Effects of Angiotensin II Type 1 Receptor Antagonist on Smooth Muscle Cell Phenotype in Intramyocardial Arteries from Spontaneously Hypertensive Rats

Abstract

To clarify the precise mechanisms involved in the reduced coronary flow reserve in hypertension, we com- is a vasoconstrictor and trophic factor that mediates contractile and proliferative actions in hypertension mainly by stimulating the Ang II type 1 (AT1) receptor (4, 5). Ang II is also important for vascular remodeling, since inhibition of the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors or AT1 receptor antagonists corrects vascular structure and endothelial dysfunction in small arteries, including endothelial dysfunction of the coronary vasculature, impairment of coronary hemodynamics, LV hypertrophy, and contractile dysfunction, thereby exacerbating myo-

Liver growth factor treatment restores cell-extracellular matrix balance in resistance arteries and improves left ventricular hypertrophy in SHR

“…ϩP Ͻ 0.05, SHR compared with WKY. SHR IMA structure, which is characterized by vessel narrowing, hypertrophy, perivascular fibrosis, and reduced vascularization (29,44). LGF treatment produced a significant reduction of the wall-to-lumen ratio, together with a normalization of the excessive perivascular collagen and the reduced VSMC number observed in SHR.…”

“…These alterations are not only important for the progression of hypertension but are also predictors of cardiovascular events in hypertensive subjects (48,55). Hypertension is also associated with left ventricular hypertrophy (LVH), characterized by an increase in myocite size or cell number, fibrosis, intramyocardial artery (IMA) remodeling, and reduction of the vascular component (29,44,59). These alterations contribute to an insufficient blood supply to the myocardium and favor the development of adverse cardiovascular events (31,37,43,46).…”

Nifedipine Activates PPARγ and Exerts Antioxidative Action Through Cu/ZnSOD Independent of Blood-pressure Lowering in SHRSP

“…In each heart, the wall-to-lumen ratio of 10 intramyocardial arteries 150 m in diameter, as well as the severity of perivascular fibrosis and collagen deposition in the heart, which was representative of collagen, including types and , were identified using birefringency under polarized light illumination. These parameters were then evaluated using a computer-assisted image analysis system with NIH Image 1.62 as previously reported 17) , and the mean values for each heart were used for statistical analysis.…”

“…DHE specifically reacts with intracellular ·O2 and is converted to the red fluorescent compound ethidium, which then binds irreversibly to double-stranded DNA and appears as punctuate nuclear staining. These data were evaluated in a blind fashion using a computer-assisted image analysis system with NIH Image 1.62 as previously reported 17) , and the mean value for each heart was used for statistical analysis and expressed as a percentage of the corresponding data for the WKY group. The specificity of DHE and DCF signals for ·O2 and H2O2 detection, respectively, was confirmed by preincubation with polyethylene glycol-superoxide dismutase (PEG-SOD; 500 U/mL, SIGMA) and PEG-catalase (350 U/mL, SIGMA), respectively 22,23) .…”

Different Effects of Amlodipine and Enalapril on the Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase-Extracellular Signal-Regulated Kinase Pathway for Induction of Vascular Smooth Muscle Cell Differentiation In Vivo

“…SMCs in the media express 2 isoforms of the smooth muscle (SM) myosin heavy chain (MHC; SM1 and SM2) and 2 types of nonmuscle MHC (NMHC) isoforms (NMHC-B/SMemb and NMHC-A) (1,2). We recently reported that angiotensin II receptor type 1-mediated NAD(P)H oxidase-generated reactive oxygen species, endothelial NO synthase (eNOS) and phosphoinositide 3-kinase (PI3-K)/protein kinase B (PKB) (Akt), as well as GATA-6, a zinc finger transcription factor that regulates SM-MHC isoforms in vascular SMCs, might be crucial determinants for the vascular SMC phenotype in hypertension in vivo (3,4). It has also been reported that the forced expression of active forms of mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) 1 and MAP kinase (MAPK) kinase (MKK) 6, which are the upstream kinases of ERK and p38 MAPK, respectively, induced de-differentiation of SMCs, indicating that the SMC phenotype would be determined by the balance between the strengths of the Akt pathway and the ERK and p38 MAPK pathways (5).…”