addition to the reduction of SBP, are important in causing the regression of LVH.
authors.affiliation: Department of Internal Medicine, Yamanashi Medical University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Takano
authors.forename: H
authors.initials: H
authors.lastname: Kimura
authors.forename: J E
authors.initials: JE
authors.lastname: Obata
authors.forename: S
authors.initials: S
authors.lastname: Takeda
authors.forename: A
authors.initials: A
authors.lastname: Hata
authors.forename: K
authors.initials: K
authors.lastname: Shido
authors.forename: S
authors.initials: S
authors.lastname: Mochizuki
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshida
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D005355:Fibrosis; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000188:drug therapy* / Q000235:genetics; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D006830:Hydralazine; D003094:Collagen; D002216:Captopril; D018995:Myosin Heavy Chains; C081643:candesartan