Abstract
We investigate whether combined treatment with losartan, an angiotensin II receptor blocker, and exercise training (ET) in spontaneously hypertensive rats (SHR) would have an additive effect in reducing hypertension and improving baroreflex sensitivity when compared with losartan alone. Male SHR (8 weeks old) were assigned to 3 groups: sedentary placebo (SP, N = 16), sedentary under losartan treatment (SL, N = 11; 10 mg kg-1 day-1, by gavage), and ET under losartan treatment (TL, N = 10). ET was performed on a treadmill 5 days/week for 60 min at 50% of peak VO2, for 18 weeks. Blood pressure (BP) was measured with a catheter inserted into the carotid artery, and cardiac output with a microprobe placed around the ascending aorta. The baroreflex control of heart rate was assessed by administering increasing doses of phenylephrine and sodium nitroprusside (iv). Losartan significantly reduced mean BP (178 16 vs 132 12 mmHg) and left ventricular hypertrophy (2.9 0.4 vs 2.5 0.2 mg/g), and significantly increased baroreflex bradycardia and tachycardia sensitivity (1.0 0.3 vs 1.7 0.5 and 2.0 0.7 vs 3.2 1.7 bpm/mmHg, respectively) in SL compared with SP. However, losartan combined with ET had no additional effect on BP, baroreflex sensitivity or left ventricular hypertrophy when compared with losartan alone. In conclusion, losartan attenuates hypertension and improves baroreflex sensitivity in SHR. However, ET has no synergistic effect on BP in established hypertension when combined with losartan, at least at the dosage used in this investigation.
Highlights
Hypertension is a major population health problem and is a precursor of various forms of cardiovascular disease such as congestive heart failure [1,2] but is considered a modifiable risk factor for morbidity and mortality
We investigate whether combined treatment with losartan, an angiotensin II receptor blocker, and exercise training (ET) in spontaneously hypertensive rats (SHR) would have an additive effect in reducing hypertension and improving baroreflex sensitivity when compared with losartan alone
Since a reduction in resting arterial blood pressure is associated with a decrease in risk factors, several pharmacological and nonpharmacological therapies for hypertension management have been assessed in many studies [3,4,5,6]
Summary
Hypertension is a major population health problem and is a precursor of various forms of cardiovascular disease such as congestive heart failure [1,2] but is considered a modifiable risk factor for morbidity and mortality. One of the most used AT1 receptor blockers, limits the development of hypertension [9,10] and decreases blood pressure levels in spontaneously hypertensive rats (SHR) and in patients with essential hypertension [11,12,13,14], low-intensity ET attenuates hypertension but fails to reduce blood pressure to normotensive levels [15,16] Both losartan treatment and ET independently improve the impaired baroreflex sensitivity in SHR (1719) and lead to cardiac remodeling with reduction of left ventricular hypertrophy [7,12,13,20,21,22,23].
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Schedule a callMore From: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
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