Korean Journal of Veterinary Research (대한수의학회지)

The Korean Society of Veterinary Science (대한수의학회)
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Mechanism of the relaxant action of imipramine in isolated rat aorta

흰쥐 대동맥에서 imipramine의 혈관이완 작용기전

  • Kang, Hyung-sub (Bio-Safety Research Institute, Chonbuk National University) ;
  • Lee, Sang-woo (Bio-Safety Research Institute, Chonbuk National University) ;
  • Baek, Sung-su (Bio-Safety Research Institute, Chonbuk National University) ;
  • Joe, Sung-gun (Bio-Safety Research Institute, Chonbuk National University) ;
  • Kim, Jin-shang (Bio-Safety Research Institute, Chonbuk National University)
  • 강형섭 (전북대학교 생체안전성연구소) ;
  • 이상우 (전북대학교 생체안전성연구소) ;
  • 백성수 (전북대학교 생체안전성연구소) ;
  • 조성건 (전북대학교 생체안전성연구소) ;
  • 김진상 (전북대학교 생체안전성연구소)
  • Accepted : 2003.12.01
  • Published : 2003.12.25
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Abstract

Although the antidepressant effects of imipramine (IMI) have been well known in several studies, the effects on cardiovascular system, particularly the vasorelaxant effects, have not known clearly. We hypothesis that IMI-induced vasorelaxation involves NO (nitrie oxide), activation of guanylate cyclase (GC) and $Ca^{2+}$ channel. The possible roles of the endothelium and $Ca^{2+}$ in IMI-induced responses were investigated using isolated rings of rat thoracic aorta and anesthesized rats. In KCl-precontracted rings. IMI produces endothelium-dependent and endothelium-independent relaxations in intact (+E) as well as endothelium-denuded (-E) rat aorta in a concentration-dependent manner. In phenylephrine (PE)-precontracted rings, the IMI-induced relaxation was significantly greater in +E rings. The IMI-induced relaxations were suppressed by nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L-arginine (L-NNA), N(omega)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine, a non-selective GC inhibitor, methylene blue, $Na^+$ channel blockers, lidocaine and procaine, or $Ca^{2+}$ channel blockers, nifedipine and verapamil, in PE-precontracted +E rings, but not in PE-precontracted -E rings. These relaxations were also suppressed by lidocaine or procaine in -E aortic rings. However, IMI-induced relaxations were not inhibited by a PLC inhibitor 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate (NCDC), an inositol monophosphatase inhibitor, lithium, indomethacin and dexamethasone in +E and -E rings. In vivo, infusion of IMI elicited significant decrease in arterial blood pressure. After intravenous injection of saponin, NOS inhibitors. MB and nifedipine, infusion of IMI inhibited the IMI-lowered blood pressure markedly. These findings suggest that the endothelium-dependent relaxation induced by IMI is mediated by activation of NO/cGMP signaling cascade or inhibition of $Ca^{2+}$ entry through voltage-gated channel, and this mechanism may contribute to the hypotensive effects of IMI in rats.

Keywords

References

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