Analysis of the tubuloglomerular feedback mechanism in renal autoregulation

Along the juxtaglomerular segment of the afferent arteriole the luminal pressure p approaches the glomerular capillary pressure of 55-60 mmHg. At such low luminal pressures the myogenic mechanism contracts only if extravascular pressure p(ex) is subatmospheric. According to Poiseuille's formula complete autoregulation requires that blood flow is F=5Kr(0)(4)/Deltax at arterial pressures exceeding 65 mmHg; r(0) is the radius of the relaxed segment at transmural pressure p - p(ex) < or =60 mmHg, where p(ex) is the extravascular pressure; Deltax is the length of the main preglomerular segment, 10 times longer than the juxtaglomerular segment. Consistent with in vitro studies a myogenic mechanism may reduce the relaxed juxtaglomerular radius r(jx)=0.7r(0) by 40% at a transmural pressure of 140 mmHg. Fifty and 60% reductions are also considered. Integration of Poiseuille's formula shows that complete autoregulation of preglomerular blood flow requires negative extravascular pressures p(ex)= -90 to -55 mmHg dependent on contractile force. Negative pressure of this magnitude is generated by effective hyperosmolality <5 mOsm across the membrane separating cleft from pole cushion. Negative pressure stays constant at arterial pressures exceeding 90-110 mmHg, implying constant tubuloglomerular feedback, but approaches atmospheric pressure at lower arterial pressure, suggesting maintenance of blood flow by reduction in the glomerular filtration rate; a rise in macula densa concentrations [NaCl](md) by 0.15 mM or [NaHCO(3)](md) by 2 mM raises extravascular pressure towards atmospheric levels by approximately 40 mmHg. A 40-mmHg rise in interstitial pressure exerts the same effect. Loop diuretics nullify osmotic force and dilate juxtaglomerular and main segments by raising juxtaglomerular extravascular pressure towards atmospheric levels.