Renoprotective effect of the addition of losartan to ongoing treatment with an angiotensin converting enzyme inhibitor in type-2 diabetic patients with nephropathy.

Angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are frequently used for the treatment for glomerulonephritis and diabetic nephropathy because of their albuminuria- or proteinuria-reducing effects. To many patients who are nonresponsive to monotherapy with these agents, combination therapy appears to be a good treatment option. In the present study, we examined the effects of the addition of an ARB (losartan) followed by titration upon addition and at 3 and 6 months (n=14) and the addition of an ACE-I followed by titration upon addition and at 3 and 6 months (n=20) to the drug regimen treatment protocol in type 2 diabetic patients with nephropathy for whom more than 3-month administration of an ACE-I or the combination of an ACE-I plus a conventional antihypertensive was ineffective to achieve a blood pressure (BP) of 130/80 mmHg and to reduce urinary albumin to <30 mg/day. During the 12-month treatment, addition of losartan or addition of an ACE-I to the treatment protocol reduced systolic blood pressure (SBP) by 10% and 12%, diastolic blood pressure (DBP) by 7% and 4%, and urinary albumin excretion by 38% and 20% of the baseline value, respectively. However, the effects on both BP and urinary albumin were not significantly different between the two therapies. In conclusion, addition of losartan or an ACE-I to an ongoing treatment with an ACE-I, or addition of an ACE-I to ongoing treatment with a conventional antihypertensive were equally effective at reducing the urinary albumin excretion and BP, and provided renal protection in patients with type-2 diabetic nephropathy.

Reduction of QTc dispersion by the angiotensin II receptor blocker valsartan may be related to its anti-oxidative stress effect in patients with essential hypertension.

QT dispersion has been reported to increase in patients with essential hypertension, and abnormal QT dispersion is associated with arrythmias and sudden cardiac death. However, whether change in QT dispersion is related to oxidative stress is unclear. We examined the effect of the angiotensin II receptor blocker valsartan on QT dispersion and the relationship between oxidative stress and QT dispersion in patients with essential hypertension. Hypertensive patients whose systolic blood pressure (SBP) was more than 140 mmHg and/or diastolic blood pressure (DBP) was more than 90 mmHg were treated with valsartan. Blood pressure was measured once a month for 6 months. The difference between the maximal and minimal QT intervals within a 12-lead surface ECG was measured and QT dispersion and QTc dispersion corrected by heart rate were obtained before and 6 months after treatment. Left ventricular mass (LVM) assessed by echocardiography was obtained at baseline and 6 months after treatment. Venous blood samples were obtained at baseline and 6 months after treatment to measure serum levels of lipoperoxidation (LPO) and type I and III procollagen. Treatment with valsartan significantly decreased SBP and DBP. QTc dispersion decreased significantly 6 months after treatment with valsartan as compared to the baseline values. Valsartan treatment did not affect the LVM. Valsartan significantly decreased the abnormally high LPO levels. The changes in QTc dispersion were positively correlated with changes in the serum levels of LPO and with changes in DBP. The correlation between changes in LPO and QTc dispersion was more close than that between changes in DBP and QTc dispersion. In conclusion, antihypertensive therapy with valsartan reduces QTc dispersion and this may be related to the ability of valsartan to reduce oxidative stress in patients with essential hypertension.