Endocrine Abstracts (2010) 22 P11

Effects of atenolol add-on treatment on plasma renin activity (PRA) and aldosterone escape in hypertensive patients with diabetes receiving valsartan

Gen Yasuda, Keisuke Yatsu, Nobuhito Hirawa, Yuichiro Yamamoto & Satoshi Umemura

Yokohama Center Hospital, Yokohama, Japan.

Angiotensin II receptor antagonists (ARB) decrease plasma aldosterone concentration (PAC) for cardiovascular protection. However, long-term ARB therapy increases PRA and PAC, which is known as ‘aldosterone escape.’ β-Blockers are the noble antihypertensive agents to decrease PRA. Nevertheless, little is known about the effect of coadministration of both agents on PRA and aldosterone escape. The study was designed to compare the effects of adding atenolol (β-blocker) to valsartan (ARB) and doubling the dose of valsartan in diabetic patients whose blood pressure did not reach the therapeutic goal (140/90 mmHg) by valsartan monotherapy. This study was approved by the local ethical committee. Fifty-four hypertensive patients (62±10 years old, 27 men and 27 women, serum creatinine levels <2 mg/dl) already on valsartan 80 mg/day were assigned to receive either a double dose of valsartan (160 mg) or atenolol (50 mg) added to valsartan (80 mg) for 48 weeks. PRA and PAC were measured. Two groups showed significant decreases (P<0.05) in blood pressure during the treatment period. In the both groups, PAC decreased initially but returned to the baseline level at 24 weeks. PRA decreased in the atenolol add-on group but it increased in the valsartan double-dose group (Table 1). These findings indicate that adding atenolol to valsartan counteracts the PRA-stimulating effects of ARB but aldosterone escape still occurs, suggesting that hyperreninemia caused by the interruption of negative feedback of angiotensin II does not induce aldosterone escape and there is another pathway for maintaining aldosterone secretion in diabetes.

Table 1 Effects of atenolol and valsartan (A+V) or double-dose valsartan (V×2) on PAC and PRA (Mean±S.E.M.; *P<0.05 versus week 0)
0 week4 week12 week24 week48 week
A+V (PAC, pg/ml)108±1597±18*108±14123±15106±12
V×2 (PAC, pg/ml)98±1091±11*90±13*109±1297±10
A+V (PRA, ng/ml per h)3.6±0.61.0±0.6*1.3±0.5*1.2±0.4*1.5±0.5*
V×2 (PRA, ng/ml per h)3.1±0.55.3±1.3*3.3±0.53.6±0.5*4.0±0.7*

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