Is renoprotection by angiotensin receptor blocker dependent on blood pressure?: the Saitama Medical School, Albuminuria Reduction in Diabetics with Valsartan (STAR) study.

To explore the effects of various antihypertensive regimes on microalbuminuria, an angiotensin II receptor blocker (ARB), valsartan, was substituted for or added to treatment with a calcium channel blocker (CCB). After a 6-month CCB baseline period, 28 Japanese hypertensive patients with incipient diabetic nephropathy (defined as a urinary albumin excretion [UAE] of 30-300 mg/g creatinine), were assigned to two groups according to their blood pressure (BP) levels: in patients with a BP of more than 130/85 mmHg (n=17), valsartan was added to the CCB (Group A), while in patients with a BP <130/85 mmHg, valsartan alone was given (Group B: n=11) for 12 months. UAE was determined before and at 3, 6 and 12 months after the initiation of ARB. Although the initial BP was significantly higher in Group A (150/83 mmHg) than Group B (127/77 mmHg), BP was decreased to 141/78 mmHg in Group A and slightly, but not significantly, increased to 130/82 mmHg in Group B. In both groups, UAE was significantly decreased after ARB treatment (to 89% of the basal value in Group A and to 40.5% of the basal value in Group B) and did not differ each other and the amount of decrease did not differ significantly between the two groups. These results suggest that combination therapy with an ARB and CCB is very effective in lowering BP and UAE in cases in which BP is not well controlled, while, even in patients with a sufficient BP control of <130/85 mmHg, the use of ARB singly resulted in a significant decrease in UAE without a further decrease in BP, implying that the ARB had a renoprotective action independent of changes in BP.

Effect of p53 deficiency on external vascular cuff-induced neointima formation.

The p53 tumor suppressor gene may act as an inhibitor of vascular neointima formation in response to injury and in the present study the effects of p53 deficiency on external vascular cuff-induced neointima formation were evaluated. Vascular neointima formation was induced by an external vascular cuff; a polyethylene tube placed around a 2 mm segment of the left femoral artery ensheathed the adventitia, but avoided direct intraluminal injury. Two weeks after cuff placement, the cuff-sheathed and contralateral control arteries without cuff from wild-type (n=10) and p53 deficient (n=8) mice were harvested and analyzed by quantitative morphometry. The areas of the lumen, intima, and media were measured in 10 cross-sections from one edge to the other of the cuffed portion, and in the corresponding 2-mm segment of the contralateral control artery. The volume ratio of the intima to media (I/M) was calculated. The contralateral control arteries without a cuff did not have intima in either wild-type or p53 deficient mice. In the cuff-sheathed arteries, neointima formation of p53 deficient mice with an I/M of 93% was significantly greater than that of wild-type mice with an I/M of 50% (P=0.001). The absence of p53 is associated with increased neointima formation in response to cuff injury.