The Effects of Mineralocorticoid Receptor Antagonism on TRPV4 Mediated Vasodilation in the Aorta of Hypertensive Rats
Peel, Darren C.
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Understanding the vascular action of transient receptor potential (TRP) vanilliod 4 (TRPV4) channels is imperative to the development of novel and effective therapeutic treatments for hypertension. TRP channels are potential therapeutic targets due to their role in vascular tone. The activation of TRPV4 channels in particular have been shown to result in vasodilation. Additional areas of research have elucidated the effects of mineralocorticoid receptors (MR) in hypertension. However the mechanism of MR activation and its relation to TRPV4 are still unknown. A major area of research is focused on a category known as MR antagonists, known to be anti-hypertensive agents. Canrenoic acid is a MR antagonist that is currently being researched for its role in vascular tone. We hypothesized that canrenoic acid will prevent the impairment of TRPV4 mediated dilation in the aorta of hypertensive rats. To test our hypothesis, we treated six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) with canrenoic acid or a control vehicle (water) for six weeks. Following treatment, aortic vasodilation was assessed using wire myography in the presence of TRPV4 agonist (GSK1016790A) or TRPV4 antagonist (GSK2193874). The results show no significant difference in vasodilation between canrenoic acid treated rats and control for acetylcholine and GSK1016790A. However, our results show an increase vasodilation when incubated with GSK2193874 in canrenoic acid treated groups. Expression of TRPV4 in smooth muscle and endothelial cells of the cardiovascular system along with its role in vascular tone make it a novel pharmacotherapeutic target for treatment of hypertension.