Chronic hyperhomocysteinemia impairs vascular function in ovariectomized rat carotid arteries
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Published on: August 13, 2019
Andréa Carla Celotto1, Sandra Y Fukada, Francisco R M Laurindo
1Laboratory of Pharmacology, Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences, University of São Paulo (USP), Avenida do Café 3900, Ribeirão Preto, SP, CEP 14040-903, Brazil. acarla_c@yahoo.com
Insights
Hyperhomocysteinemia (HHcy) impairs carotid artery function in female rats by affecting nitric oxide pathways. Inhibiting nitric oxide synthase restored normal vascular responses, highlighting its role in HHcy-induced vascular dysfunction.
Area of Science:
- Vascular Biology
- Endocrinology
- Pharmacology
Background:
- Homocysteine is a known risk factor for cardiovascular diseases.
- Hyperhomocysteinemia (HHcy) is linked to vascular dysfunction.
- Ovariectomized female rats provide a model to study vascular changes.
Purpose of the Study:
- To investigate the impact of HHcy on carotid artery reactivity in ovariectomized female rats.
- To explore the role of nitric oxide (NO) in HHcy-induced vascular dysfunction.
Main Methods:
- Rats were treated with DL-Hcy thiolactone to induce HHcy.
- Carotid artery segments were isolated and subjected to contractile and relaxation studies.
- Expression of iNOS, eNOS, and nitrotyrosine was analyzed.
- Nitric oxide synthase (NOS) inhibitors were used to assess NO involvement.
Main Results:
- HHcy reduced phenylephrine-induced contraction but did not affect KCl-induced contraction or relaxations to SNP/ACh.
- Elevated iNOS, eNOS, and nitrotyrosine were observed in HHcy-treated arteries.
- NOS inhibition (L-NAME, 1,400 W, L-NNA) restored vasoconstriction in HHcy-treated arteries.
Conclusions:
- Severe HHcy acutely decreases endothelium-independent contractile responses in carotid arteries.
- Nitric oxide plays a significant role in HHcy-derived vascular dysfunction.
- Targeting NO pathways may offer therapeutic potential for HHcy-related vascular issues.
Abstract:
Homocysteine is an independent risk factor for coronary heart disease, as well as for cerebrovascular and peripheral vascular diseases. The purpose of this study was to investigate the effects of hyperhomocysteinemia (HHcy) on vascular reactivity within carotid artery segments isolated from ovariectomized female rats. Treatment with DL-Hcy thiolactone (1 g/kg body weight per day) reduced the phenylephrine-induced contraction of denuded rings. However, the treatment did not alter KCl-induced contractions, or relaxations induced by sodium nitroprusside or acetylcholine. We report elevated expressions of iNOS, eNOS, and nitrotyrosine in homocysteine-treated rat artery sections. Moreover, the inhibition of NOS by L-NAME, 1,400 W, or L-NNA restored phenylephrine-induced vasoconstriction in carotid artery segments from Hcy-treated rats. In conclusion, our findings show that severe HHCy can promote an acute decrease in the endothelium-independent contractile responses of carotid arteries to adrenergic agonists. This effect was restored by nitric oxide synthase inhibitors, which further supports the involvement of nitric oxide in HHcy-derived vascular dysfunction.
