The combination of valsartan and ramipril protects against blood vessel injury and lowers blood pressure

Abstract

We investigated the anti-hypertensive and vascular protective effects of the combination of valsartan, an angiotensin receptor blocker, and ramipril, an angiotensin-converting enzyme inhibitor. We administered the highest possible equivalent doses of both drugs (averages: 15.3 mg/kg of valsartan and 0.48 mg/kg of ramipril) to spontaneously hypertensive rats (SHRs) (these doses were clinically equivalent to human doses of 160 and 5 mg, respectively). We also administered lower (half) doses of each drug (7.65 mg/kg valsartan and 0.24 mg/kg ramipril). Valsartan and/or ramipril were orally administered to conscious telemetered SHRs, and systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR), were measured. To assess synergistic drug effects in terms of protection against vascular injury, we used the in vivo, cuff-induced, neointimal hyperplasia model in C57BL/6 mice to measure calf serum-induced vascular smooth muscle cell (VSMC) proliferation in vitro and to assess neointimal formation, DNA synthesis, and [³H]-thymidine incorporation. We found that the combination low-dose treatment did not change SBP, but it did reduce the MAP to a similar level as that afforded by valsartan alone. The combination therapy did not significantly alter the HR. Fixed doses of both drugs in combination significantly reduced neointimal formation and the numbers of BrdU-positive cells. However, combination treatment did not reduce VSMC proliferation to a greater extent than that afforded by either drug alone. Thus, combination therapy with lower-dose valsartan and ramipril effectively lowered blood pressure, possibly by inhibiting neointimal formation and DNA synthesis.