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In this study, we examined the effect of intracerebroventricular (ICV) injection of 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, or compound C (CC), an AMPK inhibitor, on the activity of sympathetic nerves innervating the adrenal gland and kidney in urethane-anesthetized rats to elucidate the role of AMPK in sympathetic nervous system function. We found that an ICV injection of AICAR or CC significantly stimulated renal sympathetic nerve activity (RSNA) and adrenal sympathetic nerve activity (ASNA) in a dose-dependent manner. Following this, we examined the role of AMPK on the sympatho-excitation caused by leptin injection. Pretreatment with AICAR or CC eliminated the leptin-induced increase in RSNA, however, neither pretreatment with AICAR or CC affected the leptin-induced increase in ASNA. Our data suggest that AMPK may regulate the sympathetic nerve system, and that the stimulating effect of leptin on sympathetic nerve activity in kidney may depend on central AMPK., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Several studies have suggested a role for cholinesterases in regulating neurite outgrowth. Some acetylcholinesterase (AChE) inhibitors can inhibit neurite outgrowth, but it is unclear if this is due to inhibition of AChE. In this study, the effect of cholinesterase inhibitors on neurite outgrowth from chick sympathetic neurons was examined. Very high (micromolar) concentrations of tacrine and BW284c51 were needed to inhibit neurite outgrowth. In contrast, nanomolar concentrations were required to block cholinesterase activity. No correlation was found between the type of inhibitor or potency of cholinesterase inhibition and inhibition of neurite outgrowth. Both tacrine and BW284c51 were neurotoxic at concentrations that inhibited outgrowth. Therefore, the action of cholinesterase inhibitors on neurite outgrowth may be due to non-specific toxicity rather than to cholinesterase binding.

Transplacental exposure to diethylstilbestrol (DES) causes morphological and functional changes including the disruption of follicular maturation in murine ovaries. Since the function of ovarian sympathetic nerves is thought to be related to the follicular maturation, we examined changes in the distribution pattern of the sympathetic nerves between prenatally DES-exposed rat ovaries and normal controls using immunohistochemistry of tyrosine hydroxylase (TH). In the DES-exposed ovaries, the TH-positive nerve innervation was poor and the innervation density was reduced to about half as compared to that in the controls. Simultaneously, follicular maturation was disrupted in the DES-exposed ovaries. These findings suggest that the prenatal DES exposure inhibited the development of ovarian sympathetic nervous system, which might be closely associated with the disruption of follicular maturation.

The central roles of nitric oxide (NO) in regulations of the blood pressure and heart rate were examined in anesthetized rats. Intracerebroventricular (i.c.v.) injection of Nomega-nitro-L-arginine methyl ester (L-NAME) caused dose-dependent increase in the blood pressure and heart rate. The pressor response of the blood pressure to L-NAME (2 micromol, i.c.v.) was reduced by L-arginine (5 micromol, i.c.v). Pretreatment with a ganglionic blocker, pentolinium (10 mg/kg, i.v.), significantly inhibited both pressor responses induced by L-NAME (2 micromol, i.c.v). The later pressor response of the blood pressure to L-NAME was also inhibited by the angiotensin II AT-1 blocker losartan (10 mg/kg, i.v). These results suggest that the response of the blood pressure to L-NAME is mediated by both the sympathetic nervous system and the renin-angiotensin system.

Nitric oxide synthase-immunoreactivity (NOS-IR) was detected in strands of nerve fibers entering the rat superior cervical ganglia (SCG) and in nerve fibers forming a plexus beneath the capsule of adrenal glands. Within the SCG, varicose NOS-IR fibers encircled virtually all postganglionic neurons and small diameter cells, presumably small intensely fluorescent (SIF) cells. Perikarya of SIF cells exhibited strong NOS-IR, whereas the level appeared to be low in postganglionic neurons. Decentralization of the SCG for 4-6 days markedly reduced the number as well as the intensity of NOS-IR fibers without causing a detectable change of NOS-IR in the postganglionic neurons and SIF cells. Beneath the adrenal capsule, bundles of NOS-IR fibers bifurcated and made a sharp turn to reach the adrenal medulla. Chromaffin cells, which themselves exhibited fairly strong NOS-IR, appeared to be surrounded by NOS-IR fibers. The result shows that NOS-IR is present in pre- and post-synaptic elements of the sympathetic ganglia and adrenal medulla, representing a complex system that may regulate the activity of ganglionic neurons and chromaffin cells via a number of sites of action.

An indirect immunohistochemical method was used to visualize nerves immunoreactive for tyrosine hydroxylase (THI) and dopamine-beta-hydroxylase (DBHI) in kidney sections of cats 6 weeks and 2 and 3 months of age. THI and DBHI nerve terminals innervate the renal pelvis, interlobar veins and arterial tree including medullary vascular bundles of cats of each age studied. In kidneys of 6-week-old cats, THI and DBHI axons form elaborate plexuses that are distributed throughout much of the inner medulla, whereas some medullary axons appear to degenerate at 2 months and no inner medullary plexuses were visualized in 3-month-old cats. Transitory inner medullary nerves in the cat kidney may influence cellular development and play a role in salt and water balance.

To determine whether dihydroxyphenylalanine (DOPA) decarboxylase (DDC) activity in the terminal regions of noradrenergic axons varies with axonal length, we compared the pattern of immunohistochemical staining for DDC in the 'short' terminal nerves of dog vas deferens with that in the 'long' nerves of spleen and atrium. The terminal nerves supplying the muscular coats of the vas deferens were, like those in spleen and heart, devoid of DDC immunoreactivity. The presence of this enzyme is therefore not characteristic of either short or long noradrenergic axons, in support of previous evidence that it is a specific marker for dopaminergic terminal nerves. Many axons supplying the mucosal epithelial cells in the vas deferens were DDC-positive, suggesting the existence of a dopaminergic innervation.

We have compared the pattern of neural catecholamine fluorescence with that of immunoreactivity for the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and DOPA decarboxylase (DDC) in dog atrium, which is innervated by noradrenergic nerves, and in dog kidney, which is thought to be supplied by dopaminergic nerves as well. In both tissues the distribution of nerves containing catecholamine fluorescence was similar to that of nerves exhibiting TH-like immunoreactivity. By contrast, DDC-like immunoreactivity was present in some (but not all) of the nerves associated with the intrarenal blood vessels, but was not detectable in any atrial nerves. High DDC activity provides further confirmation of the existence of sympathetic dopaminergic neurons supplying the kidney.