Vascular Aldosterone Production at the Pre-Diabetic Stage of Young Otsuka Long-Evans Tokushima Fatty (OLETF) Rats, Compared with Long-Evans Tokushima Otsuka (LETO) Rats

Yoko Matsuzawa,Jun Saito,Masao Omura,Sachiko Suematsu,Tetsuo Nishikawa

doi:10.3390/molecules181215636

Yoko Matsuzawa, Jun Saito + Show 3 more

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https://doi.org/10.3390/molecules181215636

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Journal: Molecules	Publication Date: Dec 13, 2013
Citations: 26	License type: CC BY 4.0

Affiliation: Yokohama Rosai Hospital

Abstract

We examined the ability of aortic smooth muscle cells (AoSMC) prepared from spontaneously diabetic rats to produce aldosterone (Aldo) and the regulatory mechanism that controls their Aldo production. AoSMC of 6 week-old Long-Evans Tokushima Otsuka (LETO: the control group) and 6 week-old Otsuka Long-Evans Tokushima Fatty (OLETF: the type 2 diabetes group) rats were used in the present experiments. CYP11B2 (Aldo synthetase) mRNA expression was detected in both the LETO and OLETF AoSMC. Basal Aldo production was significantly greater (4–5 fold higher) in the OLETF AoSMC culture medium than in the LETO AoSMC culture medium. When AoSMC were co-incubated with high-density lipoproteins (HDL), supplying cholesterol as a substrate for steroidogenesis in rats, angiotensin II (AII) significantly increased greater Aldo production in the OLETF AoSMC than in the LETO AoSMC. The present data suggested that future onset of diabetic vascular dysfunction is partly caused by excess Aldo production by AoSMC in young OLETF rats. Concomitant stimulation by HDL and AII resulted in elevated Aldo production in the OLETF and the LETO AoSMC, and also demonstrated that AII-induced Aldo production is greatly enhanced by HDL in OLETF, rather than in LETO. In conclusion, our data clearly demonstrated that Aldo production in the OLETF AoSMC was significantly higher than in the LETO AoSMC, suggesting possible future onset of vascular dysfunction in diabetes, induced by local Aldo production in the AoSMC.

Highlights

Recent studies have shown that aldosterone is produced by various extra-adrenal tissues, including vascular smooth muscle cells [1,2,3], cardiac muscle cells [4], glomerular mesangial cells [5], the kidneys [6], and the brain [7]
Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats and control Long-Evans Tokushima Otsuka (LETO) rats.The mRNA of the indicated molecules was reverse-transcribed, and the resultant cDNA was amplified with RT-polymerase chain reaction (PCR)
Were incubated with 1.0 mM (Bu)2cAMP in the presence of 30 μM trilostane for 2 h, significantly greater pregnenolone production was observed in the OLETF aortic smooth muscle cells (AoSMC) culture medium than in the LETO

Summary

Introduction

Recent studies have shown that aldosterone is produced by various extra-adrenal tissues, including vascular smooth muscle cells [1,2,3], cardiac muscle cells [4], glomerular mesangial cells [5], the kidneys [6], and the brain [7]. An increasing body of evidence has underlined the importance of aldosterone in cardiovascular complications associated with metabolic syndrome, such as arterial remodeling and endothelial dysfunction, and MR blockade is increasingly being used as a form of evidence-based therapy for many forms of cardiovascular disease, including hypertension, heart failure, chronic kidney disease, and diabetes mellitus (DM) [9]. Otsuka Long-Evans Tokushima Fatty (OLETF) rats exhibit phenotypes that resemble those of humans with type 2 DM, for example, they display a chronic disease course involving mild obesity and possess multiple recessive genes for the induction of DM [12]. It is very interesting that vascular damage, including endothelial dysfunction, was reported to exist at 13 week-old in OLETF rats [13]

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