Leptin inhibits the proliferation of vascular smooth muscle cells induced by angiotensin II through nitric oxide-dependent mechanisms.

Abstract

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 (3)H-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.

• Authors: Amaia Rodríguez, Javier Gómez-Ambrosi, Victoria Catalán, Ana Fortuño, Gema Frühbeck
• Journal: Mediators of inflammation (Mediators Inflamm) Vol. 2010 Pg. 105489 ( 2010) ISSN: 1466-1861 [Electronic] United States
• PMID: 20592755 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Leptin
• STAT3 Transcription Factor
• Angiotensin II
• Nitric Oxide
• Nitric Oxide Synthase
• Proto-Oncogene Proteins c-akt

Topics

• Angiotensin II (pharmacology)
• Animals
• Blood Glucose (metabolism)
• Cell Proliferation (drug effects)
• Leptin (blood, pharmacology)
• Male
• Muscle, Smooth, Vascular (cytology, drug effects)
• Myocytes, Smooth Muscle (cytology, drug effects, metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase (antagonists & inhibitors, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Inbred WKY
• Rats, Wistar
• Rats, Zucker
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (physiology)