Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats

Masahito Kajiya, Masanori Hirota, Yousuke Inai, Takahiko Kiyooka, Taro Morimoto, Tatsuo Iwasaki, Kousuke Endo, Satoshi Mohri, Juichiro Shimizu, Toyotaka Yada, Yasuo Ogasawara, Keiji Naruse, Tohru Ohe, Fumihiko Kajiya

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Pulmonary hypertension (PH) causes right ventricular (RV) hypertrophy and, according to the extent of pressure overload, eventual heart failure. We tested the hypothesis that the mechanical stress in PH-RV impairs the vasoreactivity of the RV coronary microvessels of different sizes with increased superoxide levels. Five-week-old male Sprague-Dawley rats were injected with monocrotaline (n = 126) to induce PH or with saline as controls (n = 114). After 3 wk, coronary arterioles (diameter = 30-100 μm) and small arteries (diameter = 100-200 μm) in the RV were visualized using intravital videomicroscopy. We evaluated ACh-induced vasodilation alone, in the presence of N ω-nitro-L-arginine methyl ester (L-NAME), in the presence of tetraethylammonium (TEA) or catalase with or without L-NAME, and in the presence of SOD. The degree of suppression in vasodilation by L-NAME and TEA was used as indexes of the contributions of endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), respectively. In PH rats, ACh-induced vasodilation was significantly attenuated in both arterioles and small aretries, especially in arterioles. This decreased vasodilation was largely attributable to reduced NO-mediated vasoreactivity, whereas the EDHF-mediated vasodilation was relatively robust. The suppressive effect on arteriolar vasodilation by catalase was similar to TEA in both groups. Superoxide, as measured by lucigenin chemiluminescence, was significantly elevated in the RV tissues in PH. SOD significantly ameliorated the impairment of ACh-induced vasodilation in PH. Robust EDHF function will play a protective role in preserving coronary microvascular homeostasis in the event of NO dysfunction with increased superoxide levels.

Original languageEnglish
Pages (from-to)H2737-H2744
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number6
DOIs
Publication statusPublished - Jun 2007

Keywords

  • Acetylcholine
  • Catalase
  • Endothelium-derived hyperpolarizing factor
  • N-nitro-L-arginine methyl ester
  • Superoxide dimutase
  • Tetraethylanmonium

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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