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 compared the effects of the angiotensin II type 1 (AT1) receptor antagonist FK-739 with those of the angiotensin-converting enzyme (ACE) inhibitor enalapril for 6 weeks on the smooth muscle (SM) cell phenotype in intramyocardial arteries from male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Compared with WKY, SHR showed a significant increase in left ventricular (LV) hypertrophy and fibrosis, blood pressure (BP), and vascular remodeling of the intramyocardial arteries, and a significant decrease in endothelial NO synthase and the contractile-type myosin heavy chain isoform SM2 of the intramyocardial arteries as well as calponin 1 and GATA-6. In the hearts of SHR, both drugs equivalently and significantly reduced BP, which was still significantly higher than that in the WKY groups, and also reduced LV hypertrophy and fibrosis, whereas endothelial NO synthase was significantly restored. Although both drugs showed little effect on the vascular remodeling of the intramyocardial arteries in the SHR hearts, FK-739, but not enalapril, significantly restored SM2 and GATA-6 in the SHR hearts to the same levels as those of the vehicle WKY group. The effects of the two drugs on these indices were not observed in the three WKY hearts. Thus, the AT1 receptor antagonist may modulate the SM cell phenotype toward the contractile-type more effectively than the ACE inhibitor before the morphological changes occur in the intramyocardial arteries of the SHR hearts.

• Authors: Makoto Kubo, Seiji Umemoto, Kozo Fujii, Shinichi Itoh, Masakazu Tanaka, Shinji Kawahara, Masunori Matsuzaki
• Journal: Hypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 27 Issue 9 Pg. 685-93 (Sep 2004) ISSN: 0916-9636 [Print] England
• PMID: 15750263 (Publication Type: Journal Article)

Chemical References

• 2-butyl-3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-3H-imidazo(4,5-b)pyridine
• Actins
• Angiotensin II Type 1 Receptor Blockers
• Angiotensin-Converting Enzyme Inhibitors
• Calcium-Binding Proteins
• DNA-Binding Proteins
• GATA6 Transcription Factor
• Imidazoles
• Microfilament Proteins
• Pyridines
• Transcription Factors
• calponin
• Enalapril
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type III
• Nos3 protein, rat
• Myosin Heavy Chains

Topics

• Actins (metabolism)
• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Body Weight
• Calcium-Binding Proteins (metabolism)
• Coronary Vessels (drug effects, physiology)
• DNA-Binding Proteins (metabolism)
• Enalapril (pharmacology)
• GATA6 Transcription Factor
• Heart Rate
• Hypertension (drug therapy, physiopathology)
• Imidazoles (pharmacology)
• Immunoblotting
• Male
• Microfilament Proteins
• Muscle, Smooth, Vascular (drug effects, metabolism)
• Myosin Heavy Chains (metabolism)
• Nitric Oxide Synthase (metabolism)
• Nitric Oxide Synthase Type III
• Pyridines (pharmacology)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Transcription Factors (metabolism)