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Effect of Carotid Body Denervation on Systemic Endothelial Function in a Diabetic Animal Model
Marlene D Cabral1, Fátima O Martins1, Inês B Martins1
1iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal.
Insights
Resecting the carotid sinus nerve (CSN) in a type 2 diabetes model reversed hypertension and improved endothelial function. This suggests carotid body modulation may treat diabetes-related cardiovascular issues.
Area of Science:
- Cardiovascular Science
- Endocrinology
- Neuroscience
Background:
- Endothelial dysfunction is a key factor in cardiovascular diseases linked to diabetes and hypertension.
- Carotid body (CB) dysfunction contributes to metabolic disorders and hypertension (HT).
Purpose of the Study:
- To investigate if carotid sinus nerve (CSN) denervation improves systemic endothelial dysfunction in a type 2 diabetes mellitus (T2DM) animal model.
Main Methods:
- Wistar rats were fed a high-fat, high-sucrose diet for 25 weeks.
- CSN resection was performed on half the rats after 14 weeks.
- Evaluated insulin sensitivity, glucose tolerance, blood pressure, aortic function, nitric oxide (NO) levels, NOS isoforms, and PGF2αR.
Main Results:
- CSN resection reversed dysmetabolism and hypertension.
- Endothelial function in the aorta was restored post-CSN resection.
- NO levels decreased in plasma and aorta, with normalized iNOS levels in the aorta.
Conclusions:
- CSN denervation ameliorates endothelial dysfunction and hypertension in T2DM.
- Modulating CB activity offers a potential therapeutic strategy for HT and endothelial dysfunction associated with T2DM.
Abstract:
Endothelial dysfunction is an essential intermediary for development of cardiovascular diseases associated with diabetes and hypertension (HT). The carotid body (CB) dysfunction contributes to dysmetabolic states, and the resection of carotid sinus nerve (CSN) prevents and reverts dysmetabolism and HT. Herein, we investigated if CSN denervation ameliorates systemic endothelial dysfunction in an animal model of type 2 diabetes mellitus (T2DM).We used Wistar male rats submitted to HFHSu diet during 25 weeks and the correspondent age-matched controls fed with a standard diet. CSN resection was performed in half of the groups after 14 weeks of diet. In vivo insulin sensitivity, glucose tolerance and blood pressure, ex vivo aortic artery contraction and relaxation and nitric oxide (NO) levels in plasma and aorta, aorta nitric oxide synthase (NOS) isoforms, and PGF2αR levels were evaluated.We demonstrated that, alongside to dysmetabolism and HT reversion, CSN resection restores endothelial function in the aorta and decreases the NO levels in plasma and aorta at the same time that restores normal levels of iNOS in aorta without changing eNOS or PGF2αR levels.These results suggest that the modulation of CB activity can be important for the treatment of HT and endothelial dysfunction related with T2DM.
