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Title: Thromboxane receptors in smooth muscle promote hypertension, vascular remodeling, and sudden death
Authors: Sparks, M.A.
Makhanova, N.A.
Griffiths, R.C.
Snouwaert, J.N.
Koller, B.H.
Coffman, T.M. 
Keywords: Ang II
muscle, smooth
Issue Date: Jan-2013
Citation: Sparks, M.A., Makhanova, N.A., Griffiths, R.C., Snouwaert, J.N., Koller, B.H., Coffman, T.M. (2013-01). Thromboxane receptors in smooth muscle promote hypertension, vascular remodeling, and sudden death. Hypertension 61 (1) : 166-173. ScholarBank@NUS Repository.
Abstract: The prostanoid thromboxane A2 has been implicated to contribute to the pathogenesis of many cardiovascular diseases, including hypertension. To study the role of vascular thromboxane-prostanoid (TP) receptors in blood pressure regulation, we generated mice with cell-specific deletion of TP receptors in smooth muscle using Cre/Loxp technology. We crossed the KISM22α-Cre transgenic mouse line expressing Cre recombinase in smooth muscle cells with a mouse line bearing a conditional allele of the Tbxa2r gene (Tpflox). In KISM22α-Cre+Tpflox/flox (TP-SMKO) mice, TP receptors were efficiently deleted from vascular smooth muscle cells. In TP-SMKOs, acute vasoconstrictor responses to the TP agonist U46619 were attenuated to a similar extent in both the peripheral and renal circulations. Yet, acute vascular responses to angiotensin II were unaffected at baseline and after chronic angiotensin II administration. Infusion of high-dose U46619 caused circulatory collapse and death in a majority of control mice but had negligible hemodynamic effects in TP-SMKOs, which were completely protected from U46619-induced sudden death. Baseline blood pressures were normal in TP-SMKOs. However, the absence of TP receptors in vascular smooth muscle cells was associated with significant attenuation of angiotensin II-induced hypertension and diminished vascular remodeling. This was also associated with reduced urinary thromboxane production after chronic angiotensin II. Thus, TP receptors in vascular smooth muscle cells play a major role in mediating the actions of thromboxane A2 in TP agonist-induced shock, hypertension, and vascular remodeling of the aorta. © 2012 American Heart Association, Inc.
Source Title: Hypertension
ISSN: 0194911X
DOI: 10.1161/HYPERTENSIONAHA.112.193250
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