Abstract
Several reports have shown that the periventricular region of the brain, including the paraventricular nucleus (PVN), is critical to sensing and responding to changes in plasma osmolality. Further studies also implicate the transient receptor potential ion channel, type V4 (TRPV4) channel in this homeostatic behavior. In previous work we have shown that TRPV4 ion channels couple to calcium-activated potassium channels in the PVN to decrease action potential firing frequency in response to hypotonicity. In the present study we investigated whether, similarly, intracerebroventricular (ICV) application of hypotonic solutions modulated cardiovascular parameters, and if so whether this was sensitive to a TRPV4 channel inhibitor. We found that ICV injection of 270 mOsmol artificial cerebrospinal fluid (ACSF) decreased mean blood pressure, but not heart rate, compared to naïve mice or mice injected with 300 mOsmol ACSF. This effect was abolished by treatment with the TRPV4 inhibitor RN1734. These data suggest that periventricular targets within the brain are capable of generating depressor action in response to TRPV4 ion channel activation. Potentially, in the future, the TRPV4 channel, or the TRPV4–KCa coupling mechanism, may serve as a therapeutic target for treatment of cardiovascular disease.
Highlights
Body fluid osmolality is usually regulated within an extremely narrow range (∼290–300 mOsmol; Bourque, 2008)
We began by confirming a previous report (Carreno et al, 2009) of TRPV4 ion channel expression within the paraventricular nucleus (PVN) using immunohistochemistry
In this study we identify a clear depressor action of euhydrated CD1 mice challenged with ICV hypotonic solution
Summary
Body fluid osmolality is usually regulated within an extremely narrow range (∼290–300 mOsmol; Bourque, 2008). This is largely maintained through regulation of renal function, but control areas exist within the central nervous system (CNS). Our particular focus has been on the PVN since this is an established autonomic control center exerting influence over heart rate (HR) and BP in response to a number of homeostatic challenges including temperature (Cham and Badoer, 2008), day–night cycle (Feetham and Barrett-Jolley, 2014), volume load (Lovick et al, 1993), and osmolarity (Stocker et al, 2004a)
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