Leptin Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by Angiotensin II through Nitric Oxide-Dependent Mechanisms
Objective. This study was designed to investigate whether leptin modifies angiotensin (Ang) II-induced proliferation of aortic vascular smooth muscle cells (VSMCs) from 10-week-old male Wistar and spontaneously hypertensive rats (SHR), and the possible role of nitric oxide (NO). Methods. NO and NO s...
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2010/105489 |
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| author | Amaia Rodríguez Javier Gómez-Ambrosi Victoria Catalán Ana Fortuño Gema Frühbeck |
| author_facet | Amaia Rodríguez Javier Gómez-Ambrosi Victoria Catalán Ana Fortuño Gema Frühbeck |
| author_sort | Amaia Rodríguez |
| collection | DOAJ |
| description | Objective. This study was designed to investigate whether leptin modifies angiotensin (Ang) II-induced proliferation of aortic vascular smooth muscle cells (VSMCs) from 10-week-old male Wistar and spontaneously hypertensive rats (SHR), and the possible role of nitric oxide (NO). Methods. NO and NO synthase (NOS) activity were assessed by the Griess and 3H-arginine/citrulline conversion assays, respectively. Inducible NOS (iNOS) and NADPH oxidase subutnit Nox2 expression was determined by Western-blot. The proliferative responses to Ang II were evaluated through enzymatic methods. Results. Leptin inhibited the Ang II-induced proliferative response of VSMCs from control rats. This inhibitory effect of leptin was abolished by NOS inhibitor, NMMA, and iNOS selective inhibitor, L-NIL, and was not observed in leptin receptor-deficient fa/fa rats. SHR showed increased serum leptin concentrations and lipid peroxidation. Despite a similar leptin-induced iNOS up-regulation, VSMCs from SHR showed an impaired NOS activity and NO production induced by leptin, and an increased basal Nox2 expression. The inhibitory effect of leptin on Ang II-induced VSMC proliferation was attenuated. Conclusion. Leptin blocks the proliferative response to Ang II through NO-dependent mechanisms. The attenuation of this inhibitory effect of leptin in spontaneous hypertension appears to be due to a reduced NO bioavailability in VSMCs. |
| format | Article |
| id | doaj-art-78d18c9f80324423bfc5a92a03b60372 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-78d18c9f80324423bfc5a92a03b603722025-02-03T06:44:47ZengWileyMediators of Inflammation0962-93511466-18612010-01-01201010.1155/2010/105489105489Leptin Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by Angiotensin II through Nitric Oxide-Dependent MechanismsAmaia Rodríguez0Javier Gómez-Ambrosi1Victoria Catalán2Ana Fortuño3Gema Frühbeck4Metabolic Research Laboratory, University of Navarra, 31008 Pamplona, SpainMetabolic Research Laboratory, University of Navarra, 31008 Pamplona, SpainMetabolic Research Laboratory, University of Navarra, 31008 Pamplona, SpainDivision of Cardiovascular Sciences, Center for Applied Medical Research, University of Navarra, 31008 Pamplona, SpainMetabolic Research Laboratory, University of Navarra, 31008 Pamplona, SpainObjective. This study was designed to investigate whether leptin modifies angiotensin (Ang) II-induced proliferation of aortic vascular smooth muscle cells (VSMCs) from 10-week-old male Wistar and spontaneously hypertensive rats (SHR), and the possible role of nitric oxide (NO). Methods. NO and NO synthase (NOS) activity were assessed by the Griess and 3H-arginine/citrulline conversion assays, respectively. Inducible NOS (iNOS) and NADPH oxidase subutnit Nox2 expression was determined by Western-blot. The proliferative responses to Ang II were evaluated through enzymatic methods. Results. Leptin inhibited the Ang II-induced proliferative response of VSMCs from control rats. This inhibitory effect of leptin was abolished by NOS inhibitor, NMMA, and iNOS selective inhibitor, L-NIL, and was not observed in leptin receptor-deficient fa/fa rats. SHR showed increased serum leptin concentrations and lipid peroxidation. Despite a similar leptin-induced iNOS up-regulation, VSMCs from SHR showed an impaired NOS activity and NO production induced by leptin, and an increased basal Nox2 expression. The inhibitory effect of leptin on Ang II-induced VSMC proliferation was attenuated. Conclusion. Leptin blocks the proliferative response to Ang II through NO-dependent mechanisms. The attenuation of this inhibitory effect of leptin in spontaneous hypertension appears to be due to a reduced NO bioavailability in VSMCs.http://dx.doi.org/10.1155/2010/105489 |
| spellingShingle | Amaia Rodríguez Javier Gómez-Ambrosi Victoria Catalán Ana Fortuño Gema Frühbeck Leptin Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by Angiotensin II through Nitric Oxide-Dependent Mechanisms Mediators of Inflammation |
| title | Leptin Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by Angiotensin II through Nitric Oxide-Dependent Mechanisms |
| title_full | Leptin Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by Angiotensin II through Nitric Oxide-Dependent Mechanisms |
| title_fullStr | Leptin Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by Angiotensin II through Nitric Oxide-Dependent Mechanisms |
| title_full_unstemmed | Leptin Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by Angiotensin II through Nitric Oxide-Dependent Mechanisms |
| title_short | Leptin Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by Angiotensin II through Nitric Oxide-Dependent Mechanisms |
| title_sort | leptin inhibits the proliferation of vascular smooth muscle cells induced by angiotensin ii through nitric oxide dependent mechanisms |
| url | http://dx.doi.org/10.1155/2010/105489 |
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