Abstract-The kidney is a key controller of the long-term level of arterial pressure, in part through pressure-natriuresis.Although direct coupling of changes in renal arterial pressure to renal interstitial hydrostatic pressure (RIHP) and consequent sodium excretion is well established, few studies have characterized the moment-to-moment aspects of this process. These studies characterized the short-term hemodynamic component of pressure-natriuresis in vivo before and after autonomic nervous system and renin-angiotensin system inhibition. Changes in RIHP were determined over a range of renal arterial pressures in Wistar rats receiving no treatment, a ganglionic blocker (hexamethonium; 20 mg/kg per hour IV), or an angiotensin II type 1 receptor blocker (losartan; 10 mg/kg per hour IV). After a series of changes in renal arterial pressure, a delay of only Ϸ1 second was found for the onset of RIHP responses that was independent of the stimulus magnitude and neurohumoral manipulation; however, completion of the full RIHP response was within Ϸ15 seconds for renal arterial pressure changes of Յ30 mm Hg. The overall slope of the renal arterial pressure-RIHP relationship (0.09Ϯ0.01) was also not affected by autonomic nervous system and renin-angiotensin system inhibition despite decreasing renal arterial pressure (240% and 228%, respectively). Separate assessment of this relationship above and below the prevailing arterial pressure revealed that the pressor versus the depressor portion was blunted (PϽ0.001), a difference that was abolished after autonomic nervous system and renin-angiotensin system inhibition. The results suggest that spontaneous changes in arterial pressure are coupled to moment-to-moment changes in RIHP over a wide range of pressures, emphasizing a likely role for the dynamic component of the renal arterial pressure-RIHP relationship in the modulation of sodium excretion and, hence, arterial pressure. (Hypertension. 2010;56:650-657.)Key Words: kidney Ⅲ hydrostatic pressure Ⅲ arterial pressure Ⅲ natriuresis Ⅲ renin-angiotensin system Ⅲ autonomic nervous system T he kidney plays an important role in regulating blood volume and arterial pressure, in particular via a pressuredependent regulation of sodium and water balance, a process known as pressure-natriuresis. 1-4 Pressure-natriuresis acts through a final common pathway that directly couples renal arterial pressure (RAP) with renal interstitial hydrostatic pressure (RIHP), leading to changes in downstream sodium excretion (ie, increases in RIHP lead to enhanced sodium excretion). 4 -8 Given that pressure-natriuresis has been regarded as a "long-term" regulatory mechanism, it is not surprising that numerous studies have investigated the specific relationship between RAP and RIHP over a prolonged time course. Specifically, these studies induced graded step changes in RAP for Ն30 minutes and then recorded "steady-state" changes in RIHP and associated changes in sodium excretion. 9 -17 However, such assessments may not reflect true in vivo control of ar...