| First Author | Huang Y | Year | 2013 |
| Journal | Hypertension | Volume | 62 |
| Issue | 3 | Pages | 634-40 |
| PubMed ID | 23918749 | Mgi Jnum | J:265979 |
| Mgi Id | MGI:6201795 | Doi | 10.1161/HYPERTENSIONAHA.111.00160 |
| Citation | Huang Y, et al. (2013) Hypoxia-inducible factor-1alpha in vascular smooth muscle regulates blood pressure homeostasis through a peroxisome proliferator-activated receptor-gamma-angiotensin II receptor type 1 axis. Hypertension 62(3):634-40 |
| abstractText | 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-1alpha (HIF-1alpha) in controlling blood pressure homeostasis. The lack of HIF-1alpha 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-1alpha, through peroxisome proliferator-activated receptor-gamma, 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-1alpha-KO mice. These data revealed a determinant role of a smooth muscle HIF-1alpha/peroxisome proliferator-activated receptor-gamma/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. |
