Atrial natriuretic peptide accounts for increased cGMP in hypoxia-induced hypertensive rat lungs
| Autor: | Ivan F. McMurtry, J. Gutkowska, Robert C. Tyler, David M. Rodman, Nicholas S. Hill, M. Muramatsu, James R. Klinger |
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| Rok vydání: | 1997 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine medicine.medical_specialty Purinones Physiology Hypertension Pulmonary Protoporphyrins Stimulation Nitroarginine Nitric oxide Muscle hypertrophy Rats Sprague-Dawley chemistry.chemical_compound Atrial natriuretic peptide Reference Values Physiology (medical) Internal medicine medicine Animals Enzyme Inhibitors Hypoxia Cyclic GMP Lung Amitrole Hypertrophy Right Ventricular Altitude Immune Sera Cell Biology Catalase medicine.disease Pulmonary hypertension Rats Heme oxygenase Endothelial stem cell Kinetics Endocrinology chemistry Guanylate Cyclase Heme Oxygenase (Decyclizing) Zaprinast Atrial Natriuretic Factor |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 272:L1126-L1132 |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | Perfusate levels of nitric oxide (NO)-containing compounds and guanosine 3',5'-cyclic monophosphate (cGMP) are increased in hypoxia-induced hypertensive rat lungs. To test if increased cGMP was due to NO stimulation of soluble guanylate cyclase (sGC), we examined effects of inhibition of NO synthase with N omega-nitro-L-arginine (L-NNA) on perfusate accumulation of cGMP in physiological salt solution (PSS)-perfused hypertensive lungs isolated from rats exposed for 3-4 wk to hypobaric hypoxia. Because 200 microM L-NNA did not reduce cGMP, we next examined inhibitors of other pathways of stimulation of either sGC or particulate GC (pGC). Neither 5 microM Zn-protophorphyrin, an inhibitor of CO production by heme oxygenase, nor 10 mM aminotriazole, an inhibitor of H2O2 metabolism by catalase, reduced perfusate cGMP. However, an antiserum to atrial natriuretic peptide (ANP; 100 microliters antiserum/30 ml PSS), to inhibit ANP activation of pGC, completely prevented accumulation of the nucleotide. ANP antiserum was also more effective than L-NNA in reducing lung tissue cGMP. In contrast, L-NNA but not ANP antiserum increased resting vascular tone. These results suggested that whereas ANP determined perfusate and tissue levels of cGMP, NO regulated vascular tone. To test if perfusate cGMP reflected ANP stimulation of pGC in endothelial rather than smooth muscle cells, we examined effects of 10 microM Zaprinast, an inhibitor of cGMP hydrolysis in smooth muscle but not endothelial cells, and found no increase of cGMP in hypertensive lungs. ANP levels were not elevated in hypertensive lungs, and it is unclear by what mechanism the ANP-stimulated activity of pGC is increased in hypertensive pulmonary vascular endothelial cells. |
| Databáze: | OpenAIRE |
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