Effects of AT1 receptor block begun late in life on normal cardiac aging in rats.
The goal of this study was to determine how short-term (12 weeks) angiotensin type I (AT1) block begun late in life affects aspects of myocardial biology and physiologic function altered by normal aging. Exercise capacity, myocardial morphology, histopathology, and coronary vascular function (degree of coronary vasodilation in response to adenosine) were evaluated in 53 Fischer 344 rats. Adult (6 months of age) and old (21 months of age) rats were studied after 12 weeks of either control drinking water, a low dose of candesartan that did not significantly lower blood pressure (1 mg/kg/d), or a high dose of candesartan (10 mg/kg/d). Significant age-associated changes in exercise capacity (38% decrease), coronary dilation in response to adenosine (41% decrease), and histopathology occurred but were not affected by candesartan treatment. Age-associated myocardial hypertrophy occurred as indicated by an increase in heart weight-to-tibia length ratio from 0.27 g/cm +/- 0.01 in the adult controls to 0.34 g/cm +/- 0.02 in the old controls (P < 0.05). This hypertrophy in the aged hearts was significantly attenuated by both low-dose (0.30 g/cm +/- 0.01) and high-dose (0.29 g/cm +/- 0.01) candesartan (P < 0.05). Echocardiographic measurements indicate that the candesartan-induced decrease in hypertrophy occurred concomitantly with slight decreases in septal wall thickness and left ventricular (LV) chamber diameter. It is concluded that short-term AT1 block, even when initiated late in life, can decrease age-associated LV hypertrophy independent of blood pressure-lowering effects.
D000241:Adenosine / Q000008:administration & dosage / Q000493:pharmacokinetics; D000375:Aging / Q000187:drug effects; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D017079:Exercise Tolerance / Q000187:drug effects; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects; D013777:Tetrazoles; D013977:Tibia / Q000033:anatomy & histology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000241:Adenosine; C077793:candesartan cilexetil