Inflammatory Renin-Angiotensin System Disruption Attenuates Sensory Hyperinnervation and Mechanical Hypersensitivity in a Rat Model of Provoked Vestibulodynia

The RAS (renin–angiotensin system) is classically involved in BP (blood pressure) regulation and water–electrolyte balance, and in the central nervous system it has been mostly associated with homoeostatic processes, such as thirst, hormone secretion and thermoregulation. Epilepsies are chronic neurological disorders characterized by recurrent epileptic seizures that affect 1–3% of the world's population, and the most commonly used anticonvulsants are described to be effective in approx. 70% of the population with this neurological alteration. Using a rat model of epilepsy, we found that components of the RAS, namely ACE (angiotensin-converting enzyme) and the AT1 receptor (angiotensin II type 1 receptor) are up-regulated in the brain (2.6- and 8.2-fold respectively) following repetitive seizures. Subsequently, epileptic animals were treated with clinically used doses of enalapril, an ACE inhibitor, and losartan, an AT1 receptor blocker, leading to a significant decrease in seizure severities. These results suggest that centrally acting drugs that target the RAS deserve further investigation as possible anticonvulsant agents and may represent an additional strategy in the management of epileptic patients.

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The renin-angiotensin system in the synovium promotes periarticular osteopenia in a rat model of collagen-induced arthritis

International Immunopharmacology ◽

10.1016/j.intimp.2018.11.001 ◽

2018 ◽

Vol 65 ◽

pp. 550-558 ◽

Cited By ~ 11

Author(s):

Yingzhen Wang ◽

Jianqiang Kou ◽

Haining Zhang ◽

Changyao Wang ◽

Haiyan Li ◽

...

Keyword(s):

Rat Model ◽

Renin Angiotensin System ◽

Collagen Induced Arthritis ◽

Angiotensin System ◽

Renin Angiotensin

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Activation of the GLP-1 Receptor by Liraglutide Increases ACE2 Expression, Reversing Right Ventricle Hypertrophy, and Improving the Production of SP-A and SP-B in the Lungs of Type 1 Diabetes Rats

Endocrinology ◽

10.1210/en.2014-1685 ◽

2015 ◽

Vol 156 (10) ◽

pp. 3559-3569 ◽

Cited By ~ 64

Author(s):

Marina Romaní-Pérez ◽

Verónica Outeiriño-Iglesias ◽

Christian M. Moya ◽

Pilar Santisteban ◽

Lucas C. González-Matías ◽

...

Keyword(s):

Type 1 Diabetes ◽

Right Ventricle ◽

Rat Model ◽

Renin Angiotensin System ◽

Surfactant Protein ◽

Angiotensin System ◽

Renin Angiotensin ◽

Ventricle Hypertrophy ◽

Right Ventricle Hypertrophy

Diabetes alters microvascular function in the vascular beds of organs, including the lungs. Cardiovascular complications of pulmonary vascular affectation may be a consequence of the overactivation of the vasoconstrictive and proliferative components of the renin-angiotensin system. We previously reported that pulmonary physiology and surfactant production is improved by the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide (LIR) in a rat model of lung hypoplasia. Because we hypothesized that streptozotocin-induced diabetes rats would show deficiencies in lung function, including surfactant proteins, and develop an imbalance of the renin-angiotensin system in the lungs. This effect would in turn be prevented by long-acting agonists of the GLP-1R, such as LIR. The induction of diabetes reduced the surfactant protein A and B in the lungs and caused the vasoconstrictor component of the renin-angiotensin system to predominate, which in turn increased angiotensin II levels, and ultimately being associated with right ventricle hypertrophy. LIR restored surfactant protein levels and reversed the imbalance in the renin-angiotensin system in this type 1 diabetes mellitus rat model. Moreover, LIR provoked a strong increase in angiotensin-converting enzyme 2 expression in the lungs of both diabetic and control rats, and in the circulating angiotensin(1–7) in diabetic animals. These effects prompted complete reversion of right ventricle hypertrophy. The consequences of LIR administration were independent of glycemic control and of glucocorticoids, and they involved NK2 homeobox 1 signaling. This study demonstrates by first time that GLP-1R agonists, such as LIR, might improve the cardiopulmonary complications associated with diabetes.

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