Abstract-A direct relationship between renal arterial pressure (RAP) and renal interstitial hydrostatic pressure (RIHP) has been shown under conditions of efficient renal blood flow autoregulation. Experiments were performed in six anesthetized dogs to evaluate whether these RIHP responses to changes in RAP were modified during nitric oxide (NO) inhibition with nitro-L-arginine (NLA) or after administration of NO donor agents. A microtip catheter transducer was placed underneath the renal capsule to measure RIHP. Stepwise reductions in RAP (140 to 80 mm Hg) during control conditions resulted in decreases in RIHP from its basal value of 4.7Ϯ1.1 mm Hg with a slope of 0.04Ϯ0.026 mm Hg ⅐ mm Hg Ϫ1 along with decreases in urinary nitrate/nitrite excretion rate (U NOx V). Renal cortical and medullary blood flows, measured by laser-Doppler flowmetry, exhibited high autoregulatory efficiency over this RAP range. The changes in RIHP during alterations in RAP were positively correlated (rϭ0.743; PϽ0.001) with the changes in U NOx V but not with cortical or medullary blood flow. NLA infusion decreased RIHP to 1.9Ϯ0.5 mm Hg and also reduced U NOx V from 1.8Ϯ0.2 to 0.9Ϯ0.01 nmol ⅐ min Ϫ1 ⅐ g Ϫ1 . Infusion of NO donors restored RIHP (4.3Ϯ0.9 mm Hg) andDuring NLA infusion, the RIHP responses to reductions in RAP were markedly attenuated and were not restored even during constant-rate infusion of NO donors. The results suggest that changes in RIHP in response to alterations in RAP are associated with changes in intrarenal NO, suggesting a direct effect of NO to regulate RIHP. Key Words: renal regional blood flow Ⅲ laser-Doppler flowmetry Ⅲ nitrate/nitrite excretion P revious studies in dogs and rats have shown that changes in renal arterial pressure (RAP), within the autoregulatory range, are associated with changes in renal interstitial hydrostatic pressure (RIHP), and it has been suggested that these changes in RIHP contribute to the control of tubular reabsorptive function via alterations in the renal interstitial environment. [1][2][3][4][5] The mechanism responsible for RAP-induced changes in RIHP has remained difficult to explain, because renal blood flow (RBF) and peritubular capillary pressure are efficiently autoregulated during alterations in RAP over a wide range. 6 -8 Findings in volume-expanded rats that the renal medullary blood flow (MBF) is more sensitive to changes in RAP than the cortical blood flow (CBF) 9 have led to the suggestion that impaired autoregulatory efficiency of MBF may be linked to the changes in RIHP. 1,10 However, direct associations between changes in RIHP and changes in regional blood flows in the kidney during alterations in RAP have not been established. In addition, studies in dogs as well as in euvolumic rats have failed to demonstrate reduced autoregulatory efficiency of MBF. 6,9,11,12 Inhibition of nitric oxide (NO) synthesis in rats was shown to decrease RIHP and attenuate RIHP responses to changes in renal perfusion pressure. 3 Moreover, selective inhibition of NO in the rat renal med...