The Effects of Mineralocorticoid Receptor Antagonism on TRPV4 Mediated Vasodilation in the Aorta of Hypertensive Rats
Peel, Darren C.
MetadataShow full item record
Transient Receptor Potential Vanilloid 4 (TRPV4) channels are cation channels that have been shown to play a role in vasodilation. Understanding the vascular action of 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 regulating vascular tone, or degree of constriction of blood vessel. The activation of TRPV4 channels in particular has been shown to result in vasodilation. Similarly, mineralocorticoid receptors (MR) are known to affect vasodilation as well. However, the relationship between MR activation and TRPV4 channels is unknown. A major area of research is focused on a category of drugs known as MR antagonists. MR antagonists have beneficial effects on blood vessels of hypertensive patients. Canrenoic acid is a MR antagonist that is currently being investigated for its effects on MR mediated changes in vascular function. We hypothesized that MR antagonism with canrenoic acid would improve TRPV4 mediated dilation in the aorta of hypertensive rats. To test our hypothesis, we treated six-week-old male Spontaneously Hypertensive Stroke-Prone Rats (SHRSP) with canrenoic acid or 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). Our results were not as expected, as treatment with canrenoic acid did not directly improve vasodilation. However, our results do show that MR antagonism modulates TRPV4 function in hypertensive rats, although the mechanism has yet to be fully elucidated. The role of TRPV4 in vascular tone makes it a novel pharmacotherapeutic target for treatment of hypertension.