Hideki Inada

Protective effects of an angiotensin II receptor blocker and a long-acting calcium channel blocker against cardiovascular organ injuries in hypertensive patients.

The purpose of this study is to compare the long-term effects of an angiotensin II receptor blocker (ARB) and a long-acting calcium channel blocker (CCB) on left ventricular geometry, hypertensive renal injury and a circulating marker of collagen synthesis in hypertensive patients. Patients with essential hypertension (24 men and 19 women; age, 37–79 years) were treated with a long-acting CCB, amlodipine (AML; 2.5–7.5 mg once daily) for 6 months. Then, AML was switched to an ARB, candesartan (CS; 4–12 mg once daily), in 22 patients (CS group), while AML was continued in the remaining 21 patients for another 6 months (AML group). At the end of each treatment period, ambulatory blood pressure monitoring (ABPM), echocardiography and sampling of blood and urine were performed. The average office blood pressure during the latter period was comparably controlled in the AML and the CS groups (AML: 130±8/87±7 mmHg; CS: 133±11/88±7 mmHg), while the average systolic blood pressure of 24-h ABPM was significantly lower in the AML than in the CS group (127±9 vs. 133 ±14 mmHg, p<0.05). Consequently, the left ventricular mass index was significantly decreased in the AML group (102±18 to 92±12 g/m2, p<0.05), while the change was insignificant in the CS group (103±25 to 98±21 g/m2). On the other hand, plasma procollagen I C-terminal peptide (PICP), a marker of collagen synthesis, was lowered by CS (86±21 to 70±21 ng/ml, p<0.01), but was not significantly affected by AML (80±127 to 74±91 ng/ml). CS reduced urinary albumin excretion (57±123 to 26±33 mg/g creatinine, p<0.05), but AML did not bring about significant changes (85±27 to 73±19 mg/g creatinine). The results suggested that long-acting CCBs are effective in improving left ventricular hypertrophy by controlling 24-h blood pressure, while ARBs possess protective effects against cardiovascular fibrosis and renal injury beyond their antihypertensive effects.

Urinary excretion of liver fatty acid-binding protein in health-check participants

BackgroundMessenger RNA of liver fatty acid-binding protein (L-FABP) is expressed in proximal tubules of the kidney, and a certain amount is excreted into urine. We analyzed factors relating to the urinary L-FABP excretion in health-check participants.MethodsWe measured L-FABP in the first morning urine by ELISA in 715 men and 193 women 30–79 years of age who entered a 2-day hospitalized health checkup program. In addition to the routine physical examination and laboratory tests, plasma high-sensitivity C-reactive protein (HSCRP) was assayed.ResultsIn 150 healthy subjects, urinary L-FABP averaged 3.6 ± 0.2 µg/g creatinine, whereas the values were significantly increased in patients with hypertension (5.2 ± 0.4, P = 0.010), diabetes mellitus (5.5 ± 0.5, P < 0.001), and chronic hepatitis (5.8 ± 1.0, P = 0.022). Urinary L-FABP excretion was significantly greater in women than in men when the value was related to creatinine. In regression analysis in men, urinary L-FABP was positively correlated with fasting plasma glucose (r = 0.103, P = 0.033) and plasma HSCRP (r = 0.135, P = 0.006).ConclusionsIt is suggested that renal production and urinary excretion of L-FABP are increased in situations in which arteriosclerosis is promoted, such as hypertension, diabetes mellitus, and cardiovascular inflammation.

Effects of Valsartan on the Progression of Chronic Renal Insufficiency in Patients with Nondiabetic Renal Diseases

The present study tested the effects of valsartan, an angiotensin II receptor blocker, on the progression of renal insufficiency in patients with nondiabetic renal diseases. The study subjects were 22 patients with nondiabetic renal diseases whose serum creatinine (Cr) ranged from 1.5 to 3.0 mg/dl. Valsartan (40–80 mg) or placebo was given once daily for 1 year each in a random crossover manner. In both periods, antihypertensive medications were titrated when the blood pressure was not lower than 140/90 mmHg. Blood sampling and urinalysis were performed bimonthly throughout the study periods. The average blood pressure was comparable between the valsartan and the placebo periods (130±9/86 ±6 vs. 131±8/86±6 mmHg). Serum Cr significantly increased from 1.9±0.5 to 2.3±0.8 mg/dl (p<0.001) during the placebo period, but the change was insignificant in the valsartan period (2.1±0.6 to 2.2±0.9 mg/dl). The slope of decrease in the reciprocal of serum Cr was steeper in the placebo period than in the valsartan period (−0.064 ±0.070/year vs. −0.005±0.050/year, p<0.01). During the valsartan period, urinary protein excretion was less than that during the placebo period (0.75±0.73 vs. 1.24±0.92 g/g Cr, p<0.001). Serum K was significantly higher in the valsartan period than in the placebo period (4.6±0.5 vs. 4.4±0.5 mEq/l, p<0.05); however, no patients discontinued taking valsartan as a result of hyperkalemia. It is possible that long-term treatment with an angiotensin II receptor blocker, valsartan, is effective at retarding the deterioration of renal function in patients with nondiabetic renal disease by a mechanism independent of blood pressure reduction.

COMPARISON OF THE EFFECTS OF AMLODIPINE AND LOSARTAN ON 24-HOUR AMBULATORY BLOOD PRESSURE IN HYPERTENSIVE PATIENTS

Effects of amlodipine (AML), a long-acting calcium antagonist, and losartan (LOS), an angiotensin II receptor antagonist, on 24-hr blood pressure profile were compared in 15 patients with essential hypertension. After 4 weeks of placebo period, the patients were treated with AML or LOS in a random cross-over design for 12–16 weeks each. Either drug was given once daily at 0800 and the doses were titrated so that the office blood pressure was reduced lower than 140/90 mmHg. At the end of each period, 24-hr blood pressure was monitored. Average office blood pressure was lowered from 158 ± 2/ 98 ± 2 mmHg to 134 ± 1/87 ± 1 mmHg by AML and 134 ± 2/88 ± 1 mmHg by LOS. Average 24-hr blood pressure was also reduced from 144 ± 3/ 92 ± 2 mmHg to 131 ± 2/84 ± 2 mmHg by AML and 135 ± 3/85 ± 2 mmHg by LOS. The averaged 24-hr systolic blood pressure was significantly lower in AML than in LOS (p < 0.05). Then, the 24-hr blood pressure was analyzed for four segments; morning (0530–0900 h), daytime (0930–1800 h), evening (1830–2300 h) and night (2330–0500 h). Although the daytime blood pressure was comparable between AML and LOS, systolic blood pressure in the evening and morning hours were lower in AML than in LOS (133 ± 2 vs. 138 ± 3 mmHg, p < 0.01; 129 ± 3 vs. 134 ± 4, p < 0.05). Trough to peak ratio of antihypertensive effect on systolic blood pressure was significantly greater in AML than in LOS (62 ± 5% vs. 55 ± 4%, p < 0.05). Either drug did not cause reflective increase in pulse rate over 24 hours. These results suggest that both AML and LOS are equally effective in lowering daytime blood pressure without eliciting reflex tachycardia, however, the antihypertensive effect of AML lasts longer than that of LOS. Such information seems important to achieve 24-hr blood pressure control using these drugs.