Abstract
Because endothelial nitric oxide synthase (eNOS) has anti-inflammatory and anti-arteriosclerotic functions, it has been recognized as one of the key molecules essential for the homeostatic control of blood vessels other than relaxation of vascular tone. Here, we examined whether telmisartan modulates eNOS function through its pleiotropic effect. Administration of telmisartan to mice significantly increased the phosphorylation level of eNOS (Ser1177) in the aortic endothelium, but administration of valsartan had no effect. Similarly, telmisartan treatment of human umbilical vein endothelial cells significantly increased the phosphorylation levels of AMP-activated protein kinase (Thr172) and eNOS and the concentration of intracellular guanosine 3′,5′-cyclic monophosphate (cGMP). Furthermore, pretreatment with a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor suppressed the increased phosphorylation level of eNOS and intracellular cGMP concentration. These data show that telmisartan increases eNOS activity through Ser1177 phosphorylation in vascular endothelial cells mainly via p38 MAPK signaling.
Highlights
The renin-angiotensin system (RAS) is one of the most pivotal mechanisms that modulate blood pressure
Western blot analyses were performed to compare the phosphorylation levels of endothelial nitric oxide synthase (eNOS) Ser1177 and AMPKa Thr172 in human umbilical vein endothelial cells (HUVECs) stimulated by three different angiotensin II receptor blockers (ARBs), valsartan, irbesartan, and telmisartan, at 10 mM
We examined concentration-dependent differences in eNOS and AMPK phosphorylation levels induced by telmisartan
Summary
The renin-angiotensin system (RAS) is one of the most pivotal mechanisms that modulate blood pressure. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are frequently prescribed for the treatment of hypertension. They reduce the risk of renal dysfunction and the incidence of cardiovascular diseases [1,2,3,4,5]. The mechanism of the vascular protective effect of telmisartan is not fully understood. Both endothelial nitric oxide synthase (eNOS) and AMP-activated protein kinase (AMPK) have been suggested to play a role in the vascular endothelium to protect against the deteriorating effects of oxidative stress. It has been reported that AMPK is essential for angiogenesis in response to hypoxic stress [9]
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.
