Nitric oxide-cGMP pathway is involved in endotoxin-induced contractile dysfunction in rat hearts
| Autor: | Satoaki Matoba, Kazuko Akashi, Jun Shiraishi, Susumu Nishikawa, Mitsuo Takeda, Miyuki Kobara, Tetsuya Tatsumi, Jun Asayama, Natsuya Keira, Satoshi Yamanaka, Masao Nakagawa, Akiko Mano, Henry Fliss |
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| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Physiology In Vitro Techniques Nitric Oxide Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Ventricular Dysfunction Left Physiology (medical) Internal medicine Medicine Animals Cyclic GMP chemistry.chemical_classification biology business.industry Septic shock Myocardium medicine.disease Myocardial Contraction Rats Nitric oxide synthase Endotoxins Enzyme Endocrinology chemistry Shock (circulatory) Circulatory system biology.protein medicine.symptom business Signal Transduction |
| Zdroj: | Journal of applied physiology (Bethesda, Md. : 1985). 96(3) |
| ISSN: | 8750-7587 |
| Popis: | The mechanisms by which endotoxemia causes cardiac depression have not been fully elucidated. The present study examined the involvement of nitric oxide (NO) in this pathology. Rats were infused with lipopolysaccharide (LPS) or saline, and the plasma and myocardial [Formula: see text] and [Formula: see text] (NOx) concentrations were measured before or 3, 6, and 24 h after treatment. The hearts were then immediately isolated and mounted in a Langendorff apparatus, and left ventricular developed pressure (LVDP) was determined before biochemical analysis of the myocardium. LPS injection effected the expression of inducible NO synthase (iNOS) in the myocardium, a marked increase in plasma and myocardial NOx levels, and a significant decline in LVDP compared with saline controls. The LPS-induced NO production and concomitant cardiac depression were most pronounced 6 h after LPS injection and were accompanied by a significant increase in myocardial cGMP content. Myocardial ATP levels were not significantly altered after LPS injection. Significant negative correlation was observed between LVDP and myocardial cGMP content, as well as between LVDP and plasma NOx levels. Aminoguanidine, an inhibitor of iNOS, significantly attenuated the LPS-induced NOx production and contractile dysfunction. Furthermore, 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase, significantly decreased myocardial cGMP content and attenuated the contractile depression, although aminoguanidine or 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one was not able to completely reverse myocardial dysfunction. Our data suggest that endotoxin-induced contractile dysfunction in rat hearts is associated with NO production by myocardial iNOS and a concomitant increase in myocardial cGMP. |
| Databáze: | OpenAIRE |
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