What is the clinical evidence from this study?

Study design: Other. Population: Balloon-injury-elicited neointima formation (n=60). Intervention: Valsartan and benazepril combination vs. Vehicle, valsartan alone, or benazepril alone. Primary outcome: Neointima formation (intima/media ratio) (p=<0.05).

January 1, 2004Hypertension Research39 citationsOpen Access

Combined Treatment with an AT1 Receptor Blocker and Angiotensin Converting Enzyme Inhibitor Has an Additive Effect on Inhibiting Neointima Formation via Improvement of Nitric Oxide Production and Suppression of Oxidative Stress

Q: What are the key findings of this study?

Combined treatment with valsartan and benazepril significantly suppressed neointima formation compared to either agent alone, independent of blood pressure reduction.

SYShinji YagiSaitama Medical University TMToshisuke MoritaToho University SKShigehiro KatayamaInstitute for Advanced Study

Key Result

Combined treatment with valsartan and benazepril significantly suppressed neointima formation compared to either agent alone, independent of blood pressure reduction.

Structured PICO

Does combined treatment with valsartan and benazepril reduce neointima formation in a rat model of balloon-injured carotid arteries?

Population

60 male Sprague-Dawley rats subjected to carotid artery balloon injury to evaluate the effects of combined ARB and ACEI treatment on neointima formation over 3 weeks.

Intervention

Combined treatment with valsartan (3 mg/kg/day or 1 mg/kg/day) and benazepril (0.3 mg/kg/day or 0.1 mg/kg/day) administered from 1 week before to 2 weeks after balloon injury.

Comparator

Vehicle control, benazepril alone (0.3 mg/kg/day), or valsartan alone (3 mg/kg/day).

Outcome

Neointima formation (intima/media ratio) at 14 days post-injury.surrogate

Combined ACE inhibitor and ARB therapy additively suppresses neointima formation after vascular injury, likely through complementary effects on nitric oxide production and oxidative stress.

Main Result

p-value: p=<0.05

Limitations

Animal model findings may not fully translate to humans due to differences in local renin-angiotensin system enzymes (e.g., chymase).

Abstract

Accumulating evidence shows that inhibition of the vascular renin-angiotensin system results in suppression of injury-elicited neointima formation. We attempted to determine whether or not combined treatment with an angiotensin II type 1 receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) has an additive inhibitory effect on balloon-injury-elicited neointima formation in the carotid artery. Male Sprague-Dawley rats were treated with an ARB (valsartan: 3 mg/kg/day) and/or an ACEI (benazepril: 0.3 mg/kg/day) from 1 week before until 2 weeks after balloon injury. Experiments were also conducted with one-third of the dose combination used in the original experiments. Both ARB and ACEI inhibited neointima formation without any blood pressure changes. The full-dose combination lowered blood pressure and suppressed neointima formation significantly compared with the levels in the groups treated with either ACEI or ARB alone. The low-dose combination without blood pressure reduction also inhibited neointima formation to a similar extent as the full-dose combination. We measured 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a marker of oxidative stress, and nitrite and nitrate (NOx), an index of nitric monoxide production, in media conditioned by the injured artery. NOx production was lower and 8-iso-PGF2alpha was higher in the media of the injured artery, compared with those in the normal artery. ACEI restored NOx production more dramatically than ARB, and ARB suppressed 8-iso-PGF2alpha markedly compared with ACEI. These results suggest that the combination of an ARB and an ACEI exerts an additive inhibitory effect, presumably through an increase in production and bioavailability of NO from the endothelium.

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