C-peptide exerts cardioprotective effects in myocardial ischemia-reperfusion
| Autor: | Lindon H. Young, Rosario Scalia, Yasuhiko Ikeda, Allan M. Lefer |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
medicine.medical_specialty Neutrophils Physiology Myocardial Ischemia Ischemia Myocardial Reperfusion Injury In Vitro Techniques Granulocyte Rats Sprague-Dawley Contractility chemistry.chemical_compound Coronary Circulation Physiology (medical) Internal medicine Animals Medicine Cardioprotective Agent Proinsulin C-Peptide business.industry C-peptide Heart medicine.disease Myocardial Contraction Rats medicine.anatomical_structure Endocrinology chemistry Circulatory system Cardiology and Cardiovascular Medicine business Insulin processing |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 279:H1453-H1459 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.2000.279.4.h1453 |
| Popis: | Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in cardiac dysfunction. C-peptide, a cleavage product of proinsulin to insulin processing, induces nitric oxide (NO)-mediated vasodilation. NO is reported to attenuate cardiac dysfunction caused by PMNs after ischemia-reperfusion (I/R). Therefore, we hypothesized that C-peptide could attenuate PMN-induced cardiac dysfunction. We examined the effects of C-peptide in isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with PMNs. C-peptide (70 nmol/kg iv) given 4 or 24 h before I/R significantly improved coronary flow ( P < 0.05), left ventricular developed pressure (LVDP) ( P < 0.01), and the maximal rate of development of LVDP (+dP/d t max) compared with I/R hearts obtained from rats given 0.9% NaCl ( P < 0.01). N G-nitro-l-arginine methyl ester (l-NAME) (50 μmol/l) blocked these cardioprotective effects. In addition, C-peptide significantly reduced cardiac PMN infiltration from 183 ± 24 PMNs/mm2 in untreated hearts to 44 ± 10 and 58 ± 25 PMNs/mm2 in hearts from 4- and 24-h C-peptide-treated rats, respectively. Rat PMN adherence to rat superior mesenteric artery exposed to 2 U/ml thrombin was significantly reduced in rats given C-peptide compared with rats given 0.9% NaCl ( P < 0.001). Moreover, C-peptide enhanced basal NO release from rat aortic segments. These results provide evidence that C-peptide can significantly attenuate PMN-induced cardiac contractile dysfunction in the isolated perfused rat heart subjected to I/R at least in part via enhanced NO release. |
| Databáze: | OpenAIRE |
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