Effects of angiotensin II type-1 receptor blocker losartan on age-related cardiovascular risk in spontaneously hypertensive rats.
Ageing and hypertension are the major risk factors for the development of cardiovascular and renal diseases, and the renin-angiotensin system has been shown responsible for these pathologies. Thus, the aim of this study was to compare the effects of losartan, angiotensin II type-1 receptor blocker, on systolic (SBP), diastolic (DBP), and mean (MBP) blood pressure, pulse pressure (PP) and heart rate as well as regional haemodynamics, cardiac hypertrophy and biochemical parameters in adult (L(9): 9-month-old) and aged (L(18): 18-month-old) spontaneously hypertensive rats (SHRs). Aged match untreated SHRs served as controls (U(9): 9-month-old and U(18): 18-month-old). Aortal blood flow and resistance were significantly improved by losartan treatment in L(9) vs. U(9) (p < 0.05). In aged SHRs, losartan significantly reduced SBP, MBP, PP, right ventricle weight index, and improved age-related impairment of left ventricular weight index (U(18): 4.21 +/- 0.09 mg/g vs. U(9): 3.54 +/- 0.34 mg/g, p < 0.05 and vs. L(18): 3.65 +/- 0.07 mg/g, p < 0.001), carotid, renal, and aortal vascular resistance, and glomerular filtration rate (U(18): 2.75 +/- 0.27 ml/min/kg vs. U(9): 4.84 +/- 0.85 ml/min/kg, p < 0.05 and vs. L(18): 3.65 +/- 0.07 ml/min/kg, p < 0.05). These results demonstrate significantly impaired systemic and regional haemodynamics and left ventricular hypertrophy in old SHRs. Losartan decreased age and hypertension associated cardiovascular risk by decreasing vascular resistance and pressure overload, ventricular hypertrophy, and preserving kidney function.
Mihailović-Stanojević
Nevena
N
Department of Cardiovascular Physiology, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, P.O.Box 102, 11129 Belgrade, Serbia. nevena@imi.bg.ac.rs
Miloradović
Zoran
Z
Grujić-Milanović
Jelica
J
Ivanov
Milan
M
Jovović
Djurdjica
D
D000375:Aging; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000150:complications*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D012306:Risk
D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D019808:Losartan