Sulagna Sensarma

The contribution of intrinsic and extrinsic controllers in renal function, such as elevated sensory or sympathetic renal activity, has been proposed to have an impact on long-term elevation in blood pressure relating to hypertension. Our lab has shown that the targeted denervation of the sensory renal nerves attenuates hypertension in some experimental animal models of hypertension, yet the mechanisms by which sensory renal nerves affect systemic blood pressure and renal vascular resistance have not been fully elucidated. We thus performed optogenetic experiments targeting sensory fibers in the mouse renal cortex to measure physiological outputs. A decrease in renal vascular resistance but no change in mean arterial pressure were measured in response to optogenetic stimulation, but additional experiments were required to confirm that these effects are mediated by sensory fibers themselves. Previously, we were able to characterize TRPV1+ fibers near renal glomeruli via the transgenic expression of tdTomato in TRPV1+ structures. However, extraneous tdTomato-expressing “cells” were imaged in addition to the TRPV1+ fibers, which also express Channelrhodopsin in our optogenetic mouse model. We co-labeled these “cells” with a CD45 antibody to confirm that they are not immune cells, which may interfere with our interpretation of our optogenetic results. Additionally, unilateral renal denervation was performed prior to optogenetic renal stimulation to test whether renal nerves are required for optogenetics-mediated decrease in renal vascular resistance. Our preliminary results confirm that the tdTomato+ “cells” are not immune cells and that unilateral renal denervation eliminates optogenetic effects, supporting that optogenetic stimulation is likely neurally mediated.