NITRIC-OXIDE NERVES IN THE UTERUS ARE PARASYMPATHETIC, SENSORY, AND CONTAIN NEUROPEPTIDES

Nitric oxide (NO) is synthesized in neurons and is a potent relaxer of vascular and nonvascular smooth muscle. The uterus contains abundant NO-synthesizing nerves which could be autonomic and/or sensory. This s tudy was undertaken to determine: 1) the source(s) of NO-synthesizing nerves in the rat uterus and 2) what other neuropeptides or transmitte r markers might coexist with NO in these nerves. Retrograde axonal tra cing, utilizing Fluorogold injected into the uterine cervix, was emplo yed for identifying sources of uterine-projecting neurons. NO-synthesi zing nerves were visualized by staining for nicotinamide adenine dinuc leotide phosphate (reduced)-diaphorase (NADPH-d) and immunostaining wi th an antibody against neuronal/type I NO synthase (NOS). NADPH-d-posi tive perikarya and terminal fibers were NOS-immunoreactive (-I). Some NOS-I/NADPH-d-positive nerves in the uterus are parasympathetic and or iginate from neurons in the pelvic paracervical ganglia (PG) and some are sensory and originate from neurons in thoracic, lumbar, and sacral dorsal root ganglia. No evidence for NOS-I/NADPH-d-positive sympathet ic nerves in the uterus was obtained. Furthermore, double immunostaini ng revealed that in parasympathetic neurons, NOS-I/NADPH-d-reactivity coexists with vasoactive intestinal polypeptide, neuropeptide Y, and a cetylcholinesterase and in sensory nerves, NOS-I/NADPH-d-reactivity co exists with calcitonin generated peptide and substance P. In addition, tyrosine hydroxylase(TH)-I neurons of the PG do not contain NOS-I/NAD PH-d-reactivity, but some TH-I neurons are apposed by NOS-I varicositi es. These results suggest NO-synthesizing nerves in the uterus are aut onomic and sensory, and could play significant roles, possibly in conj unction with other putative transmitter agents, in the control of uter ine myometrium and vasculature.