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Blood pressure profile and response to NG ‐nitro‐L‐arginine methyl ester challenge in conscious TRPV4‐deficient mice
Author(s) -
Nishijima Yoshinori,
Lund Hayley,
Zheng Xiaodong,
Mattson David,
Zhang David
Publication year - 2012
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.26.1_supplement.1056.9
Subject(s) - trpv4 , vasodilation , in vivo , nitric oxide , mean arterial pressure , blood pressure , chemistry , concomitant , basal (medicine) , endocrinology , medicine , pharmacology , heart rate , transient receptor potential channel , biology , receptor , microbiology and biotechnology , insulin
Endothelial TRPV4 is a Ca 2+ entry channel critically involved in endothelium‐mediated dilation in both conduit and resistance vascular beds. However the importance of this TRPV4‐mediated vasodilation in vivo has not been well characterized. We investigated the role of TRPV4 in blood pressure (BP) regulation under normal conditions and in response to a hypertensive challenge. The study was performed in TRPV4‐deficient (TRPV4 −/− ) and wild‐type (WT) mice implanted with a radiotelemetry device for continuous recording of mean arterial pressure (MAP), heart rate (HR) and activity. Basal MAP tends to be lower in TRPV4 −/− mice (101 ± 3 mmHg, n=3, p=0.054) than in WT controls (108 ± 1 mmHg, n=4), whereas HR was comparable in TRPV4 −/− (565 ± 11 bpm) and WT mice (571 ± 8 bpm). Hypertension was induced by administration of L‐NAME (0.5 g/L), a nitric oxide synthase inhibitor, in drinking water for 7 days. The L‐NAME‐induced increase in MAP was similar in TRPV4 −/− (9.8 ± 1.6 %) and WT (9.5 ± 1.6 %), although the concomitant reduction in HR was less in TRPV4 −/− (−7.5 ± 1.1 %) than in WT (−12.6 ± 1.9 %). The activity was lower in TRPV4 −/− (4.1 ± 0.8 units) compared with WT (6.3 ± 1.5 units). In conclusion, TRPV4 −/− mice exhibit a trend toward a lower basal BP but retain a normal BP response to an L‐NAME challenge. These findings call for further evaluation of the significance of TRPV4 in the regulation of vascular tone in vivo.