Direct Renin Inhibition Using Aliskiren Prevents Endothelial Dysfunction in Renal Arteries of Spontaneously Hypertensive Rats
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AbstractObjectives: Renovascular tone is an important determinant of systemic blood pressure. Hypertension is a significant clinical problem leading to cardiovascular comorbidities. The direct renin inhibitor aliskiren, is a novel anti-hypertensive agent with similar efficacy to angiotensin II receptor blockers. In this study, we tested the hypothesis that i) increased blood pressure in spontaneously hypertensive rats (SHRs) is associated with endothelial dysfunction in renal arteries, and ii) aliskiren exerts protective effects by reducing local oxidative stress.

Methods: Spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were randomly divided into aliskiren treatment group (10 mg/kg/day) or vehicle control group for eight weeks (n = 7). Bi-weekly monitoring of blood pressure was achieved using a tail-cuff method. Protein levels were determined by Western blotting.

Results: Endothelium-dependent dilatations to acetylcholine were significantly reduced in intralobal renal arteries from SHR as compared with those from age-matched WKY rats (Figure left). Aliskiren treatment significantly improved acetylcholine-induced dilatation in SHR renal arteries while vehicle treatment had no effect. By contrast, aliskiren treatment did not modify endothelium-dependent dilatations in WKY rat renal arteries. Bone morphogenetic protein 4, an upstream activator of vascular inflammation, and cyclooxygenase (COX)-2 expression, were increased in SHRs. These increases were prevented by aliskiren. COX-1 levels were similar in both WKY rats and SHRs in the presence or absence of aliskiren.

Conclusion: The direct renin inhibitor aliksiren exerts anti-hypertensive effects through suppression of the BMP4-COX2 axis.
All Author(s) ListGary TSE, Xiaoyu TIAN, Yu HUANG, Wing Tak WONG
Name of ConferenceThe 27th Scientific Meeting of the International Society of Hypertension
Start Date of Conference20/09/2018
End Date of Conference23/09/2018
Place of ConferenceBeijing
Country/Region of ConferenceChina
Proceedings TitleJournal of Hypertension
Volume Number36
Issue Numbere-Supplement 3
PagesAbstract no.: A2567
LanguagesEnglish-United States

Last updated on 2021-09-05 at 02:00