Vasoactive intestinal polypeptide nerve fibers in human and monkey (Macaca fascicularis and Macaca mulatta) kidneys.

Nerve fibers immunoreactive for vasoactive intestinal polypeptide (VIP) were demonstrated for the first time by the indirect immunofluorescence technique in human and monkey kidneys. VIP-immunoreactive nerve fibers showing varicosities were observed in the adventitia of arcuate arteries and their branches. The density of VIP-immunoreactive nerve fibers decreased from the juxtamedullary region to the cortex. Occasionally a VIP-immunoreactive varicose nerve fiber was observed near the vascular pole of a glomerulus, but no direct innervation of afferent or efferent arterioles in either monkey or human kidney was found. The distribution of VIP-immunoreactive nerve fibers in the monkey and human kidneys was similar to that reported in other species, with less density. The functional role of VIP in the innervation of the kidney is not known, but various suggestions have been made regarding the possible involvement of VIP on vasodilation of selective intrarenal blood vessels, renin secretion, and/or effects on tubules. While none of these questions were established at this time they would appear to be logical areas for further study.

Neuropeptide Y (NPY)-like immunoreactive nerve fibers in the human and monkey (Macaca fascicularis) kidney.

Nerve fibers immunoreactive for neuropeptide Y (NPY) are demonstrated for the first time by the indirect immunofluorescence technique in the human and monkey kidney. NPY-like immunoactivity (NPY-LI) is shown in a bundle of nerve fibers in the surrounding connective tissue of arteries and to a lesser extent, veins, mainly at the juxtamedullary region. Varicose nerve terminals are shown associated with blood vessels and passing between tubules in the mid and lower cortex. NPY-LI nerve fibers are also seen surrounding afferent and occasionally efferent arterioles at the vascular pole of the glomeruli. The distribution of NPY-LI nerve fibers in the monkey and human kidneys is similar to that of other species, only the quantity of the nerve fibers varies.

Effect of copper deficiency on the lymphatic absorption of cholesterol, plasma chylomicron clearance, and postheparin lipase activities.

The lymphatic absorption of cholesterol and plasma clearance of chylomicrons were investigated in Cu-deficient rats (CuD) fed 0.5 mg Cu/kg diet, as compared with Cu-adequate control rats (CuA) fed 7.5 mg/kg diet. Cholesterol absorption was measured by the 14C-radioactivity appearing in the mesenteric lymph at hourly intervals for 8 hr after an intraduodenal dose of [14C]cholesterol. The plasma clearance of chylomicrons was measured at 3, 6, and 10 min after an intravenous dose of chylomicrons labeled in vivo with [3H]retinyl ester. Cumulative [14C]cholesterol absorption and total lymphatic output of cholesterol were significantly decreased in CuD at 4 hr and thereafter, with no change in percentage distribution of free and esterified cholesterol. Over an 8-hr period, 7.3% of the dose was absorbed by CuD and 9.2% by CuA. When [3H]chylomicrons, obtained from a CuD or CuA donor rat, were injected into CuD and CuA recipient rats, the label was cleared faster in CuD during the first 3 min. At 6 and 10 min, however, no significant difference in percentage clearance of the dose was observed between the groups. The half-life (t1/2) of [3H]chylomicrons and the total 3H-radioactivity taken up by the liver during the entire 10-min period did not differ between the groups, regardless of the source of chylomicrons. The activities of both endothelial lipoprotein lipase (LPL) and hepatic lipase (HL) in postheparin plasma were markedly lower in CuD. As expressed in micromoles fatty acid released/hr/ml plasma, the activities of LPL in CuD and CuA were 32.6 +/- 1.9 and 45.6 +/- 1.3, respectively. A similar magnitude of difference was also observed in HL activity. The data provide evidence that copper deficiency impairs the intestinal transport of cholesterol and the peripheral lipolysis of chylomicrons. The data, however, strongly suggest that the hepatic uptake of chylomicron remnants via the apo-E-dependent mechanism may not be impaired in Cu deficiency.

Effect of marginal zinc deficiency on the apolipoprotein-B content and size of mesenteric lymph chylomicrons in adult rats.

To investigate the mechanisms underlining the impaired intestinal absorption of lipids in zinc deficiency, the apo-B content and chemical composition of chylomicrons from marginally zinc-deficient rats fed 2.8 ppm of dietary zinc (ZD) were compared with those from pair-fed (PF) and ad libitum control (CT) groups fed an adequate level (30.8 ppm) of zinc. Chylomicrons, obtained by cannulating the mesenteric lymph, were isolated by ultracentrifugation at 1.3 X 10(6) g/min at 12 C and purified by 2% agarose column chromatography. Apolipoprotein- (apo) B was separated by the method of isopropanol precipitation. The apo-B concentration of chylomicrons was lowered significantly in ZD group. The apo-B contents of chylomicrons in ZD, PF and CT rats, as expressed as % chylomicron protein, were 8.7 +/- 0.1, 11.5 +/- 0.5 and 10.7 +/- 0.7%, respectively. No significant differences were noted between ZD and PF groups in total protein (TP), phospholipid (PL), triglyceride (TG) and cholesterol (CH), although there was a slight decrease in TG and an increase in CH in CT rats compared with ZD and PF groups. The ratio of the core to surface constituents, as determined by TG/(TP + PL), was significantly higher in ZD group relative to the controls, suggesting that chylomicrons from ZD rats were larger. This finding was consistent with the appearance of larger chylomicron particles in the lacteal of the intestinal mucosa following lipid ingestion. These findings suggest that the intestinal synthesis of apo-B may be defective in zinc-deficient rats and may explain in part the impaired absorption of dietary lipids observed in zinc deficiency.

Effect of marginal zinc deficiency on the lymphatic absorption of [14C]cholesterol.

The effect of zinc deficiency on intestinal absorption of cholesterol was investigated in adult male rats fed 3.6 ppm of dietary zinc (ZD) and compared with pair-fed (PF) and ad-libitum (CT) controls fed 30.6 ppm of zinc for 10 to 12 wk. The intestinal absorption of cholesterol was measured by collecting the mesenteric lymph at hourly intervals for 8 h after infusing a dose of [14C]cholesterol in a lipid emulsion through an indwelling duodenal catheter. Data on the hourly lymphatic output of [14C]cholesterol showed that the absorption of [14C]cholesterol plateaued at 4 h postdosing in all groups. The rate of the appearance of [14C]cholesterol in the mesenteric lymph significantly decreased in ZD rats at 5 h and thereafter. The cumulative absorption of [14C]cholesterol by ZD rats for the 8-h period was 4.4 +/- 1.0% of the dose, compared with 11.8 +/- 1.1% by PF and 10.7 +/- 1.4% by CT rats. There were no differences in percent distribution of esterified [14C]cholesterol among the three groups. Also, no significant change in mucosal cholesterol esterase activity was observed due to zinc deficiency. The present data and previous findings taken together suggest that the primary mechanism responsible for the impaired absorption of cholesterol may be associated with defective formation of chylomicrons in the intestinal mucosa.

Delayed plasma clearance and hepatic uptake of lymph chylomicron 14C-cholesterol in marginally zinc-deficient rats.

Previously, chylomicrons from marginally zinc-deficient rats were shown to be abnormally large, with markedly reduced levels of apoproteins C and E. In the present study, effects of such changes on the plasma clearance and hepatic uptake of chylomicron cholesterol were investigated in rats fed 3 ppm of zinc (ZD), as compared with those fed 30 ppm of zinc (CT). The rate of plasma clearance was determined by plasma 14C-radioactivity at different intervals after intravenous injection of lymph chylomicrons labeled in vivo with 14C-cholesterol. The 14C-clearance curves were nonlinear, consisting of an initial rapid phase followed by a slow phase of clearance. The initial 14C-clearance was significantly (p less than 0.05) delayed whether the labeled chylomicrons from ZD donors were injected into ZD or CT recipients. The hepatic 14C-recovery in extracted lipids was also significantly lower in ZD rats. The present data provide first evidence that a marginal level of zinc deficiency produces a significant delay in the plasma clearance and hepatic uptake of chylomicron cholesterol. This may be attributable in part to the molecular alterations of chylomicrons induced by zinc deficiency.

Effect of marginal zinc deficiency on the morphological characteristics of intestinal nascent chylomicrons and distribution of soluble apoproteins of lymph chylomicrons.

Effects of marginal zinc depletion on the compositional and morphological characteristics of chylomicrons were investigated in adult male rats fed 3 ppm of dietary zinc, as compared with pair-fed and ad-libitum controls given 30 ppm of zinc for 6 to 8 wk. Lymph was collected by cannulating the intestinal lymphatic duct during infusion of a 1:1 mixture of Intralipid and 150 mM NaCl via a duodenal catheter. Lymph chylomicrons were isolated by ultracentrifugation and further purified by agarose column chromatography. A marginal level of zinc deficiency produced decreases in the relative concentrations of apolipoproteins C and E, with an increase in apoprotein A-I and no change in apoprotein A-IV and no significant alterations in the lipid components. Nascent chylomicrons in the intestinal absorptive cells were irregular and larger in shape and size, as determined by light and electron microscopy. The present results suggest that the changes in chylomicron apoproteins produced by zinc deficiency are due in part to postsynthetic modification of intestinal chylomicrons upon their release into the lymph.

Acetylcholinesterase activity of primary sensory neurons and dorsal root fibers in the cat.

Dorsal roots and spinal ganglion cells of adult cats were studied for acetylcholinesterase (AChE) content. An inverse correlation exists between cell size and AChE activity; large neurons are AChE-negative whereas small ones are intensely AChE-positive. A few AChE-positive fibers were demonstrated in the dorsal roots. A possible correlation between AChE activity and substance P content of primary sensory neurons is discussed.

Norepinephrine depletion in idiopathic orthostatic hypotension.

Five patients with idiopathic orthostatic hypotension and defective vasoconstrictor responses to the Valsalva maneuver and to application of ice to the forehead were found to have absent vasoconstriction in the forearm in response to intra-arterial administration of tyramine and enhanced vasoconstrictor responses in response to intra-arterial administration of norepinephrine. These findings strongly suggested norepinephrine depletion from the nerve endings and inability of the sympathetic nerve endings to take up norepinephrine. The depletion of norepinephrine from sympathetic nerve endings was confirmed in four patients by demonstrating histochemically the absence of catecholamine-specific fluorescence in sympathetic vasomotor nerves from deltoid muscle. It is suggested that depletion of norepinephrine from nerve endings was responsible for autonomic dysfunction and orthostatic hypotension in these patients.

Adrenergic and cholinergic innervation of the hamster Harderian gland.

Examination of Harderian glands of adult male and female golden hamsters by appropriate histochemical techniques reveals that adrenergic nerves are associated only with the blood vessels. Acetylcholinesterase-positive fibers are present in the connective tissue surrounding the gland, along the ducts, and among the acini.