Hemodynamics of early tubuloglomerular feedback resetting during reduced proximal reabsorption

Abstract

Carbonic anhydrase inhibition with benzolamide reduces proximal reabsorption and activates tubuloglomerular feedback (TGF). In rats, TGF activation for 30 to 60 minutes locally suppresses renin secretion and resets TGF rightward to accommodate increased late proximal flow. After 24 hours of TGF activation, there is upward resetting of GFR and increased activity of macula densa nitric oxide synthase I (NOS I). We studied renal hemodynamics during early TGF resetting with attention to the importance of renin suppression and NOS I activation. Left kidney blood flow (RBF, pulse Doppler) and glomerular filtration rate (GFR; inulin clearance or Fick method) were measured before and during benzolamide infusion (5 mg/kg bolus followed by 5 mg/kg/h IV) in Wistar rats concurrently receiving the converting enzyme inhibitor, enalaprilat (0.3 mg/kg/h IV) or NOS-I blocker S-methyl-thiocitrulline (SMTC; 2.7 mg/kg/h IV). Activating TGF initially reduced RBF and GFR in all groups as expected. During continuous benzolamide, RBF gradually increased toward baseline in control and enalaprilat-treated rats, but not in NOS I-blocked rats. After the initial decline, GFR did not change further during one hour of benzolamide in any group. During one hour of persistent TGF stimulation, RBF increases toward normal, but GFR does not. This requires an overall decrease in renal vascular resistance and a decrease in the ratio of efferent/afferent arteriolar resistance (RE/RA), implying a major decrease in RE. NOS I, but not angiotensin-converting enzyme (ACE), is required for RBF to increase during TGF resetting. Although the hemodynamic changes during TGF resetting resemble the response to blocking the renin-angiotensin system, these data fail to show that the increase in RBF during early TGF resetting is mediated by renin suppression.