Nitric oxide modulates renal sensory nerve fibers by mechanisms related to substance P receptor activation
Nerve terminals containing neuronal nitric oxide synthase (nNOS) are localized in the renal pelvic wall where the sensory nerves containing substance P and calcitonin gene-related peptide (CGRP) are found. We examined whether nNOS is colocalized with substance P and CGRP. All renal pelvic nerve fibers that contained nNOS-like immunoreactivity (-LI) also contained substance P-LI and CGRP-LI. In anesthetized rats, renal pelvic perfusion with the nNOS inhibitor S-methyl-l-thiocitrulline (l-SMTC, 20 μM) prolonged the afferent renal nerve activity (ARNA) response to a 3-min period of increased renal pelvic pressure from 5 ± 0.4 to 21 ± 2 min ( P < 0.01, n = 14). The magnitude of the ARNA response was unaffected byl-SMTC. Similar effects were produced by N ω-nitro-l-arginine methyl ester (l-NAME) but not d-NAME. Increasing renal pelvic pressure produced similar increases in renal pelvic release of substance P before and during l-SMTC, from 5.9 ± 1.4 to 13.6 ± 4.2 pg/min before and from 4.9 ± to 12.6 ± 2.7 pg/min during l-SMTC. l-SMTC also prolonged the ARNA response to renal pelvic perfusion with substance P (3 μM) from 1.2 ± 0.2 to 5.6 ± 1.1 min ( P < 0.01, n = 9) without affecting the magnitude of the ARNA response. In conclusion: activation of NO may function as an inhibitory neurotransmitter regulating the activation of renal mechanosensory nerve fibers by mechanisms related to activation of substance P receptors.