Background. We have shown previously that norepinephrine (NE) uptake activity is reduced in the failing right ventricle of animals with right heart failure (RHF) produced by tricuspid avulsion and progressive pulmonary constriction. However, it is unknown whether this defect in neuronal NE uptake is related to reduction of noradrenergic nerve terminals or whether these changes also occur in animals with left heart failure (LHIF). It is also unknown whether increased NE release in heart failure contributes to the noradrenergic nerve abnormalities.Methods and Results. We measured myocardial NE content, NE uptake function, and noradrenergic nerve profiles in dogs with either RHF or LHF induced by rapid ventricular pacing. NE uptake activity was

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FMRFamide-like immunoreactivity (FLI) and the colocalization of FMRFamide and substance P-like (SPLI) immunoreactivities were examined in the brain and lateral eye of the horseshoe crab with FITC- and TRITC-labeled secondary antibody techniques. In the brain, fibers with FLI were localized in the neuropils of the lamina, medulla, central body, corpus pedunculatum, optic tract, circumesophageal connective, and central neuropil. An extensive network of reactive fibers innervatives the brain's vascular sheath. Somata with FLI were found in the dorsal medial group, dorsal lateral posterior groups #1 and #2, and ventral posterior lateral groups #1 and #2. Several distinct subgroups of reactive somata were noted in both the medullar and ventral medial groups. The distribution of fibers in the brain with colocalized FLI and SPLI includes those which innervate the vascular sheath and widespread populations of small-diameter beaded fibers in the central neuropil and circumesophageal connective. Somata with colocalized FLI and SPLI constitute minority populations in the medullar and dorsal medial groups but form the majority population of a subgroup in the ventral medial group. Overall localization of SPLI was reevaluated and is reported here according to the nomenclature of the new Chamberlain and Wyse brain atlas. In addition to those previously reported, somata with SPLI were found in the dorsal lateral posterior groups #1 and #2, the ventral lateral posterior groups #1 and #2, and several distinct subgroups of the medial and ventral medial groups. In the retina of the lateral eye, fibers with both FLI and SPLI ramify in the lateral plexus and ultimately innervate the corneal epidermis. Brain homogenates were examined for immunoreactive (ir) FMRFamide and ir-substance P with radioimmunoassay techniques. Ir-FMRFamide and ir-substance P eluted in different fractions from both gel filtration chromatography and HPLC. Furthermore, the binding curves for both substances were similar to those of the corresponding synthetic compounds. Brain homogenates were also bioassayed on the lateral eye. Three gel filtration fractions mimic natural circadian activity by increasing the sensitivity of the lateral eye, but they were not coincident with ir-FMRFamide or ir-substance P. Although it is not completely resolved what the active molecules in these fractions are, it is clear that neither ir-FMRFamide nor ir-substance P is a possible candidate.

Serotoninlike immunoreactivity was examined by the fluorescein-isothiocyanate-labeled secondary antibody technique in the lateral eye and brain of Limulus. Endogenous serotonin was measured with high-performance liquid chromatography and electrochemical detection. The synthesis of [3H]serotonin from [3H]tryptophan was measured in the presence and absence of reserpine. Fibers with serotoninlike immunoreactivity were found in the proximal stalks of the corpora pedunculata, in the neuropil of the central body, in the neuropils of the visual centers (lamina, medulla, and ocellar ganglion), in the optic tract that connects the ocellar ganglion with the posterior medial medulla, and in the central neuropil of the brain. Immunoreactive somata were found in four groups in the brain. Up to 50 somata were scattered through each side of the dorsal medial group that lies centered on the dorsal surface within the curve of the central body. These neurons innervate the central body neuropil and send processes into the central neuropil. Three or four reactive somata formed the ventral pole of each medullar group. These may provide the innervation of the proximal stalk of the corpora pedunculata. Five to ten reactive neurons were observed anteriorly in the ventral posterior lateral group #2 on each side that send processes into the central neuropil. Ten to 15 reactive somata were found on either side of the midline in the dorsal anterior part of the ventral medial group that contribute processes to the central neuropil. The remainder of the brain was not immunoreactive. No immunoreactive fibers or somata were found in the lateral eye or in the lateral optic nerve. Serotoninlike and substance P-like immunoreactivities were not found to be colocalized anywhere in the brain. Significant amounts of endogenous serotonin were detected in the lamina and medulla whose neuropils are rich in immunoreactive fibers and in the central body and dorsal medial group that are also rich in immunoreactive somata and fibers. No endogenous serotonin was detected in either the lateral eye or the lateral optic nerve. The lamina, medulla, and central body and dorsal medial group also synthesized and stored [3H]serotonin from [3H]tryptophan. It is likely that serotonin is a neurotransmitter in the brain, but not in the lateral eye of the horseshoe crab. In particular, it appears that serotoninergic neurons may play a role in central visual processing.