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The effects of the age of induction and total duration of streptozotocin diabetes on the sympathetic noradrenergic innervation of the rat heart was examined with glyoxylic acid induced histofluorescence to demonstrate the distribution of noradrenergic fibers within the heart, and with high performance liquid chromatography with electrochemical detection to measure tissue levels of the neurotransmitter norepinephrine. Diabetes was induced in male Sprague-Dawley rats at 1, 2, and 4 months of age. Within each of these groups, diabetic rats survived for periods of 1, 2, and 4 months. Additional groups of diabetic rats survived to a chronological age of 8 months. Norepinephrine levels in the hearts of diabetic rats were increased over those of control rats in all groups at 1 month duration of diabetes. Ventricles were generally affected to a greater extent than atria. At 2 months duration of diabetes, ventricular levels remained elevated while atrial norepinephrine levels were at or below control levels. At 4 months duration of diabetes, and in all groups at 8 months of age, the norepinephrine levels were at or below control levels, except in the ventricles of rats induced at 4 months of age, which remained elevated. Histofluorescence studies demonstrated the presence of axon bundles and varicose noradrenergic profiles in the diabetic rat hearts, distributed in a pattern similar to that seen in controls. However, at 1 month duration of diabetes in all groups, the density of noradrenergic varicosities in diabetic rat hearts appeared increased with abundant branched profiles. These results are surprising, since studies on genetic models of diabetes have suggested decreased norepinephrine levels in the heart. The present study suggests that during the early phases of streptozotocin induced diabetes, noradrenergic nerves are still intact and may be susceptible to pharmacologic manipulation. The later fall of norepinephrine levels back to or below control levels may indicate actual neuronal damage, suggesting that early intervention may be necessary to protect these nerves from degeneration. This issue is potentially important in view of the reported toxic effects of high NE levels on the heart, and the high incidence of death from myocardial infarct in diabetic humans with autonomic neuropathy.

A golgi-Cox examination of the locus coeruleus in the spontaneously hypertensive rat (SHR) has shown an increase in the number of primary dendritic branches, in the number of secondary branch points, in the mean length of the dendritic branches from the soma to the outer extent of the secondary branches, and in the longest extent of the dendritic domain in comparison with the locus coeruleus in the Wistar-Kyoto normotensive rats at sixteen weeks of age. We suggest that the anatomical changes may provide a substrate for altered afferent relationships in the neurochemical regulation of neurons of the locus coeruleus, although it remains to be shown whether such alterations are related in any way to blood pressure. It appears evident that the altered mechanisms resulting in hypertension in this genetic model are more complex than an anatomical or neurochemical modification in one of the central autonomic nuclei. However, the present finding that anatomical alterations in the dendritic arborizations of a key nucleus such as the locus coeruleus occur, points towards a need for further examination of the interrelationships of specific neurotransmitter systems in this nucleus.

The rabbit appendix, a region of gut with well organized zones of lymphoid tissue, was examined with the glyoxylic acid histofluorescence technique for the localization of noradrenergic fibers, with high performance liquid chromatography with electrochemical detection (LCEC) for the quantitation of norepinephrine and serotonin, with Bielshowski and Giemsa stains for additional information about neural supply, and with acetylcholinesterase histochemistry for the localization of this hydrolytic enzyme. Fluorescent plexuses entered the serosal surface of the appendix associated with blood vessels, traveled longitudinally inside the muscularis interna, mainly in association with blood vessels but adjacent to enteric smooth muscle, and branched into long, linear, varicose plexuses that ran inward in a radial orientation towards the lumen in the internodular septa. As these fibers approached the interdomal regions near the epithelial surface, they passed through thymus-dependent cell zones, and arborized extensively throughout the interdomal region. A high density of varicosities was found in the subepithelial region where immunoglobulin-secreting plasma cells are found. These varicosities were sparse at 21 days of age, but were increased in number at 42 days of age. They were even further increased in number and density in adults. These fibers were further identified with a Bielshowski silver stain, and also demonstrated acetylcholinesterase activity. The noradrenergic varicosities in the interdomal regions of the adult rabbit appendix were closely associated with numerous yellow fluorescent cells of 25-40 microns diameter, which sometimes demonstrated fine varicose processes. The adult rabbit appendix contained a moderate concentration of norepinephrine (163.0 +/- 22.9 ng/g wet weight) and a very high concentration of serotonin (3981 +/- 283 ng/g wet weight). Levels in neonates were considerably lower, suggesting that the yellow fluorescent cells may contain serotonin. Acetylcholinesterase was associated with neural fibers and with non-neural regions of the lymph nodules and the domes, perhaps playing a protective role for these regions of the cellular immune system. The rabbit appendix is a well organized region of lymphoid tissue with specific zones of noradrenergic innervation and possible "paraneuronal" activity, with a readily accessible lumen for the isolation and collections of secretions. We propose this model as an excellent structure for further exploration of interactions between the nervous and immune systems.

Noradrenergic innervation of popliteal and mesenteric lymph nodes in mice was examined with fluorescence histochemistry. Dense varicose plexuses entered the nodes with the vasculature in the hilar region and continued with the vasculature into the medullary region. Fine, delicate varicosities and small vascular plexuses continued into the cortical and paracortical regions surrounding the germinal centers; some varicosities ended among lymphocytes. A subcapsular plexus contributed fibers into the cortical and paracortical regions. Chemical measurements revealed the presence of norepinephrine in lymph nodes that was depletable with 6-hydroxydopamine. Depletion of norepinephrine from lymph nodes with this agent resulted in a diminished primary immune response in draining lymph nodes following subcutaneous injection of an antigen in two mouse strains, but had no effect in two other strains. These findings suggest that noradrenergic fibers innervate both the vasculature and parenchymal regions of lymph nodes, and may participate in the modulation of immune responses in these organs.

Neurochemical analysis of norepinephrine and serotonin with high performance liquid chromatography with electrochemical detection (LCEC) in several microdissected central autonomic nuclei of 4 week old and 16 week old spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), and control normotensive Wistar rats (WIS), revealed some differences among these strains, but only one change that correlated with the hypertensive state. Norepinephrine levels in the 4 week old SHR were greater in the parabrachial nuclei and the dorsal motor nucleus of X than in the WKY, but levels in the WIS normotensive also were greater than in the WKY, and equalled levels in the SHR. In the 16 week old rats, no difference was noted between NE levels in the SHR and WKY strains, but levels in the locus coeruleus and parabrachial nuclei of the WIS were greater than in both the SHR and WKY. Serotonin levels in the 4 week old SHR and WKY rats did not differ, while levels in the paraventricular nucleus, locus coeruleus, parabrachial nuclei, and medullary raphe nuclei of the WIS rat were greater than one or both of these inbred strains. In the dorsal motor nucleus of X in 16 week old rats, serotonin levels were greater in the SHR than in either the WKY or WIS controls, suggesting one possible transmitter action that should be explored further for its potential relationship to the hypertensive state.(ABSTRACT TRUNCATED AT 250 WORDS)