REABSORPTION OF NITRO-L-ARGININE INFUSED INTO THE LATE PROXIMAL TUBULE PARTICIPATES IN MODULATION OF TGF RESPONSIVENESS

Previous studies indicate that endothelium-derived nitric oxide (NO) can directly modulate afferent arteriolar tone and that macula densa-derived NO can indirectly regulate afferent arteriolar tone by modulating the tubuloglomerular feedback (TGF) mechanism. The present in vivo micropuncture study evaluated whether the effect of late proximal tubular perfusion with the nitric oxide synthase (NOS) inhibitor, N-G-L-arginine (NLA), on TGF responsiveness is related to reabsorption of NLA. Late proximal perfusion of 10(-3) M NLA resulted in a gradual, time-dependent enhancement of maximum TGF-mediated decreases in stop-flow pressure (SFP) from -7.1 +/- 0.7 to - 19.4 +/- 1.6 mm Hg (P < 0.01). A detailed recording of SFP revealed that the maximum response during late proximal perfusion of NLA was obtained eight to nine minutes following the initiation of the perfusion, whereas maximum TGF responses evoked by late proximal perfusion with ATF were reached within one to two minutes. NLA infused into the late proximal segment of a neighboring nephron also resulted in enhancement of maximum SFP feedback responses from -5.5 +/- 0.5 to -10.4 +/- 1.9 mm Hg (P < 0.05), indicating that NLA can be reabsorbed and can consequently influence TGF responses. Finally, maximum SFP feedback responses were obtained prior to and following late proximal perfusion of 10(-3) M NLA dissolved in ATF, 10(-3) M NLA dissolved in 285 mM mannitol, and following perfusion with mannitol without NLA. Following perfusion with NLA in mannitol, the average TGF response was -14.0 +/- 1.8 mm Hg and significantly exceeded the control response (-6.4 +/- 1.2 mm Hg; P < 0.01); however, it was significantly less than the response obtained following perfusion with NLA in ATF (-24.9 +/- 1.8 mm Hg; P < 0.01). Summarizing, NLA infused into the late proximal tubules can greatly increase TGF responsiveness. Tubular reabsorption of NLA is essential for full expression of this effect, but how and where reabsorbed NLA interacts with the efferent limb of the TGF system remains to be established.