title: Effect of angiotensin II receptor antagonism on vascular hypertrophy and aortic impedance in abdominal aortic-banded rat.
abstract: Vascular hypertrophy is considered to be an adaptive response to increased arterial wall stress in hypertension. Although there are several reports concerning the effect of angiotensin II inhibition on the development of vascular hypertrophy, little information is available as to its effect on vascular hypertrophy in parallel with the evaluation of arterial wall characteristics. The goal of this study was to evaluate the effect of angiotensin II type 1 receptor antagonist TCV-116 on pressure overload-induced vascular hypertrophy in parallel with the assessment of aortic impedance. Low dose (LD; 0.3 mg/kg/day) or high dose (HD; 3.0 mg/kg/day) of TCV-116 was administered to abdominal aortic-banded rats over 4 weeks; then hemodynamics and morphology were evaluated. In both the LD and HD groups, blood pressures were decreased to a similar extent compared with those of the vehicle-treated group (P < .05). Left ventricular (LV) weight and LV weight/body weight ratio was inhibited in both TCV-116-treated groups (P < .05), whereas the media cross-sectional area of the aorta was inhibited only in the HD group (P < .05). After the treatment of TCV-116 (LD, HD), total systemic resistance was decreased compared with the vehicle-treated group (P < .05), but there was no significant difference between the TCV-116-treated groups. In contrast, the first harmonic of the impedance modulus revealed the decrease only in the HD group (P < .05). TCV-116 attenuated the development of pressure overload LV hypertrophy and vascular hypertrophy as well; however, the dose of TCV-116 required for the inhibition of vascular hypertrophy was significantly higher than that for LV hypertrophy. Vascular hypertrophy may be less pressure dependent than cardiac hypertrophy. On chronic addition of high dose of TCV-116, arterial wave reflection was decreased in association with the attenuation of vascular hypertrophy.
authors.affiliation: Second Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Obayashi
authors.forename: M
authors.initials: M
authors.lastname: Yano
authors.forename: M
authors.initials: M
authors.lastname: Kohno
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Ohkusa
authors.forename: M
authors.initials: M
authors.lastname: Konishi
authors.forename: M
authors.initials: M
authors.lastname: Matsuzaki
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001012:Aorta, Abdominal / Q000187:drug effects / Q000503:physiopathology* / Q000601:surgery*; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology*; D001835:Body Weight / Q000187:drug effects; D003250:Constriction; D004305:Dose-Response Relationship, Drug; D006984:Hypertrophy / Q000517:prevention & control; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000517:prevention & control; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles; D013997:Time Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C077793:candesartan cilexetil