Role of Renal Nerves and Salt Intake on Erythropoietin Secretion in Rats following Carbon Monoxide Exposure
- Cathérine Gebhard,
- Fotios Petroktistis,
- Hua Zhang,
- Daniel Kammerer,
- Christoph Köhle,
- Karin Klingel,
- Margitta Albinus,
- Christoph H. Gleiter,
- Hartmut Osswald and
- Almut Grenz
- Departments of Pharmacology and Toxicology (C.G., H.Z., D.K., C.K., M.A., C.H.G., H.O., A.G.), Oral and Maxillofacial Surgery (F.P.), and Molecular Pathology (K.K.), University Hospital Tuebingen, Tuebingen, Germany
- Address correspondence to:
Dr. Almut Grenz, Department of Pharmacology and Toxicology, University Hospital Tuebingen, D-72074 Tuebingen, Germany. E-mail: almut.grenz{at}uni-tuebingen.de
Abstract
Because the data from the literature contain conflicting results regarding the role of renal nerves and angiotensin II in hypoxia-induced erythropoietin (EPO) secretion, we evaluated the effect of renal nerves and salt intake in rats on EPO secretion stimulated by carbon monoxide (CO). Serum levels and renal mRNA content of EPO were similarly elevated by exposure to different CO concentrations in a dose-dependent manner in rats with bilateral renal denervation (DNX) and in sham-denervated controls (INN). However, at 600 ppm CO, serum concentrations and mRNA of EPO were significantly higher in DNX compared with INN rats (p < 0.05). This increase of EPO secretion in DNX rats could be blocked by administration of neuropeptide Y (NPY) (p < 0.05), whereas the NPY receptor antagonist did not enhance EPO secretion in INN rats after CO exposure. Agonists and antagonists of β-adrenergic receptors had no effect on EPO secretion. High-salt (HS) diet reduced EPO secretory response at 600 ppm CO by 55% compared with INN rats on normal salt diet (p < 0.01). In addition, DNX increased EPO secretion in rats on low-salt and HS diet, whereas plasma renin activity did not correlate with EPO levels under these experimental conditions. In summary, our data suggest that renal nerves contribute to the half-maximal EPO secretory response to CO exposure, possibly via NPY receptors.
Footnotes
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This investigation was supported by Federal Ministry of Education, Science, Research and Technology Grant 01EC0001) and Deutsche Forschungsgemeinschaft Grant SFB-TR 19-04 (to K.K.).
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.106.105973.
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ABBREVIATIONS: EPO, erythropoietin; DNX, bilateral renal denervation; CO, carbon monoxide; NPY, neuropeptide Y; AI, angiotensin I; AII, angiotensin II; PRA, plasma renin activity; HS, high-salt diet; LS, low-salt diet; INN, intact renal innervation; ISO, isoproterenol; PROP, propranolol; ANPY, NPY antagonist; HPLC, high-performance liquid chromatography; HbCO, carboxyhemoglobin; PCR, polymerase chain reaction; NS, normal salt; veh, vehicle.
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- Received April 11, 2006.
- Accepted June 29, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
