| First Author | Belik J | Year | 2011 |
| Journal | Free Radic Biol Med | Volume | 51 |
| Issue | 12 | Pages | 2227-33 |
| PubMed ID | 21982896 | Mgi Jnum | J:179296 |
| Mgi Id | MGI:5301755 | Doi | 10.1016/j.freeradbiomed.2011.09.012 |
| Citation | Belik J, et al. (2011) Pulmonary hypertension in the newborn GTP cyclohydrolase I-deficient mouse. Free Radic Biol Med 51(12):2227-33 |
| abstractText | 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), H(2)O(2) 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 H(2)O(2) 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. |
