Diabetic cardiomyopathy, involving both cardiomyocytes and the sensory and autonomic cardiac innervation, is a major life-threatening complication in diabetes mellitus. Here, we induced long-term (26-53 weeks) diabetes in rats by streptozotocin injection and analyzed the major cardiac neuropeptide signaling system, neuropeptide Y (NPY) and its receptors Y1R and Y2R. Heart compartments and ganglia supplying sympathetic (stellate ganglion) and spinal sensory fibers (upper thoracic dorsal root ganglia=DRG) were analyzed separately by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Ventricular, but not atrial innervation density by NPY-immunoreactive fibers was diminished, and preproNPY expression was transiently (26 weeks) reduced in left atria, but remained unchanged in sympathetic neurons and was not induced in DRG neurons. In all ganglia and heart compartments, Y1R expression dominated over Y2R, and Y1R-immunoreactivity was observed on cardiomyocytes and neuronal perikarya. Atrial, but not ventricular Y1R expression was up-regulated after 1 year of diabetes. Collectively, these data show that a disturbance of the cardiac NPY-Y1R/Y2R signaling system develops slowly in the course of experimentally induced diabetes and differentially affects atria and ventricles. This is in parallel with the clinically observed imbalances of the cardiac autonomic innervation in diabetic cardiac autonomic neuropathy.
- MeSH
- časové faktory MeSH
- experimentální diabetes mellitus chemicky indukované patologie MeSH
- financování organizované MeSH
- ganglion stellatum metabolismus MeSH
- krysa rodu rattus MeSH
- myokard metabolismus MeSH
- neuropeptid Y genetika metabolismus MeSH
- potkani Wistar MeSH
- receptory neuropeptidu Y genetika metabolismus MeSH
- regulace genové exprese fyziologie účinky léků MeSH
- spinální ganglia metabolismus MeSH
- streptozocin MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- MeSH
- chronická nemoc MeSH
- diabetes mellitus 1. typu komplikace MeSH
- exprese genu MeSH
- finanční podpora výzkumu jako téma MeSH
- kardiomyopatie MeSH
- krysa rodu rattus MeSH
- messenger RNA genetika MeSH
- modely nemocí na zvířatech MeSH
- neuropeptid Y fyziologie MeSH
- receptory neuropeptidů MeSH
- srdce MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- MeSH
- experimenty na zvířatech statistika a číselné údaje MeSH
- financování organizované MeSH
- fluorescenční protilátková technika metody statistika a číselné údaje využití MeSH
- imunohistochemie metody statistika a číselné údaje MeSH
- infarkt myokardu farmakoterapie genetika prevence a kontrola MeSH
- krysa rodu rattus MeSH
- melanocyty stimulující hormony analýza diagnostické užití MeSH
- myši chirurgie MeSH
- receptory kalcitoninu krev metabolismus účinky léků MeSH
- srdce účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- myši chirurgie MeSH
- zvířata MeSH
Calcitonin gene-related peptide (CGRP) is a vasorelaxant and positive inotropic and chronotropic peptide that binds to the calcitonin receptor-like receptor. In the heart, upon stimulation CGRP is released from sensory nerve terminals and improves cardiac perfusion and function. In the present study, we investigated alterations in the components of the CGRP signaling system during development of diabetic cardiomyopathy. Rats received a single injection of streptozotocin. Four, 8, and 16 weeks thereafter cardiac CGRP content (radioimmunoassay), calcitonin receptor-like receptor expression (by real-time RT-PCR), and CGRP and calcitonin receptor-like receptor tissue distribution (immunohistochemistry) were assessed. CGRP content of atria and ventricles progressively increased during the 4 months following streptozotocin-treatment, while the distribution of CGRP-immunoreactive fibers was not visibly altered. Conversely, cardiac expression of calcitonin receptor-like receptor initially (4 weeks after treatment) increased but then gradually declined to 47% of control levels in both atria after 16 weeks. These quantitative changes were not associated with altered cellular distribution patterns (primarily in venous and capillary endothelium). Since sensory neurons have been reported to decrease expression of the CGRP precursor in the course of diabetes, the intra-axonal accumulation of CGRP observed here reflects impaired release, which, coupled with the down-regulation of its cognate receptor, calcitonin receptor-like receptor, may contribute to the well-documented impairment of cardioprotective functions in diabetes.
- MeSH
- analýza rozptylu MeSH
- axony metabolismus MeSH
- časové faktory MeSH
- experimentální diabetes mellitus komplikace metabolismus MeSH
- financování organizované MeSH
- funkční lateralita MeSH
- imunohistochemie metody MeSH
- kardiomyopatie etiologie metabolismus MeSH
- krysa rodu rattus MeSH
- messenger RNA metabolismus MeSH
- peptid spojený s genem pro kalcitonin metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- potkani Wistar MeSH
- radioimunoanalýza metody MeSH
- receptory peptidu se vztahem ke genu kalcitoninu metabolismus MeSH
- regulace genové exprese genetika účinky záření MeSH
- srdeční komory mikrobiologie MeSH
- srdeční síně metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- acetylcholin metabolismus MeSH
- adenosintrifosfát metabolismus MeSH
- cholin-O-acetyltransferasa metabolismus MeSH
- corpora paraaortica cytologie metabolismus MeSH
- finanční podpora výzkumu jako téma MeSH
- imunohistochemie MeSH
- karotická tělíska metabolismus MeSH
- katecholaminy metabolismus MeSH
- membránové transportní proteiny metabolismus MeSH
- morčata MeSH
- potkani Wistar MeSH
- serotonin metabolismus MeSH
- synaptofysin metabolismus MeSH
- synthasa oxidu dusnatého metabolismus MeSH
- tyrosin-3-monooxygenasa metabolismus MeSH
- vezikulární transportní proteiny MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- zvířata MeSH
