Arterial smooth muscle cell PKD2 (TRPP1) channels contribute to angiotensin‐induced vascular remodeling

Abstract

Hypertension is associated with structural changes of resistance‐sized arteries, a process referred to as vascular remodeling, resulting in an increase in total peripheral resistance. One stimulus that exerts changes in arterial structure is an elevation in the vasoconstrictor angiotensin II (ang II), which mediates vascular smooth muscle cell growth, consequently resulting in vascular remodeling. Arterial smooth muscle cell PKD2 (TRPP1) channels, a member of the transient receptor potential (TRP) channel superfamily of ion channels, are upregulated in resistance‐sized arteries in ang II‐treated mice when compared to saline‐perfused controls. In addition, ang II‐treated conditional smooth muscle‐specific PKD2 knockout (PKD2sm−/−) mice demonstrate attenuated arterial wall remodeling and reduced blood pressure. An alteration in the expression and function of vascular smooth muscle cell ion channels also contributes to vascular remodeling through the promotion of cell proliferation. Here, we demonstrate that transient receptor potential canonical type 3 (TRPC3) and epidermal growth factor receptor (EGFR) channels, both indicated previously to contribute to ang II‐mediated vascular remodeling, are upregulated in mesenteric arteries isolated from ang II‐treated mice. During hypertension, TRPC3 channel function is also elevated, as demonstrated by application of the TRPC3 channel blocker pyrazole 3 (Pyr3) to pressurized 3rd and 4th order mesenteric arteries. Ang II‐treated PKD2sm−/− mice show reduced TRPC3 and EGFR expression, as well as decreased TRPC3 function when compared to ang II‐treated PKD2fl/fl controls. These data suggest that arterial smooth muscle cell PKD2 channels may contribute to TRPC3‐induced vascular remodeling in resistance‐sized mesenteric arteries.Support or Funding InformationAHA 16SDG27460007This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.