Premium
TRPC1 contribute to hypoxic pulmonary hypertension and right heart hypertrophy: evidence from TRPC1 knockout mice
Author(s) -
Yang XiaoRu,
Cao YuanNing,
Birnbaumer Lutz,
Sham James S.K.
Publication year - 2009
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.23.1_supplement.619.2
Subject(s) - trpc , trpc1 , trpc3 , right ventricular hypertrophy , transient receptor potential channel , medicine , endocrinology , trpc6 , hypoxic pulmonary vasoconstriction , hypoxia (environmental) , vasoconstriction , pulmonary hypertension , chemistry , receptor , organic chemistry , oxygen
Prolonged exposure to aveolar hypoxia causes pulmonary hypertension (PAH) and right heart hypertrophy. Hypoxic PAH is associated with alterations in Ca 2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs). We have previously shown that the store‐operated TRPC1 and receptor‐operated TRPC6 channels are upregulated in PASMCs of chronic hypoxic rats; and the enhanced store‐operated Ca 2+ entry is responsible for the elevated [Ca 2+ ] i and vascular tone in pulmonary arteries (PAs). In this study, we used trpc1 −/− and trpc6 −/− mice to examine whether these channels are required for the development of hypoxic PAH. Real‐time RT‐PCR showed that TRPC1, TRPC2, TRPC3, TRPC4 and TRPC6 channels were expressed in wild‐type mouse PASM. There was no significant shift in the expression of other TRPC subtypes in PAs, except the absence of TRPC1 and TRPC6 transcripts in the trpc1 −/− and trpc6 −/− mice, respectively. In PA and aorta of trpc1 −/− mice, store‐operated Ca 2+ entry induced by cyclopiazonic acid was slightly reduced, suggesting that TRPC1 and other channels were involved. Phenylephrine and serotonin induced vasoconstriction were unaltered in trpc1 −/− PAs and aorta. However, when trpc1 −/− mice were exposed to 4 weeks of hypoxia (10% or 8.5% O 2 ), right ventricular systolic pressure (RVSP) and right heart mass ratio (RV/(LV+S)) was significantly attenuated. There was no significant difference in RVSP and RV/(LV+S) between chronic hypoxic trpc6 −/− and wild‐type mice. These results, for the first time, suggest that TRPC1 might play a significant role in the development of hypoxic PAH and right heart hypertrophy.