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About 10 years have passed, since the first angiotensin receptor antagonist (ARB), losartan became commercially available in Japan. Six brands of ARB are now available. The excellent effects of ARBs have been demonstrated in recent large-scaled clinical trials such as CASE-J study, Jikei Heart study, HIJ-CREATE study etc. In these studies it was demonstrated that ARBs have moderate antihypertensive effects and pleiotropic actions beyond blood pressure reduction and furthermore ARBs show few side effects compared to other antihypertensive drugs. According to these excellent characteristics of ARBs, ARBs occupied the most important position in the treatment of hypertension. It is supposed that the increasing usage of ARBs will prolong the life span of Japanese people much more in future.

Mild hypertension is defined as blood pressure level of 140-159 mmHg systolic and/or 90-99 mmHg diastolic. The patients with blood pressure level of mild hypertension occupy about 60% of total hypertensive patients in Japan, and most of them are free of subjective symptoms except elevated blood pressure. However, some of the patients with mild hypertension develop cardiovascular events, since thay have occasionally cardiovascular damages on this level of blood pressure and several risk factors of cardiovascular diseases such as diabetes mellitus and hyperlipidemia.

The essence of Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2000) was introduced. JSH 2004 is a revised edition of JSH 2000. In JSH 2004, the significance of lifestyle modification is also emphasized as the basic treatment of hypertension, in which salt intake per day is reduced to below 6g/day. In drug therapy, Ca channel blockers, AII receptor blockers, ACE inhibitors, diuretics, beta -blockers and alpha-blockers are recommended as the main anti-hypertensive drugs. To obtain target blood pressure, a combined therapy of those drugs is recommended. In the management of aged hypertensive patients over 65, target blood pressure is generally below 140/90mmHg, but in those over 75, transient target blood pressure is below 150/90 mmHg, if hypertension is moderate or severe.

Since the publication of the Japanese guidelines for the treatment of hypertension in 2000, a lot of large-scale clinical trials on the treatment of hypertension have been reported. Furthermore new guidelines for the treatment of hypertension, such as JNC-VII and ESH-ESC guidelines have been reported in 2003. On the consideration of results of these trials and new guidelines, treatment strategy on hypertensive cardiovascular damage was described in this manuscript. The initiation criteria of drug therapy, modifications of life-style, selection of antihypertensive drugs and target blood pressure are various in each guideline. However, strict control of blood pressure is the most important to protect cardiovascular damages, regardless differences in the treatment strategy in each guideline. In the drug therapy Ca channel blockers, inhibitors of the renin-angiotensin system and diuretics are mainly used as monotherapy or a combination therapy to obtain the target blood pressure.

This 1.5-year prospective study compared the effects of angiotensin II receptor blocker, candesartan(n = 21), and ACE inhibitor(ACEI, n = 23) on proteinuria and renal function in patients with moderate renal impairment due to chronic glomerulonephritis. Blood pressure reductions were comparable between both groups. Proteinuria was significantly reduced from 2.1 +/- 0.4 (mean +/- SE) to 0.6 +/- 0.2 g/day(p0.001) with candesartan, and the reduction was significantly larger than with ACEI(p0.01). Serum creatinine did not increase with candesartan or ACEI, suggesting the renoprotective effect. Serum potassium increased significantly with both drugs from 6 months. Plasma aldosterone concentrations(PAC) showed a stronger suppression with candesartan(150 pg/ml before treatment and 51 at 1.5 years) than with ACEI(104 pg/ml at 1.5 years). Plasma renin activity with candesartan(1.0 ng/ml/hr before treatment) decreased from 3.9 ng/ml/hr at 6 months to 1.3 at 1.5 years, whereas PRA remained elevated with ACEI. We speculate that the stronger reduction of PAC contributed to suppression of growth of mesangial matrix and the interstitial fibrosis in the candesartan group.