کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1908887 1046691 2011 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Pulmonary hypertension in the newborn GTP cyclohydrolase I-deficient mouse
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Pulmonary hypertension in the newborn GTP cyclohydrolase I-deficient mouse
چکیده انگلیسی

Tetrahydrobiopterin (BH4) is a regulator of endothelial nitric oxide synthase (eNOS) activity. Deficient levels result in eNOS uncoupling, with a shift from nitric oxide to superoxide generation. The hph-1 mutant mouse has deficient GTP cyclohydrolase I (GTPCH1) activity, resulting in low BH4 tissue content. The adult hph-1 mouse has pulmonary hypertension, but whether such condition is present from birth is not known. Thus, we evaluated newborn animals’ pulmonary arterial medial thickness, biopterin content (BH4 + BH2), H2O2 and eNOS, right ventricle-to-left ventricle + septum (RV/LV + septum) ratio, near-resistance pulmonary artery agonist-induced force, and endothelium-dependent and -independent relaxation. The lung biopterin content was inversely related to age for both types, but significantly lower in hph-1 mice, compared to wild-type animals. As judged by the RV/LV + septum ratio, newborn hph-1 mice have pulmonary hypertension and, after a 2-week 13% oxygen exposure, the ratios were similar in both types. The pulmonary arterial agonist-induced force was reduced (P < 0.01) in hph-1 animals and no type-dependent difference in endothelium-dependent or -independent vasorelaxation was observed. Compared to wild-type mice, the lung H2O2 content was increased, whereas the eNOS expression was decreased (P < 0.01) in hph-1 animals. The pulmonary arterial medial thickness, a surrogate marker of vascular remodeling, was increased (P < 0.01) in hph-1 compared to wild-type mice. In conclusion, our data suggest that pulmonary hypertension is present from birth in the GTPCH1-deficient mice, not as a result of impaired vasodilation, but secondary to vascular remodeling.

Figure optionsDownload high-quality image (85 K)Download as PowerPoint slideHighlights
► Tetrahydrobiopterin (BH4) is an endothelial nitric oxide synthase (eNOS) co-factor.
► BH4 deficiency results in eNOS uncoupling and reactive oxygen species generation.
► The hph-1 mutant mouse is congenitally BH4 deficient and pulmonary hypertensive at birth.
► Vascular remodeling is responsible for the high pulmonary vascular resistance in hph-1 mice.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 51, Issue 12, 15 December 2011, Pages 2227–2233
نویسندگان
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