The innervation of the renal cortex in the dog

Cell Tissue Res (1988) 253:539-546 Cell and Tissue ResealT �9 Springer-Verlag 1988

The innervation of the renal cortex in the dog An ultrastructural study

Meredith Ferguson, G.B. Ryan, and C. Bell Departments of Physiology and Anatomy, University of Melbourne Medical Centre, Parkville, Victoria, Australia

Summary. Two cytochemical techniques were used at the ultrastructural level to study the distribution of specific axon types to different intrarenal structures in the dog. Us- ing the chromaffin reaction to distinguish catecholaminergic fibres from other axon populations, it was found that the renal cortex of the dog is supplied only by catecholaminergic nerves. Immunostaining for tyrosine hydroxylase (TH) labelled all of the intracortical nerves, and 20% to 25% of these profiles also contained dopa decarboxylase (DDC)-immunoreactivity, indicating they were dopaminergic rather than noradrenergic. Both DDC-positive and DDC-negative axons were seen in close association (~80 nm) with blood vessels and juxtaglomerular cells as well as tubular epithelial cells. The distribution of TH- and DDC-immunoreactive nerves in the renal cortex is compati- ble with existing functional evidence indicating that both dopaminergic and noradrenergic nerves are involved in the regulation of renal blood flow, tubular reabsorption and renin release.

Key words: Kidney - Renal innervation - Catecholamine- synthesizing enzymes - Dopamine - Immunohistochemistry

Dog

Renal function is well known to be modulated by reflex activation of the sympathetic nervous system (DiBona 1982), and previous investigators have examined the loca- tion and appearance of nerves in the renal cortices of the rat and monkey by light and electron microscopy (Barajas and Wang 1975; Mfiller and Barajas 1972). As much of the functional evidence regarding the neural control of renal function derives from experiments performed on the dog (e.g., Imbs et al. 1975; DiBona 1977; Mizoguchi et al. 1983 ; Bradley and Hjemdahl 1984), a detailed study of the innervation of the renal cortex in this species is clearly needed. However, to date, only the results of fluorescence-microscopic studies (McKenna and Angelakos 1968 a; Ljungquist and Wgtgermark 1970; Dole~el et al. 1976) have been reported.

Send offprint requests to: Meredith Ferguson, Department of Anat- omy, University of Melbourne Medical Centre, Parkville, Victoria, 3052, Australia

In our investigation, two ultrastructural cytochemical methods have been used to study the distribution of specific axon types to different structures in the dog renal cortex. The first is the chromaffin reaction (Tranzer and Richards 1975), a method by which catecholaminergic axons can be distinguished from other autonomic axon populations and from sensory axons. The second is the immunocytochemical localization of the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and dopa decarboxylase (DDC), which enables different classes of catecholaminergic axons to be distinguished (Hrkfelt et al. 1975; Jaeger et al. 1984).

Materials and methods

Chromaffin reaction

It is a characteristic of catecholamine storage granules that they form an electron-dense precipitate when exposed to chromate ions (Bloom 1970). This so-called "chromaffin reaction" (Tranzer and Richards 1975) identifies catecholaminergic axons by the presence of dense-core synaptic vesicles in the axon varicosity. The ease with which these axons can be visualized is enhanced further if the whole animal is pretreated with 6-hydroxydopamine: this amine is selec- tively taken up by the axonal membrane amine pump (Jons- son and Sachs 1970) and stored in the catecholamine storage vesicles where it greatly increases the intensity and ex- tent of vesicular dense cores (Bennett et al. 1970).

Tissue preparation

Twelve adult mongrel dogs were anaesthetized with sodium pentobarbitone (Nembutal, Abbott 40 mg/kg i.v.), and injected with 6-hydroxydopamine hydrobromide (Sigma, St. Louis, Mo. USA, 30 mg/kg i.v.). Thirty minutes later the left kidney was perfused with 1000 ml ice-cold phosphate-buffered saline (pH 7.6), followed by 1500 ml of an ice-cold mixture of 4% paraformaldehyde and 0.1% glutar- aldehyde. The kidney was thinly sliced and placed into a 4% solution of potassium dichromate for 6 h, and sectioned at 50 txm on a Vibratome. Either immediately, or after immunohistochemical incubation, sections were postfixed for 1 h in 2% osmium tetroxide and flat-embedded in Araldite. Ultrathin sections were counterstained with uranyl acetate and lead citrate and examined with a Philips 400 electron microscope.

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Immunohistochemistry

Vibratome sections were stained for TH- or DDC-like immunoreactivity by an indirect immunoperoxidase method. The TH antiserum (Eugene Tech International, Allendale, New Jersey, USA) was raised in rabbits against tyrosine hydroxylase purified from bovine adrenal glands. The prop- erties of the antiserum have been characterized in detail elsewhere (Joh and Ross 1983). The D D C antiserum was raised in guinea pigs against porcine kidney D D C in our laboratory, and its specificity and reactivity have been detailed elsewhere (Harris et al. 1986). The sections were incu- bated for 20 min in a 1:20 dilution of normal swine or rabbit serum, followed by an incubation for 4 h at room temperature in a 1 : 60 dilution of TH antiserum or a 1 : 250 dilution of D D C antiserum. The sections were then placed in a 1:50 dilution of horseradish peroxidase-conjugated anti-rabbit or anti-guinea pig immunoglobulins (Dako- patts) for 20 min and the bound peroxidase was visualized by incubation for 8 rain in 3,3'-diaminobenzidine. All re- agents and antisera were diluted in phosphate-buffered saline (pH 7.6).

As a control for non-specific staining, sections were pro- cessed as described, except for the substitution of the appro- priate pre-immune serum for primary antiserum. No immunoreactive nerves were seen under these circumstances.

F rom each of the 12 animals, 10 ultrathin sections of the renal cortex were examined for TH-immunoreactivity, and 10 ultrathin sections were examined for DDC-immunoreactivity.

Quantitation of axon distributions

The numbers of axon varicosities associated with arcuate and interlobular arteries, juxtaglomerular arterioles and proximal and distal tubules were counted. The criteria used to denote a probable neuroeffector relationship were the presence of synaptic vesicles within the axon profile and the absence of any Schwann cell or connective tissue elements between the membranes of axon and putative effector cell (Bennett 1972; Luff et al. 1987). Approximately one in fifty varicosities were single axons completely bare of Schwann cell that lay near both a vascular muscle cell and a tubular epithelial cell. As such axons could not be as- signed specificially to either target cell, and their rareness meant that they had a negligible effect on the results, these axons were excluded from the counts.

Results

Distribution of catecholaminergic axons

All of the axon profiles observed in the renal cortex were non-myelinated and had the appearance characteristic of varicose axons. Varicosities were often observed associated with the smooth muscle cells of the afferent and efferent arterioles and the arcuate and interlobular arteries (Fig. 1 a). Varicosities were commonly seen lying near juxtaglomerular cells in the afferent arteriole wall (Fig. 1 b). The juxtaglomerular cells of dogs in this study contained very little renin granulation, an observation in agreement with previous investigations (Alcorn etal . 1986; Goor- maghtigh 1939). These cells often contained large cisternae of endoplasmic reticulum, multivesicular bodies and one or two large lysosomes.

In addition to the axons that ran close to intra-cortical blood vessels, varicosities were also observed less frequently lying close to proximal and distal tubular epithelial cells (Fig. 1 c). In tissue from each of 10 animals, the distribution of all varicosities seen in a total o f 10 ultrathin sections was examined. The number of varicosities associated with vascular smooth muscle cells and tubular epithelial cells, respectively, ranged from 14:1 to 6:1 in different animals (mean 9:1). This ratio was similar whether the incidence of vascular varicosities was compared with that of varicosities associated with either proximal or distal tubules.

The intracortical axons were seen singly or in bundles, partially or totally surrounded by Schwann cell. The number of axons in each bundle ranged from 2 to 25. The diameter of the axons varied from 0.25 lam to 1.5 ~tm. The single profiles were observed less often than bundles, and were usually bare of Schwann cell, particularly when lying close (less than 150 nm) to a potential target cell. The majority of axons (73%) lay between 150 nm and 500 nm dis- tant from the effector cell, with a smaller proport ion (27%) of axons lying 80 nm to 150 nm away. These distances in- clude the thickness of the axon and effector cell basal laminae as well as the intercellular gap. Occasionally, only material of basal laminae separated the axon from the intrarenal structure (Fig. 1 a).

Profiles sectioned through a varicose region always contained numerous small dense-core synaptic vesicles with diameters of 40-60 nm, and a few large dense-core vesicles with diameters of 80-100 nm (Fig. 1 a-c). All of the profiles present were therefore assumed to be catecholaminergic.

Tyrosine hydroxylase-irnmunoreactive axons

All of the intracortical varicosities observed were immunoreactive for TH. Reaction product was spread throughout the cytoplasm and was not associated with any particular organelle (Fig. 2a, b). No reaction product was observed in intervaricose regions of any axon.

Dopa decarboxylase-immunoreactive axons

Some intracortical varicosities were DDC-positive. As with the immunohistochemical staining for TH, the reaction product was cytoplasmic, and was not associated with any organelle. DDC-immunoreactive varicosities were observed lying near juxtaglomerular cells (Fig. 3 a), the smooth muscle cells in the wall of the afferent and efferent arterioles and arcuate and interlobular arteries (Fig. 3 b) and, less frequently, with proximal and distal tubules (Fig. 3c). In all cases, however, DDC-negative profiles predominated. Both types of profile were usually seen in the same axon bundle (Fig. 3d).

Quantification of TH- and DDC-irnmunoreactive axons

The numbers of TH- and DDC-immunoreactive profiles were counted in tissue from 10 animals. For each animal, a total of 200 profiles was counted from 10 sections stained for TH, and a total of 200 profiles was counted from 10 sections stained for DDC. All of the profiles were immunoreactive for TH. By contrast, only 2 5 _ 2.0% of the profiles associated with the juxtaglomerular arterioles, 22-1-1.6% of the profiles lying near arcuate and interlobular arteries, and 20+_2.0% of the profiles associated with the renal tubules were immunoreactive for DDC.

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Fig. 1 a--c. Typical appearance of axons associated with different structures in the renal cortex. All of the varicosities contain dense- core vesicles and were therefore considered to be catecholaminergic. a Varicosities lying near smooth muscle cells in the wall of the afferent arteriole (A). Only basal lamina separates the varicosities from the smooth muscle cell. A distal tubule (D) is seen at the top of the figure, x 34000. b Varicosities associated with a juxtaglomerular cell (J). A proximal tubule (P) is seen on the right side of the figure, x 34000. e An axon bundle containing a number of varicose and intervaricose regions (/), running alongside a distal tubule (D). x 34000. Bar=0.5 gm

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Fig. 2a, b. Typical appearance of axons in the renal cortex following the chromaffin reaction and immunostaining for tyrosine hydroxylase immunoreactivity, a At low magnification, TH- immunoreactivity is seen in all axons, either singly (arrow) or in a bundle. Afferent arteriole (A). x 16000. b At higher

magnification, all of these varicosities also contain small and large dense-core synaptic vesicles. Note that the immunohistochemical reaction product is spread throughout the cytoplasm and is not associated with any particular organelle. Afferent arteriole (A). x 29300. Bar=0.5 ~tm

Discussion

We have observed no myel inated axons in the renal cortex of the dog. Fur thermore , all axon varicosities present contained chromaffin-posi t ive vesicles and TH-immunoreact iv- ity, confirming that they represented catecholaminergic neurons. Al though a small number of TH-posi t ive neurons has been described in the dorsal root ganglia of the rat (Price and Mudge 1983), there is no evidence for such neurons consti tut ing a major sensory populat ion. Our data therefore suggest that all the axons seen in dog renal cortex

are likely to be sympathetic. This finding is similar to previous observations made in the rat kidney, where the sensory nerve supply is virtually completely restricted to the renal pelvis (Ferguson and Bell 1985; Ferguson et al. 1986). Nu- merous non-myelinated, putat ive sensory, axons are also present in the wall of the dog renal pelvis (M. Ferguson, unpublished data).

Acetylcholinesterase-containing nerves have been identified in the dog renal cortex, suggesting that the kidney re- ceives a cholinergic innervation (McKenna and Angelakos 1968; Weitsen and Norvell 1969). However, a number of

Fig. 3a--d. Typical appearance of axons in the renal cortex following the chromaffin reaction and immunostaining for dopa decarboxylase immunoreactivity, a A DDC-positive varicosity (arrow) and DDC-negative varicosity associated with a juxtaglomerular cell (J). Only basal lamina separates the DDC positive axon from the juxtaglomerular cell. The varicosity is bare of Schwann cell on the side apposed to the juxtaglomerular cell. x 30000. b A DDC-immunoreactive varicosity (arrow), and two D D C negative varicosities lying near smooth muscle cells in the wall of an efferent arteriole (E). x 22000. c A single DDC-immunoreactive varicosity lying at a distance of 250 nrn from a distal tubule (D). Only basal lamina separates the varicosity from the tubule, x 44000. d Two DDC-positive axons (arrows) running in the same bundle of axons as a number of DDC-negative axons, x 44000. Bar = 0.5 gm

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functional investigations (Takeuchi et al. 1971 ; Zambraski et al. 1978) have provided no support for the presence of renal sympathetic cholinergic fibres. In this study, by use of the chromaffin reaction combined with immunostaining for TH, all fibres in the dog renal cortex were identified as catecholaminergic axons. Although heavy acetylcholinesterase staining is assumed to be indicative of a functional cholinergic synapse, low levels of acetylcholinesterase activity have also been identified in catecholaminergic nerves (Silver 1974). Barajas and co-workers (Barajas and Wang 1975; Mfiller and Barajas 1972) found that acetylcholinesterase activity in the rat and monkey renal cortex is present within catecholaminergic fibres. The results of the present study, and the existing functional evidence, suggest that the situation is likely to be the same in the dog kidney.

An autonomic neuroeffector junction is generally recog- nized as being characterized by the presence in the axon varicosity of numerous synaptic vesicles, and the absence of interposing tissue elements between axon and effector cell (Bennett 1972; Luff et al. 1987). In this study, the distance between the axon varicosities and the intrarenal structures with which they were associated (vascular smooth muscle cells, juxtaglomerular cells and tubules) varied from 80 to 500 nm. In some cases, only material of basal laminae separated the profile from the effector cell. Similar close relationships have been previously reported between axon varicosities and vascular smooth muscle cells (Devine and Simpson 1968; Bell 1969; Barajas 1978; Luff et al. 1987) and between axon varicosities and tubular epithelial cells (Barajas 1978). A close association (< 100 nm) between vascular smooth muscle cells and axon varicosities supports the view that neuromuscular transmission involves the release of neurotransmitter onto localized subjunctional receptors, rather than the transmitter diffusing to receptors spread widely over the surface of the smooth muscle cell membrane (Luff et al. 1987). In our study, the majority of varicose profiles seen were 150 nm to 200 nm away from the nearest effector cell, rather than the 100 nm or less away as observed by Luff et al. (1987). Although closer neuromuscular and neurotubular associations may be seen more frequently if the axons were serially sectioned, it is unlikely on geometrical grounds that all of the profiles would establish these close associations. It also seems likely that the varicosities with a wider ( > 100 nm) neuromuscular or neurotubular gap represent sites of functional transmitter release, as they always contained numerous synaptic vesicles and were usually bare of Schwann cell on the surface directly apposed to the target cell. Nevertheless, evidence exists suggesting that transmitter action may be restricted to subsynaptic receptors even with neuroeffector gaps of this order (Bell 1969).

We have demonstrated that most catecholaminergic axons in the dog renal cortex are DDC-negative, but that some contain high levels of DDC-immunoreactivity. In the brain, the terminal regions of dopaminergic and noradrenergic neurons can be distinguished by the levels of DDC- immunoreactivity present (H6kfelt et al. 1975; Jaeger et al. 1984). The terminals of noradrenergic axons exhibit immunoreactivity only for TH, while dopaminergic terminals are immunoreactive for both TH and DDC. This probably re- flects a greater dependence of transmitter synthesis in dopaminergic axon terminals on uptake and metabolism of cir- culating 1-DOPA (Bell et al. 1987).

As noradrenergic cell bodies contain high concentra-

tions of DDC, it is possible that considerable amounts of enzyme might also exist in the terminal regions of a noradrenergic neuron with a very short axon. To resolve this question a recent investigation determined the pattern of immunohistochemical staining for DDC in the dog vas deferens, which is supplied entirely by neurons with short axons (Bell et al. 1987). The axons supplying the vas deferens muscle were all DDC negative, indicating that DDC- immunoreactivity is not characteristic of noradrenergic neurons with either long or short axons. The DDC-positive axons observed in the present study are therefore likely to represent dopaminergic nerves.

From the results of this investigation it appears that, in the dog, dopaminergic nerves comprise 20% to 25% of the renal sympathetic supply to both renal vessels and tubules. If it is assumed that renal noradrenergic neurons contain the same amounts of dopamine as do other noradrenergic cells of the same species, then the relative tissue levels of dopamine and noradrenaline in dog renal cortex can be used to calculate the relative numbers of dopaminergic and noradrenergic axons likely to be present. On this basis, the available biochemical data suggest that dopaminergic axons constitute between 5% and 19% of the total renal sympathetic supply (5%: Dinerstein et al. 1983; 10%: Bradley and Hjemdahl 1984; 12-19%: Bell etal. 1978). Retrograde transport of horseradish peroxidase from the sectioned ends of the lateral renal nerves labels around 1000 ganglion cells in the dog paravertebral chain. Making allow- ance for the nerve filaments not labelled, the total renal neuronal pool is likely to be 2000 to 3000 cells (Bell and McLachlan 1982). A quantitative study of the paravertebral ganglia of the dog that contribute to the renal innervation indicated that 450 of these cells exhibited a catecholamine synthetic enzyme profile characteristic of dopaminergic neurons (Muller et al. 1984). Together, these data suggest that dopaminergic neurons contribute approximately 450/200(~3000, or 15% to 20% of the total renal nerve supply. Thus, the size of the axon population found in the present study is similar to the values obtained by a variety of other techniques.

It is well established that noradrenergic nerves have an important influence on renal function (DiBona 1982), and this view is consistent with the present finding of TH-immunoreactive axons associated with renal vessels, juxtaglomerular cells and tubules. However, results from a number of investigations indicate that dopamine may also be involved in the regulation of renal function. Intrarenal infusion of dopamine increases sodium excretion and renal blood flow without causing any systemic haemodynamic changes (Goldberg 1972). Dopamine antagonists inhibit the natriuretic response induced by dopamine infusion and salt loading (Frederickson et al. 1985; McClanahan et al. 1985), suggesting that dopamine released in the kidney may mediate the natriuretic response. Although the natriuresis observed could be explained by renal vasodilation or increased glomerular filtration rate, McGiff and Burns (1967) abolished the natriuretic response to dopamine even though renal blood flow increased by administering phentolamine. Fur- thermore, Boren et al. (1980) found renal dopamine pro- duction and sodium excretion increased in saline-expanded dogs without an increase in renal blood flow or glomerular filtration rate. The close contacts made between the DDC- immunoreactive profiles and renal tubules observed in the present study support the view that dopaminergic nerves

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exert a direct effect on the tubules to increase sodium excretion, as well as modulat ing renal vascular resistance. Al- though dopaminergic axons constituted a slightly smaller percentage of the total sympathetic innervat ion of tubules than of juxtaglomerular vessels, this was not sufficient to suggest preferential control of one or the other site.

Intrarenal infusion of dopamine causes an increase in renin secretion and renal blood flow that can be inhibited by administrat ion of the dopamine antagonists haloperidol and sulpiride (Imbs et al. 1975; Mizoguhi et al. 1983), but not by beta-adrenoreceptor antagonists. Furthermore, administrat ion of the selective dopamine agonists apomor- phine and SKF 82526 increases renin release (Imbs et al. 1976; Lee 1986). Renin release from the dog kidney in response to haemorrhage is reduced by blockade of intrarenal dopamine receptors with ergometrine, suggesting reflex ac- t ivation of intrarenal dopaminergic nerves (Bell and Lang 1978). In our study, DDC-posit ive varicosities were often observed lying 150 nm or closer to juxtaglomerular cells, suggesting that dopaminergic nerves have a direct effect on renin release. This view is supported by Mizoguchi et al. (1983), who found that intrarenal infusion of the vasodila- tors papaverine and acetylcholine lowered renal vascular resistance but had no effect on renin release, indicating that the vasodilator action of dopamine alone is not sufficient to produce an increase in renin release. In addition, Imbs and co-workers (1975) found that dopamine increases renin release without any significant alteration in sodium excretion.

Acknowledgements. This work was supported by a grant from the National Health and Medical Research Council of Australia. The authors thank Miss Karen Cosgriff for technical assistance.

References

Alcorn D, Anderson WP, Ryan GB (1986) Morphological changes in the renal maeula densa during natriuresis and diuresis. Renal Physiol 9:335-347

Barajas L, Wang P (1975) Demonstration of acetylcholinesterase activity in the adrenergic nerves of the renal glomerular arterioles. J Ultrastruc Res 53 : 244-253

Barajas L (1978) Innervation of the renal cortex. Fed Proc 37:326-334

Bell C (1969) Fine structural localization of aeetylcholinesterase at a cholinergic vasodilator nerve-arterial smooth muscle synapse. Circ Res 24:61-70

Bell C, Lang WJ (1978) Effect of renal dopamine receptor and fl-adrenoreceptor blockade on rises in blood angiotensin after haemorrhage, renal ischaemia and frusemide diuresis in the dog. Clin Sci Mol Med 54:17-23

Bell C, Lang WJ, Laska F (1978) Dopamine-containing vasomotor nerves in the dog kidney. J Neurochem 31:77-83

Bell C, Mann R, Borri Voltattorni C (1987) Dopa decarboxylase immunoreactivity in sympathetic nerves of dog vas deferens. Neurosci Lett 81 : 19-23

Bennett MR (1972) Autonomic Neuromuscular Transmission. Cambridge University Press, London

Bennett T, Burnstock G, Cobb JCS, Malmfors T (1970) An ultrastructural histochemical study of the short-term effects of 6- hydroxydopamine on adrenergic nerves in the domestic fowl. Br J Pharmacol 38 : 802 809

Bloom FE (1970) The fine structural localization of biogenic mono- amines in nervous tissue. Int Rev Neurobiol 13:27-66

Boren KR, Henry DP, Selkurt EE, Weinberg WW (1980) Renal modulation of urinary catecholamine excretion during volume expansion in the dog. Hypertension 2: 383-389

Bradley T, Hjemdahl P (1984) Further studies on the renal nerve stimulation induced release of noradrenaline and dopamine from the canine kidney in situ. Acta Physiol Scand 122:369-379

Devine CE, Simpson FO (1968) The morphological basis for the sympathetic control of blood vessels. NZ Med J 67 : 326-334

DiBona GF (1977) Neurogenic regulation of renal tubular sodium reabsorption. Am J Physiol 233:F37-F81

DiBona GF (1982) The functions of the renal nerves. Rev Physiol Biochem Pharmacol 94:75-181

Dinerstein RJ, Jones RT, Goldberg LI (1983) Evidence for dopamine-containing renal nerves. Fed Proc 42: 3005-3008

Dole~el S, Edvinson L, Owman Ch, Owman T (1976) Fluorescence histochemistry and autoradiography of adrenergic nerves in the renal juxtaglomerular complex of mammals and man with spe- cial regard to the efferent arteriole. Cell Tissue Res 169:211-220

Ferguson M, Bell C (1986) Substance P-immunoreactive nerves in the rat kidney. Neurosci Lett 60:183-188

Ferguson M, Ryan GB, Bell C (1986) Localization of sympathetic and sensory neurons innervating the rat kidney. J Auton Nerv Syst 16:279-288

Frederickson ED, Bradley T, Goldberg LI (1985) Blockade of renal effects of dopamine in the dog by the DA1 antagonist SCH 23390. Am J Physiol 249:F236-F240

Goldberg LI (1972) Cardiovascular and renal actions of dopamine : potential clinical applications. Pharmacol Rev 24:1-29

Goormaghtigh N (1939) Existence of an endocrine gland in the media of the renal arterioles. Proc Soc Exp Biol Med 42: 688-689

Harris T, Muller B, Cotton RGH, Borri Voltattorni C, Bell C (1986) Dopaminergic and noradrenergic sympathetic nerves of the dog have different dopa decarboxylase activities. Neurosci Lett 65:155-160

H6kfelt T, Fuxe K, Goldstein M (1975) Applications of immunohistochemistry to studies on monoamine cell systems with spe- cial reference to nervous tissues. Ann NY Acad Sci 254:407-432

Imbs JL, Schmidt M, Schwartz J (1975) Effect of dopamine on renin secretion in the anaesthetized dog. Eur J Pharmacol 33:151-157

Imbs JL, Schmidt M, Velly J, Schwartz J (1976) Effect of apomor- phine and of pimozide on renin secretion in the anesthetized dog. Eur J Pharmacol 38 : 175-178

Jaeger CB, Ruggiero DA, Albert VR, Park DH, Joh TH, Reis DJ (1984) Aromatic L-amino acid decarboxylase in the rat brain: immunocytochemical localization in the neurons of the brain stem. Neuroscience 11:691-713

Joh TH, Ross ME (1983) Preparation of catecholamine-synthesizing enzymes as immunogens for immunohistochemistry. In: Cuello AC (ed) Immunohistochemistry. Wiley-Interscience, New York, pp 121-138

Jonsson G, Sachs C (1970) Effects of 6-hydroxydopamine on the uptake and storage of noradrenaline in sympathetic adrenergic neurons. Eur J Pharm 9 : 141-155

Lee MR (1986) Dopamine and the kidney. In: Lote (ed) Advances In Renal Physiology. Croom Helm, London Sydney, pp 218-246

Ljungquist A, Whgermark J (1970) The adrenergic innervation of intrarenal glomerular and extraglomerular circulatory routes. Nephron 7 : 218-229

Luff S, McLachlan EM, Hirst GDS (1987) An ultrastructural anal- ysis of the sympathetic neuromuscular junctions on arterioles of the submucosa of the guinea pig ileum. J Comp Neurol 257 : 578-594

McClanahan M, Sowers JR, Beck FWJ, Mohanty PK, McKenzie T (1985) Dopaminergic regulation of natriuretic response to acute volume expansion in dogs. Clin Sci 68:263-269

McGiff JC, Burns CR (1967) Separation of dopamine natriuresis from vasodilation: evidence for dopamine receptors. J Lab Clin Med 70: 892

McKenna OC, Angelakos ET (1968a) Adrenergic innervation of the canine kidney. Circ Res 22:345-354

546

McKenna OC, Angelakos ET (1968b) Acetylcholinesterase-containing nerve fibres in the canine kidney. Circ Res 23:645-651

Mizoguchi H, Dzau V J, Siwek LG, Barger C (1983) Effect ofintra- renal administration of dopamine on renin release in conscious dogs. Am J Physiol 244:H39-H45

Miiller J, Barajas L (1972) Electron microscopic and histochemical evidence for a tubular innervation in the renal cortex of the monkey. J Ultrastruct Res 41 : 533-549

Muller BD, Harris T, Borri Voltattorni C, Bell C (1984) Distribu- tion of neurones containing dopa decarboxylase and dopamine- ~-hydroxylase in some sympathetic ganglia of the dog: a quantitative study. Neuroscience 11 : 733-740

Price J, Mudge AW (1983) A subpopulation of rat dorsal root ganglion neurons is catecholaminergic. Nature 304:241-243

Silver A (1974) The Biology of Cholinesterases. North-Holland Publishing, Amsterdam, pp 303-355

Takeuchi J, Aoki S, Nomura G, Mizumura Y, Shimizu H, Kubo T (1971) Nervous control of renal circulation - on the existence of sympathetic cholinergic fibers. J Appl Physiol 31:686-692

Tranzer JP, Richards JG (1975) Ultrastructural cytochemistry of biogenic amines in nervous tissue : methodologic improvements. J Histochem Cytochem 24:1178-1193

Weitson HA, Norvell JE (1969) Cholinergic innervation of the autotransplanted canine kidney. Circ Res 251:535-541

Zambraski EJ, Prosnitz EH, DiBona GF (1976) Lack of evidence for renal vasodilation in anaesthetized dogs. Proc Soc Exp Biol Med 158:462-465

Accepted February 18, 1988

The innervation of the renal cortex in the dog

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