Abstract Body: Renal sensory nerves innervate the pelvic wall, tubules, glomeruli and vasculature and respond to renal ischemia, altered pelvic pressure and various chemokines. Activation of these afferent nerves elevates sympathetic nerve activity (SNA) and arterial blood pressure (ABP). The rostral ventrolateral medulla (RVLM) and hypothalamic paraventricular nucleus (PVH) receive renal afferent input, and mono- or poly-synaptically innervate sympathetic preganglionic neurons. The present study tested the extent by which RVLM or PVH neurons mediate hemodynamic responses to activation of renal afferent nerves. Inactin-anesthetized, male Sprague-Dawley rats (8-12 weeks age, n=4 per group) received an infusion (50uL per 15s) of bradykinin (0.1-10uM) or capsaicin (0.1-10uM) through a catheter advanced into the right renal artery via the adrenal artery. Contralateral renal SNA and ABP responses were measured after bilateral microinjection of artificial cerebrospinal fluid (aCSF, 50nL) or the GABA receptor agonist muscimol (5mM, 50nL) to pharmacologically inhibit the RVLM or PVH. Inhibition of the PVH eliminated sympathoexcitatory responses to intrarenal infusion of bradykinin including renal SNA (aCSF vs muscimol: 1uM, 155±13 vs 114±4%; 10uM, 175±18 vs 134±8%) and ABP (aCSF vs muscimol: 1uM, 7±2 vs 2±2mmHg; 10uM, 14±3 vs 5±1mmHg). PVH inhibition also attenuated responses to intrarenal infusion of capsaicin including renal SNA (aCSF vs muscimol: 1uM, 167±13 vs 143±9%; 10uM, 194±115 vs 160±6%) and ABP (aCSF vs muscimol: 1uM, 8±2 vs 2±3mmHg; 10uM, 12±3 vs 3±3mmHg). In marked contrast, inhibition of the RVLM did not attenuate, but at times enhanced, sympathoexcitatory responses to intrarenal infusion of bradykinin including renal SNA (aCSF vs muscimol: 1uM, 135±5 vs 220±83%; 10uM: 163±19 vs 347±122%) and ABP (aCSF vs muscimol: 1uM, 10±1 vs 13±5mmHg; 10uM: 17±2 vs 22±7mmHg). Similarly, inhibition of the RVLM did not attenuate responses to intrarenal infusion of capsaicin including renal SNA (aCSF vs muscimol: 1uM, 143±7 vs 300±71%; 10uM, 178±26 vs 453±115%) and ABP (aCSF vs muscimol: 1uM, 7±1 vs 16±2mmHg; 10uM, 13±3 vs 30±7mmHg). These findings suggest sympathoexcitatory responses elicited by intrarenal chemokines are mediated by PVH neurons independent of the RVLM. Supported by: NIH HL152680, HL163906, DK135541