Inhibition Of Tubuloglomerular Feedback Research Articles

Adenosine alters glomerular filtration control by angiotensin II.

This study was designed to test the hypothesis that high renal levels of adenosine (ADO) may alter glomerular filtration rate (GFR) control by angiotensin II (ANG II). In normal kidneys, ANG II infusion (20 ng X kg-1 X min-1 iv) decreased renal blood flow (RBF) to 61 +/- 3% of control, increased filtration fraction (FF) to 173 +/- 21% of control, and did not change GFR significantly. During intrarenal ADO infusion at a rate of 1.0 mumol/min, ANG II (20 ng X kg-1 X min-1 iv) decreased RBF and GFR to 61 +/- 5 and 64 +/- 6% of control, respectively. After blocking changes in tubuloglomerular feedback by occluding the ureter during mannitol diuresis, ANG II increased stop-flow pressure and postglomerular resistance (RPG) markedly but did not alter preglomerular resistance (RA), suggesting that the direct actions of circulating ANG II are confined primarily to efferent arterioles in the absence of changes in tubuloglomerular feedback. However, during intrarenal ADO infusion and inhibition of tubuloglomerular feedback, ANG II decreased stop-flow ureteral pressure and raised RA and RPG to 213 +/- 27 and 155 +/- 7% of control, respectively, while decreasing RBF to 59 +/- 5% of control. These observations suggest that ADO markedly alters the control of GFR by ANG II, possibly by causing ANG II to constrict preglomerular vessels, an effect that is not apparent in most physiological conditions but which could play a role in lowering GFR when renal ADO and ANG II levels are both elevated, as in severe renal ischemia.

Tubuloglomerular feedback and SNGFR autoregulation in the rat.

Experimental and simulation studies were undertaken to examine what influence the state of filtration dynamics has on single nephron glomerular filtration rate (SNGFR) autoregulation, to verify the presence of partial autoregulation during tubuloglomerular feedback (TGF) inhibition, and to determine whether small changes in tubular reabsorption could enhance the ability of TGF to regulate SNGFR during autoregulation. The experimental studies in hydropenic rats revealed partial autoregulation of glomerular capillary pressure (using the stop-flow method) and SNGFR during TGF inhibition and complete SNGFR autoregulation with functional TGF. A small significant decrease in fractional volume reabsorption was observed in the distal measurements with increased arterial pressure. Results from a mathematical model of glomerular filtration suggest that SNGFR is inherently more sensitive to changes in arterial pressure in animals exhibiting filtration pressure equilibrium rather than filtration pressure disequilibrium. These data and the simulation results provide additional support for the existence of a TGF-independent autoregulatory mechanism that appears to be an intrinsic property of the preglomerular vasculature. Finally, analysis of autoregulation with a simple control-system model suggests that small changes in proximal tubule or loop of Henle volume reabsorption can provide some or all of the stimulus for TGF activation, thereby significantly increasing the ability of TGF to stabilize SNGFR in response to a rise in arterial pressure.

Renal hemodynamic actions of angiotensin II: interaction with tubuloglomerular feedback.

The present study was designed to investigate the importance of interactions between angiotensin II (ANG II) and other intrinsic control mechanisms, including tubuloglomerular feedback (TGF), in controlling renal hemodynamics. When endogenous ANG II formation was blocked by SQ 14225 infusion and changes in myogenic activity were minimized by servo controlling renal arterial pressure, ANG II infusion (20 ng . kg-1 . min-1 iv) did not change glomerular filtration rate but decreased renal blood flow (RBF) from 286 +/- 36 to 179 +/- 31 ml/min due to increases in calculated preglomerular (54%) and efferent (100%) arteriolar resistances. After inhibition of TGF by occluding the ureter during mannitol diuresis, ANG II infusion (20 ng . kg-1 . min-1) decreased RBF from 229 +/- 25 to 151 +/- 19 ml/min while increasing glomerular hydrostatic pressure (calculated from ureteral stop-flow pressure and plasma colloid osmotic pressure) from 56.7 +/- 2.5 to 62.3 +/- 2.2 mmHg. Postglomerular resistance increased to 173 +/- 17% of control, but preglomerular resistance did not change significantly during ANG II infusion after inhibition of TGF. These data suggest that the direct renal vasoconstrictor action of ANG II is confined mainly to postglomerular vessels and that changes in preglomerular resistance that occur when ANG II levels are inappropriately elevated in normal animals are caused by other intrinsic control mechanisms, such as TGF.

Feedback mediation of SNGFR autoregulation in hydropenic and DOCA- and salt-loaded rats.

Tubuloglomerular feedback (TGF) mediation of autoregulation was investigated by measuring the response of single nephron glomerular filtration rate (SNGFR) to changes in arterial pressure (AP) following acute or chronic TGF inhibition. In hydropenic rats with intact TGF, distal SNGFR was 25.0 +/- 1.2 (SE) and 23.9 +/- 1.4 nl/min at AP of 111 and 135 mmHg, respectively. In the same 20 nephrons during proximal tubular microinfusion of furosemide, distal SNGFR was 23.6 +/- 1.4 (n = 16) and 29.7 +/- 1.4 nl/min (n = 20) (P less than 0.001, n = 16) at 112 and 133 mmHg. When determined proximally, SNGFR was 25.6 +/- 1.0 and 29.5 +/- 0.9 nl/min (P less than 0.001, n = 31) at 112 and 157 mmHg; kidney GFR increased similarly. These data and the predictions of a GFR model were then used to estimate autoregulatory efficiency. This analysis indicated that partial autoregulation occurred during TGF inhibition. Therefore, TGF is an essential, but probably not the only, mechanism mediating SNGFR autoregulation.