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Overexpression of the Tissue Renin‐Angiotensin System Causes Pulmonary Hypertension (PH) in TG(mRen2)27 Rat
Author(s) -
DeMarco Vincent Gerard,
Habibi Javad,
Heller Randall L,
Schneider Rebecca I,
WhaleyConnell Adam T,
Hayden Melvin R,
Sowers James R,
Kevin Dellsperger C
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1252
Subject(s) - medicine , endocrinology , pulmonary hypertension , oxidative stress , renin–angiotensin system , nadph oxidase , lung , angiotensin ii , reactive oxygen species , oxidase test , chemistry , blood pressure , enzyme , biochemistry
Background : The Ren2 transgenic rat overexpresses the mouse renin gene in extra‐renal tissues leading to hypertension as a consequence of tissue angiotensin II overexpression and oxidative stress. Little attention focuses on the abnormal expression of the intrapulmonary renin‐angiotensin system (RAS) as a cause or accelerating factor of pulmonary PH. Here we test the hypothesis that intrapulmonary RAS overexpression leads to PH.Methods: We measured right ventricular systolic pressure (RVSP) under anesthesia and performed morphometric analysis on the small pulmonary arteries (PAs) of 8 to 9 wk old male Ren2 and SD rats. Reactive oxygen species (ROS) in whole lung homogenates and NADP(H) oxidase activity in plasma membrane extracts of whole lung homogenates were also measured.Results: Mean (±SEM) RVSP of Ren2 rats was 63 mmHg (±7) compared to 36 (±2) in SD rats (P<0.01). The mean surface area of the vascular wall of small PAs was 38% greater (P<0.001) and the luminal surface area was 54% less (P<0.001) in Ren2 rats compared to SD rats. There was a trend toward higher ROS (P=0.06) and an elevation in NADP(H) oxidase activity in the Ren2 rat (P<0.05).Conclusions: The lungs of male Ren2 rats exhibit oxidative stress, medial thickening of small PAs and moderate to severe PH. Activation of the RAS and downstream signaling contribute to development of PH. Support provided by Children’s Miracle Network and NIH.