Physical Training vs. Perindopril Treatment on Arterial Stiffening of Spontaneously Hypertensive Rats: A Proteomic Analysis and Possible Mechanisms

Abstract

(1) Background: Arterial stiffness is an important predictor of cardiovascular events. Perindopril and physical exercise are important in controlling hypertension and arterial stiffness, but the mechanisms are unclear. (2) Methods: Thirty-two spontaneously hypertensive rats (SHR) were evaluated for eight weeks: SHRC (sedentary); SHRP (sedentary treated with perindopril—3 mg/kg) and SHRT (trained). Pulse wave velocity (PWV) analysis was performed, and the aorta was collected for proteomic analysis. (3) Results: Both treatments determined a similar reduction in PWV (−33% for SHRP and −23% for SHRT) vs. SHRC, as well as in BP. Among the altered proteins, the proteomic analysis identified an upregulation of the EH domain-containing 2 (EHD2) protein in the SHRP group, required for nitric oxide-dependent vessel relaxation. The SHRT group showed downregulation of collagen-1 (COL1). Accordingly, SHRP showed an increase (+69%) in the e-NOS protein level and SHRT showed a lower COL1 protein level (−46%) compared with SHRC. (4) Conclusions: Both perindopril and aerobic training reduced arterial stiffness in SHR; however, the results suggest that the mechanisms can be distinct. While treatment with perindopril increased EHD2, a protein involved in vessel relaxation, aerobic training decreased COL1 protein level, an important protein of the extracellular matrix (ECM) that normally enhances vessel rigidity.

From Living in Saltwater to a Scarcity of Salt and Water, and Then an Overabundance of Salt—The Biological Roller Coaster to Which the Renin–Angiotensin System Has Had to Adapt: An Editorial

“…The reduced aortic stiffness they observed seems to be connected to the elevated expression of the Ehd2 (EH domain-containing) protein, a component involved in the endothelial nitric oxide synthase (eNOS)-nitric oxide (NO) endothelial vasodilatory pathway. They succeeded in proving that the rigidityreducing effect of chronic exercise has a different mechanism [7]. The extremely complex nature of the renin-angiotensin system (RAS) is shown by another paper in this Special Issue.…”

“…Three papers which have been published in this Special Issue deal with such pleiotropic functions of the renin-angiotensin system (RAS). In an excellent study by Miotto et al [7] from the State University of Sao Paulo, Brazil, the aortic wall of perindopril-treated spontaneously hypertensive rats (SHR) was analyzed. Using the best available high throughput proteomic methods, they found that chronic treatment with the angiotensin converting enzyme (ACE) inhibitor perindopril in the artic wall altered 38 subcategories of cellular protein components, among them "supramolecular polymer", "heterotrimeric G protein complex", "actin cytoskeleton", "supramolecular fiber", "intermediate filament", "membrane raft" and "oxidoreductase" complexes.…”