کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2562966 1127330 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Therapeutic modulation of the nitric oxide: all ace inhibitors are not equivalent
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Therapeutic modulation of the nitric oxide: all ace inhibitors are not equivalent
چکیده انگلیسی

The properties of the angiotensin-converting enzyme (ACE) inhibitors have largely been attributed to a class effect. However, this opinion is now increasingly challenged in view of the findings from recent clinical trials, which have demonstrated differential effects of ACE inhibitors, in particular with respect to secondary cardiovascular prevention outcomes. In this experimental study, Sprague-Dawley rats were treated with five different ACE inhibitors (enalapril, perindopril, quinapril, ramipril, and trandolapril) at equihypotensive doses.All ACE inhibitors increased endothelial nitric oxide synthase (eNOS) protein expression and activity in the aorta (both P < 0.0001 versus vehicle) and in cardiac myocytes (both P < 0.05 versus vehicle). A highly significant effect was observed with perindopril when compared with vehicle in the modulation of eNOS protein expression and activity in aorta (22.52 ± 1.09 versus 9.12 ± 0.57 AU μg−1 protein and 1.59 ± 0.03 versus 0.77 ± 0.02 pmol l−1 citrulline min−1 mg protein−1, respectively) and in cardiac myocytes (17.64 ± 0.94 versus 11.30 ± 0.59 AU μg−1 protein and 0.93 ± 0.02 versus 0.62 ± 0.03 pmol l−1 citrulline min−1 mg protein−1, respectively). On the basis of the eNOS protein expression in the rat aorta, the other ACE inhibitors had similar, but lower effects. Indeed, the rank of potency – based both on eNOS protein expression and activity – was perindopril > trandolapril ≈ quinapril ≈ ramipril ≈ enalapril (P < 0.05 perindopril versus trandolapril and ramipril and P < 0.01 perindopril versus enalapril, respectively).Levels of circulating nitrite/nitrate, the end-metabolites of nitric oxide, were also significantly affected by ACE inhibition, with the same order of potency.Our findings provide further evidence in favor of differential effects associated with ACE inhibitor therapy and suggest that the clinical benefits associated with these drugs may not solely reflect a class effect extending their benefit beyond blood pressure-lowering effect.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacological Research - Volume 56, Issue 1, July 2007, Pages 42–48
نویسندگان
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