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 microM) 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 by L-SMTC. Similar effects were produced by N(omega)-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 microM) from 1.2 +/- 0.2 to 5.6 +/- 1.1 min (P < 0.01, n = 9) without affecting the magnitude of the ARNA response.


CONCLUSIONS
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.
Kopp
U C
UC
Department of Internal Medicine, Department of Veterans Affairs Medical Center, Iowa City; University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
Cicha
M Z
MZ
Smith
L A
LA
Hökfelt
T
T
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000166:cytology; D007668:Kidney / Q000294:innervation* / Q000502:physiology; D008297:Male; D008465:Mechanoreceptors / Q000737:chemistry / Q000502:physiology; D009412:Nerve Fibers / Q000737:chemistry / Q000201:enzymology*; D009475:Neurons, Afferent / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013373:Substance P / Q000032:analysis
D018040:Receptors, Neurokinin-1; D009569:Nitric Oxide; D013373:Substance P; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D015740:Calcitonin Gene-Related Peptide