Abstract 15268: Role of Transient Receptor Potential Vanilloid 4 Channels in the Periventricular Nucleus (PVN) Neurons on the Regulation of Blood Pressure in Dahl R versus Dahl S Rats
Transient receptor potential vanilloid 4 (TRPV4) channels are expressed in brain neurons involved in systemic osmoregulation; and intravenous administration of TRPV4 channel antagonists elevates arterial pressure in peripheral. Here, we examined the role of TRPV4 in the regulation of blood pressure and neuronal activity in the PVN of Dahl S and Dahl R rats. Microinjection of TRPV4 antagonists, HC067047 (10 uM, in 50 nl) or ruthenium red (10 uM, in 50 nl), into the PVN significantly increased mean arterial pressure (MAP) and heart rate (HR) in both Dahl R and Dahl S rats on either high salt or normal diet. However, the pressor and tachycardia effects of TRPV4 channel blockers were significantly impaired in Dahl S rats on high salt diet as compared with other groups of rats. In contrast, PVN microinjection of the TRPV4 agonist, GSK1016790A (100 nM, in 50 nl), markedly reduced MAP and HR in all groups of rats. The depressor and bradycardia effects induced by TRPV4 stimulation were significantly reduced in the high salt-treated Dahl S rats as compared with other groups of rats. Immunohistochemistry using specific TRPV4 and NeuN antibodies demonstrated TRPV4 was located in PVN neurons in rat brain sections. Thus, we next examined the actions of TRPV4 channel agonists and antagonists on neuronal activity in neurons cultured from the hypothalamus of neonatal Dahl R rats using patch clamp recording in current clamp mode. Superfusion of neurons with HC067047 (1 uM) or ruthenium red (10 uM) significantly increased neuronal firing rate from 0.50±0.04 Hz to 0.94±0.08 Hz and from 0.52±0.04 Hz to 0.92±0.09 Hz respectively.. In contrast, superfusion of neurons with GSK1016790A (100 nM) dramatically decreased neuronal firing rate from 0.63±0.03 Hz to 0.32±0.02 (n=9, P<0.05). Taken together, the results demonstrate that inhibition of TRPV4 channels in the PVN increases neuronal activity and arterial pressure. Impaired TRPV4 channel activity in the PVN may be involved in the development of hypertension in Dahl S rats on a high salt diet.
- © 2013 by American Heart Association, Inc.