Nitric Oxide/cGMP-Independent Vasorelaxation Enhanced by L-Arginine

L-Arginine의 산화질소생성과 무관한 혈관이완효과

  • 문승호 (전남대학교 의과대학 흉부외과학교실) ;
  • 이종은 (전남대학교 의과대학 생리학교실) ;
  • 유광재 (전남대학교 의과대학 생리학교실) ;
  • 오봉석 (전남대학교 의과대학 흉부외과학교실) ;
  • 이동준 (전남대학교 의과대학 흉부외과학교실)
  • Published : 1998.02.01

Abstract

It has not been clear whether L-arginine plays solely a role contributing to vascular nitric oxide (NO) synthesis. To investigate the mechanisms by which L-arginine induces vasorelaxation, effects of L-arginine on the isometric tension, and tissue NOx and cyclic guanosine monophosphate(cGMP) contents were examined in the isolated rat thoracic aorta. L-Arginine induced a dose-dependent relaxation of aortic rings only with intact endothelium only. The vasorelaxation response to low concentrations of L-arginine was abolished by the pretreatment with NG-nitro-L-arginine methyl ester(L-NAME, 10-4 mol/L), whereas the relaxation caused by higher concentrations L-arginine(10-5-10-3 mol/L) was maintained and even more pronounced in the presence of L-NAME. L-Arginine did not affect the vascular tension precontracted with KCl. The vascular tissue contents of NOx/cGMP were not significantly affected by L-arginine, while they were decreased by L-NAME. L-Arginine could not completely recover the NOx/cGMP decreased by L-NAME. Methylene blue only partially antagonized the relaxation response to L-arginine. Indomethacin did not affect the L-arginine-induced vasorelaxation, whereas ouabain markedly attenuated the relaxation. It is suggested that L-arginine induces vasorelaxation not only through its contribution to NO synthesis, but also through enhancing another endothelium-dependent mechanism which is NO/cGMP-independent and cyclooxygenase- independent.

L-Arginine이 산화질소 생성의 전구물질로서 공헌하는 것 이외에 다른 기전에 의하여도 혈관이완을 일으키는가 구명하기 위하여 적출 흰쥐 흉부대동맥 표본에서 L-arginine에 의한 장력, 조직 산화질소 및 cGMP 함량 변동 등을 조사하여 다음과 같은 결과를 얻었다. 1. Phenylephrine(3.5$\times$10-6 mol/L) 수축 대동맥 표본은 L-arginine(10-9~10-3 mol/L)에 의해 용량의존 이완되었다. NG-Nitro-L-arginine methyl ester(L-NAME, 10-5 mol/L) 전처치에 의해 저농도 L-arginine(10-9~10-6 mol/L)에 혈관이완 효과는 소실되었으나 고농도 L-arginine(10-4~10-3 mol/L)의 이완효과는 도리어 증강되었다. 내피층 파괴 혈관 표본은 L-arginine에 대해 이완반응을 보이지 않았다. 2. L-NAME(10-5 mol/L) 존재하에 일어나는 L-arginine 이완효과는 indomethacin 전처치에 의해 영향받지 않으나, ouabain 전처치에 의해 유의하게 감약되었다. 또한 L-arginine 이완효과는 methylene blue에 의해 부분적으로 길항되었다. KCl(3.5$\times$10-2 mol/L) 수축 대동맥 표본은 L-arginine(10-9~10-3 mol/L)에 의해 L-NAME (10-5 mol/L) 처치와 무관하게 이완반응을 보이지 않았다. 3. L-NAME는 혈관조직 산화질소 함량을 감소시키며 이 감소효과는 L-arginine(10-4 mol/L)에 의해 영향받지 않았다. 또한 L-NAME는 혈관조직 cGMP 함량을 감소시키나 이 감소효과는 L-arginine에 의해 영향받지 않았다. 이상의 실험성적은 L-arginine이 내피세포의 산화질소 및 cGMP 생성과 무관한 기전을 통해서도 내피의존 혈관이완효과를 나타냄을 시사하였다.

Keywords

References

  1. Br J Pharmacol v.101 Regional hemodynamic changes during oral ingestion of $N^G$-monomethyl-L-arginine or L-NAME in conscious Brattle rats Gardiner SM;Compton AM;Bennett T;Palmer RMJ;Moncada S
  2. Guidelines Dimethyl L-arginine has digitalis-like activity Nagai K;Hashida A;Nakagawa H;Mori A(ed.);Cohen BD(ed.);Koide H(ed.)
  3. J Clin Invest v.88 L-Arginine abrogates salt-sensitive hypertension in Dahl/Rapp rats Chen PY;Sanders PW
  4. J Cardiovasc Pharmacol v.20 no.SUP.12 L-Arginine as an antihypertensive agent Hashikawa K;Nakaki T;Suzuki H;Kato R;Saruta T
  5. Am J Physiol v.259 L-Arginine-dependent vascular smooth muscle relaxation and cGMP formation Gold ME;Wood KS;Byrns RE;Buga GM;Ignarro LJ
  6. Circ Res v.68 L-Arginine evokes both endothelium-dependent and -independent relaxations in L-Arginine-depleted aortas of the rat Schini VB;Vanhoutte PM
  7. J Cardiovasc Pharmacol v.24 Is guanidino succinate a precursor for nitric oxide synthesis in rat vascular tissue? Richard V;Henry JP;Thuillez C
  8. J Appl Physiol v.74 $N^G$-monomethyl-L-arginine paradoxycally relaxes preconstricted canine intrapulmonary arteries Tseng CM;Goodman LW;Rubin LJ;Tod ML
  9. J Pharmacol Exp Ther v.260 Interaction of non-arginine compounds with the endothelium-derived relaxing factor inhibitor, NG-mononethyl L-arginine Thomas G;Ramwell PW
  10. Circ Res v.64 Release of different r elaxing factors by cultured porcine endothelial cells Boulanger C;Hendricksen H;Lorenz RR;Vanhoutte PM
  11. Biochem Biophys Res Commun v.153 L-Arginine is the physiologic precursor for the formation of nitric oxide in endothelium-dependent relaxation Palmer RMJ;Rees DD;Ashton DS;Moncada S
  12. J Clin Invest v.90 Endothelium-dependent inhibition of $Na^+ -K^+$ATPase activity in rabbit aorta by hyperglycemia : possible role of endothelium-derived nitric oxide Gupta S;Sussman I;McArthur CS;Tornheim K;Cohen RA;Ruderman NB
  13. J Physiol v.402 Passive electrical properties and electrogenic sodium transport of cultured guinea-pig coronary endothelial cells Daut J;Mehrke G;Nees S;Newman WH
  14. Jpn Cir J v.56 Endothelium-derived hyperpolarizing factor Suzuki H;Chen G;Yamamoto Y