里中 弘志

We compared the efficacies of 2 prescriptions, one of a medium-dose angiotensin II receptor blocker （ARB） with high-dose of calcium channel blocker （CCB） and another of medium-dose of ARB with medium-dose of CCB and a thiazide diuretic in 22 hypertensive patients who did not achieve the target blood pressure level with the combination of medium-dose of ARB and medium-dose of CCB. A randomized crossover study was performed giving a fixed combination of 100 mg irbesartan with 10 mg amlodipine or a fixed-dose combination of 100 mg irbesartan with 5 mg amlodipine added by 1 mg trichlormethiazide for 12-16 weeks each. The blood pressure measured in hospital was comparable between the high-dose CCB period （130/77 mmHg） and the thiazide period （130/79 mmHg）. The morning and the evening blood pressures measured at home were also comparable in the high-dose of CCB and the thiazide periods, while the evening heart rate was higher in the thiazide period than in the high-dose CCB period. As for the laboratory data, hemoglobin A1c （＋0.2％, p＝0.013）, serum nonHDL cholesterol （＋12 mg/dL, p＝0.047） and serum uric acid （＋0.8 mg/dL, p＝0.001） were significantly higher in the thiazide period than in the high-dose CCB period. On the other hand, urinary albumin excretion （－28.8％，p＝0.026） and estimated glomerular filtration rate （－5.8％，p＝0.012） were significantly lower in the thiazide period than in the high-dose CCB period. In the combination drug therapy of hypertension, the increase of CCB dose is preferable in preserving renal function and in avoiding adverse effects on metabolisms of glucose, lipid and uric acid.

We compared treatment with a high-dose angiotensin II receptor blocker(ARB)and combination of ARB with a thiazide diuretic in 17 patients with hypertension. A randomized crossover study was performed giving 80 mg telmisartan or fixed-dose combination of 40 mg telmisartan and 12.5 mg hydrochlorothiazide for 16 weeks each. Although the clinic blood pressure was comparable between the high-dose ARB period(134/81 mmHg)and the combination period(134/82 mmHg), the morning home blood pressure was lower in the combination period than in the high-dose ARB period(138/82 vs. 151/88 mmHg, p=0.026/0.013). No significant difference was observed in urinary albumin excretion, but estimated glomerular filtration rate was lower in the combination than in the high-dose ARB period(58.9 vs. 62.1 mL/min/1.73 m^2, p=0.039). Serum uric acid was higher in the combination than in the high-dose ARB period(6.7 vs. 5.9 mg/dL p=0.022). The indices of glucose metabolism, serum lipids, oxidative stress, inflammation and adipocytokine did not significantly differ between the two periods. There was no significant difference in the measurement of endothelium-dependent vasodilation between the two periods. It is suggested that the addition of thiazide diuretic to medium-dose ARB is more effective in lengthening the hypotensive effect than high-dose ARB, however, care should be taken for the elevation of serum uric acid and the decrease in renal function.

内科学（循環器・腎臓）内科学（循環器・腎臓）内科学（循環器・腎臓）内科学（循環器・腎臓)内科学（循環器・腎臓）内科学（循環器・腎臓）内科学（循環器・腎臓）内科学（循環器・腎臓）内科学（循環器・腎臓）内科学（循環器・腎臓）

In the treatment of hypertension, care should be taken for preventing of hypertensive organ injuries as well as lowering blood pressure to the adequate level in order to reduce the risk of cardiovascular diseases. The purpose of this study is to examine the effects of angiotensin II receptor blockers (ARB), calcium channel blockers (CCB) and their combination on the development of cardiovascular organ injuries in spontaneously hypertensive rats (SHR). Four groups of male 8-week-old SHR (n=9 each) were given vehicle(control), 10 mg/kg azelnidipine (AZL), 10 mg/kg olmesartan (OLM, n=9), or the combination of AZL and OLM(5 mg/kg each)for 12 weeks, and their effects on cardiovascular organ injuries were evaluated. Tail-cuff blood at 12 weeks was similarly lowered by AML, OLM and the combination therapy(148, 143 and 143 mmHg, respectively)as compared with the control SHR (198 mmHg). Pulse rate was significantly less in the AZL group but not in the OLM group or the combination therapy group than in the untreated control group (-27, -12, +6 bpm, respectively). The cardiac ventricular weight (AZL -12%, OLM -15%, combination -18% vs. control) and aortic thickness (AZL -17%, OLM -16%, combination -19% vs. control) were reduced by similar extents in the three groups given antihypertensive treatments. Regarding the myocardial fibrosis, left ventricular hydroxyproline content was reduced in the OLM and the combination groups but the change was not significant in the AZL group (AZL -14%,OLM -30%, combination -27% vs. control). In the echocardiographic evaluation of cardiac function, the index of left ventricular diastolic function is significantly improved in the OLM and the combination groups but not in the AZL group, while the index of systolic function was not different between the four groups. It is suggested that the antihypertensive therapy including ARB is superior to the monotherapy by CCB in preventing the myocardial fibrosis and preserving the left ventricular diastolic function.