Abstract
Nitric oxide (NO) production impairment is involved in the onset and development of hypertension. Although NO production impairment in spontaneously hypertensive rat (SHR) has been reported in a variety of researches, the time course of this progressive procedure, as well as its relationship with asymmetric dimethylarginine (ADMA) and angiotensin II (Ang II), has not been quantified. The aim of this research is to establish a mechanism-based disease progression model to assess Ang II and ADMA's inhibition of NO production in SHR's disease progression with/without ramipril's intervention. SHR were randomly divided into three groups: one disease group (n = 8) and two treatment groups (n = 8 for each group): standard treatment group (receiving ramipril 2 mg/kg*day) and intensive treatment group (receiving ramipril 10 mg/kg*day). ADMA, Ang II, NO, and SBP were determined weekly. Intensive treatment with ramipril was found to have no further attenuation of plasma NO and ADMA than standard treatment beyond its significantly stronger antihypertensive effects. Four linked turnover models were developed to characterize the profiles of ADMA, Ang II, NO, and SBP during hypertensive disease progression with/without ramipril intervention. Our model described Ang II and ADMA's contribution to NO production impairment and their responses to ramipril treatment throughout the disease progression in SHR. Model simulations suggested that Ang II affected NO production mainly through inhibiting ADMA elimination rather than affecting nitric oxide synthase (NOS) directly.
Highlights
Hypertension is a serious chronic disease that causes mortality and morbidity worldwide
We aimed to offer a Abbreviations: ADMA, asymmetric dimethylarginine; Ang II, angiotensin II; DDAH, dimethylarginine dimethylaminohydrolase; GK rat, Goto-Kakizaki rat; NO, nitric oxide; NO synthase (NOS), nitric oxide synthase; RAS, renin-angiotensin system; ROS, reactive oxygen species; SBP, systolic blood pressure; SHR, spontaneously hypertensive rat
Higher dose of ramipril showed a stronger effect on plasma Ang II
Summary
Hypertension is a serious chronic disease that causes mortality and morbidity worldwide. Since DDAH provides the majority of ADMA removal (Baylis, 2012), inhibition of DDAH activity would lead to accumulation of ADMA in vivo, which subsequently affects the activity of NOS. Since these markers are closely related to each other and contribute greatly to hypertension, assessing the longitudinal time course of these markers might provide a better understanding of NO production impairment in hypertension disease progression of SHR
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
