Enhanced tubuloglomerular feedback (TGF) responsiveness has been observed in several models of hypertension. This study was conducted to examine effects of increased renal perfusion pressure (RPP) on the magnitude of TGF-mediated afferent arteriolar (AA) vasoconstriction caused by increased distal nephron volume delivery. Diameters of juxtamedullary AA from kidneys of Sprague Dawley rats were measured in vitro at RPP of 100 and 160 mmHg using blood-perfused juxtamedullary nephron technique. To increase distal volume delivery, 10 mM acetazolamide (ACZ) was added to the blood perfusate. Thereafter, the papilla was cut to interrupt distal tubular flow. At 100 mmHg, AA diameter averaged 22.6±1.0 μm (n = 4) and decreased significantly by 6.9±1.0% with ACZ treatment. Papillectomy reversed the decrease in diameter. In a separate series (n= 6), elevation in RPP from 100 to 160 mmHg decreased AA diameter significantly by 21.4±2.0% to 19.1±1.2 μm. Subsequent administration of ACZ reduced the AA diameter by 18.0±2.9%. This diameter decrease was significantly greater than the AA response to ACZ observed at 100 mmHg and was similarly reversed by papillectomy. In a third series (n= 4), AA responses to ACZ were determined at 100 mmHg during 20 nM norepinephrine preconstricted AA to the same extent as achieved by increasing RPP to 160 mmHg. In these experiments, the decrease in diameter elicited by ACZ was 7.1±1.3% which was similar to that observed in control kidneys at 100 mmHg. These results suggest that increased perfusion pressure augments AA reactivity to increases in TGF-mediated vasoconstrictor signals.