Glomerular mesangium as an effector locus for the tubuloglomerular feedback system and renal sympathetic innervation

To define the effector loci for the tubuloglomerular feedback system, the determinants of the single-nephron glomerular filtration rate (SNGFR) were assessed in Munich-Wistar rats by direct glomerular puncture during perfusion of Henle's loop with isotonic Ringer's solution at rates of 0 and 40 nl/min. At the higher flow rate, SNGFR averaged only approximately 65% that measured during the lower flow rate. Whereas mean glomerular capillary hydraulic pressure was unaffected, both glomerular plasma flow rate and ultrafiltration coefficient Kf were found to decrease significantly in response to increase in loop perfusion rate, thereby accounting for the measured reduction in SNGFR. These changes were associated with increased afferent (RA) and efferent (RE) arteriolar resistances. Based on the close anatomic contact between mesangial cells and these arterioles, a single effector mechanism channeled through mesangial contractility is suggested to account for the observed reduction in Kf and increase in RA and RE. Mesangial contractility appears to be under sympathetic nerve control. In our recent micropuncture study with Munich-Wistar rats, a marked reduction in SNGFR was observed during high-frequency stimulation (5 Hz) of the renal nerve. This reduction in SNGFR was accompanied by a marked fall in Kf and increase in RA and RE. When kidneys were perfusion-fixed during high-frequency stimulation, a marked reduction in the number of open channels was demonstrated together with marked narrowing of afferent and efferent arterioles. These observations are consistent with the view that sympathetic innervation of mesangium may modulate GFR through its ability to regulate mesangial contractility.