Characterization of blood pressure and endothelial function in TRPV4-deficient mice with L-NAME- and angiotensin II-induced hypertension

Yoshinori Nishijima, Xiaodong Zheng, Hayley Lund, Makoto Suzuki, David L. Mattson, David X. Zhang

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Transient receptor potential vanilloid type 4 (TRPV4) is an endothelial Ca2+ entry channel contributing to endothelium-mediated dilation in conduit and resistance arteries. We investigated the role of TRPV4 in the regulation of blood pressure and endothelial function under hypertensive conditions. TRPV4-deficient (TRPV4-/-) and wild-type (WT) control mice were given L-NAME (0.5 g/L) in drinking water for 7 days or subcutaneously infused with angiotensin (Ang) II (600 ng/kg per minute) for 14 days, and blood pressure measured by radiotelemetry. TRPV4-/- mice had a lower baseline mean arterial pressure (MAP) (12-h daytime MAP, 94 ± 2 vs. 99 ± 2 mmHg in WT controls). L-NAME treatment induced a slightly greater increase in MAP in TRPV4-/- mice (day 7, 13 ± 4%) compared to WT controls (6 ± 2%), but Ang II-induced increases in MAP were similar in TRPV4-/- and WT mice (day 14, 53 ± 6% and 37 ± 11%, respectively, P < 0.05). Chronic infusion of WT mice with Ang II reduced both acetylcholine (ACh)-induced dilation (dilation to 10-5 mol/L ACh, 71 ± 5% vs. 92 ± 2% of controls) and the TRPV4 agonist GSK1016790A-induced dilation of small mesenteric arteries (10-8 mol/L GSK1016790A, 14 ± 5% vs. 77 ± 7% of controls). However, Ang II treatment did not affect ACh dilation in TRPV4-/- mice. Mechanistically, Ang II did not significantly alter either TRPV4 total protein expression in mesenteric arteries or TRPV4 agonist-induced Ca2+ response in mesenteric endothelial cells in situ. These results suggest that TRPV4 channels play a minor role in blood pressure regulation in L-NAMEbut not Ang II-induced hypertension, but may be importantly involved in Ang II-induced endothelial dysfunction.

Original languageEnglish (US)
Article numbere00199
JournalPhysiological reports
Volume2
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • Endothelium
  • Endothelium-derived hyperpolarizing factor
  • Hypertension
  • Mesenteric arteries
  • Nitric oxide
  • TRPV4

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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