Inhibition of nitric oxide synthesis aggravates myocardial ischemia in hemorrhagic shock in constant pressure model

Takeshi Adachi, Shingo Hori, Koji Miyazaki, Masahiro Nakagawa, Soshin Inoue, Yozo Ohnishi, Hiroe Nakazawa, Naoki Aikawa, Satoshi Ogawa

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


In hemorrhagic shock (HS), nitric oxide synthase (NOS) inhibitor is known to increase blood pressure and prolong survival time. On the other hand, NOS inhibitor decreases coronary flow and worsens myocardial ischemia. Therefore, we hypothesized that the beneficial effect of NOS inhibitor is attributable to the increased coronary perfusion pressure and that it outcompetes the coronary vasodilating effects of nitric oxide. To investigate the direct effect of NOS inhibitor on the regulation of coronary circulation and the induction of myocardial ischemia in HS, we used a canine model at a constant aortic pressure of 40 mmHg with an aortic reservoir. In seven dogs, intravenous administration of Nω-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg) at 10 min after induction of HS increased both systemic and coronary vascular resistances and further increased the serum catecholamine concentration at 10 min after L-NAME. In another 14 dogs, the beating hearts were rapidly cross-sectioned (120 ms) and freeze clamped (-190°C) by a specially developed sampling device after 10 min of HS. Transmurally distributed myocardial ischemia was visualized by the enhanced reduced nicotinamide adenine dinucleotide fluorescence, which was significantly increased with L-NAME (n = 7). Chemical analysis revealed a decrease in the myocardial ATP concentration with L-NAME in the subendocardial ischemic region in HS. In conclusion, with the use of an aortic reservoir to keep the aortic pressure constant in HS, NOS blockade significantly worsened myocardial ischemia by decreasing coronary flow and augmenting the serum catecholamine concentration.

Original languageEnglish
Pages (from-to)204-209
Number of pages6
Issue number3
Publication statusPublished - 1998 Mar
Externally publishedYes

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine


Dive into the research topics of 'Inhibition of nitric oxide synthesis aggravates myocardial ischemia in hemorrhagic shock in constant pressure model'. Together they form a unique fingerprint.

Cite this