Hypoxia-Inducible Factor-1α in Vascular Smooth Muscle Regulates Blood Pressure Homeostasis Through a Peroxisome Proliferator–Activated Receptor-γ–Angiotensin II Receptor Type 1 Axis

Content Provider	Scilit
Author	Huang, Yan Lorenzo, Annarita Di Jiang, Weidong Cantalupo, Anna Sessa, William C. Giordano, Frank J.
Copyright Year	2013
Description	Journal: Hypertension Hypertension is a major worldwide health issue for which only a small proportion of cases have a known mechanistic pathogenesis. Of the defined causes, none have been directly linked to heightened vasoconstrictor responsiveness, despite the fact that vasomotor tone in resistance vessels is a fundamental determinant of blood pressure. Here, we reported a previously undescribed role for smooth muscle hypoxia-inducible factor-1α (HIF-1α) in controlling blood pressure homeostasis. The lack of HIF-1α in smooth muscle caused hypertension in vivo and hyperresponsiveness of resistance vessels to angiotensin II stimulation ex vivo. These data correlated with an increased expression of angiotensin II receptor type I in the vasculature. Specifically, we show that HIF-1α, through peroxisome proliferator–activated receptor-γ, reciprocally defined angiotensin II receptor type I levels in the vessel wall. Indeed, pharmacological blockade of angiotensin II receptor type I by telmisartan abolished the hypertensive phenotype in smooth muscle cell-HIF-1α-KO mice. These data revealed a determinant role of a smooth muscle HIF-1α/peroxisome proliferator–activated receptor-γ/angiotensin II receptor type I axis in controlling vasomotor responsiveness and highlighted an important pathway, the alterations of which may be critical in a variety of hypertensive-based clinical settings.
Related Links	http://europepmc.org/articles/pmc4354705?pdf=render https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354705/pdf https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.111.00160
Ending Page	640
Page Count	7
Starting Page	634
ISSN	0194911X
e-ISSN	15244563
DOI	10.1161/hypertensionaha.111.00160
Journal	Hypertension
Issue Number	3
Volume Number	62
Language	English
Publisher	Ovid Technologies (Wolters Kluwer Health)
Publisher Date	2013-09-01
Access Restriction	Open
Subject Keyword	Journal: Hypertension Peripheral Vascular Disease
Content Type	Text
Resource Type	Article
Subject	Internal Medicine