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PubMed2004

Primate Retinal Signaling Pathways: Suppressing ON-Pathway Activity in Monkey With Glutamate Analogues Mimics Human CSNB1-NYX Genetic Night Blindness.

Retinal on-pathway dysfunction is implicated in human complete-type congenital stationary night blindness (CSNB1), a Mendelian genetic condition that results from mutations in the NYX gene encoding the protein nyctalopin. We probed cone pathway dysfunction in four human genotyped CSNB1 affected males by electroretinogram (ERG) recordings elicited with photopic sinusoidal and rapid-on/off-ramp flicker stimuli that are reputed to elicit on/off-pathway activity selectively. Results were analyzed in relation to ERG abnormalities created in anesthetized non-human primates by intravitreal application of glutamate analogues that selectively suppress retinal on- or off-pathway bipolar cell activity. 2-amino-4-phosphonobutyric acid (APB), which selectively blocks light responses of on-pathway depolarizing bipolar cells, fully recreated the essential ERG abnormalities found for human CSNB1 under the condition that the off-pathway remained active. Both CSNB1-NYX humans and APB-treated monkey retina lacked the normal amplitude dip and the phase deflection that occurs in the fundamental component near 12 Hz for sinusoidal flicker stimuli. The off-pathway suppressing agent, cis-2,3-piperidine-dicarboxylic acid (PDA), gave results in monkey quite discordant to CSNB1 human for sinusoidal stimulation. The results implicated a specific on-pathway signaling deficiency in CSNB1-NYX males with no evidence of off-pathway involvement. Likewise, rapid-on/off ramping stimuli also indicated that the functional deficit was localized to the on pathway. Analysis of non-human primate retinal responses after drug application demonstrated a complexity to on/off-pathway contributions to ramping on/off ERG responses not previously anticipated. These results support the hypothesis that nyctalopin acts principally or exclusively within the on pathway at the level of depolarizing bipolar cells, and thus human CSNB1-NYX subjects provide an opportunity to probe the primate visual system for consequences of on-pathway deficits.

Adolescent↗
PubMed2005

Object, space, and object-space representations in the primate hippocampus.

A fundamental question about the function of the primate including human hippocampus is whether object as well as allocentric spatial information is represented. Recordings were made from single hippocampal formation neurons while macaques performed an object-place memory task that required the monkeys to learn associations between objects and where they were shown in a room. Some neurons (10%) responded differently to different objects independently of location; other neurons (13%) responded to the spatial view independently of which object was present at the location; and some neurons (12%) responded to a combination of a particular object and the place where it was shown in the room. These results show that there are separate as well as combined representations of objects and their locations in space in the primate hippocampus. This is a property required in an episodic memory system, for which associations between objects and the places where they are seen are prototypical. The results thus provide an important advance by showing that a requirement for a human episodic memory system, separate and combined neuronal representations of objects and where they are seen "out there" in the environment, is present in the primate hippocampus.

Action Potentials↗
PubMed1991

Corticostriatal transformations in the primate somatosensory system. Projections from physiologically mapped body-part representations.

1. The basal ganglia of primates receive somatosensory input carried largely by corticostriatal fibers. To determine whether map-transformations occur in this corticostriatal system, we investigated how electrophysiologically defined regions of the primary somatosensory cortex (SI) project to the striatum in the squirrel monkey (Saimiri sciureus). Receptive fields in the hand, mouth, and foot representations of cortical areas 3a, 3b, and 1 were mapped by multiunit recording; and small volumes of distinguishable anterograde tracers were injected into different body-part representations in single SI areas. 2. Analysis of labeled projections established that at least four types of systematic remapping occur in the primate corticostriatal system. 1) An area of cortex representing a single body part sends fibers that diverge to innervate multiple regions in the putamen, forming branching, patchy fields that are densest in the lateral putamen. The fields do not form elongated cylindrical forms; rather, they are nearly as extended mediolaterally as they are rostrocaudally. 2) Cortical regions representing hand, mouth, and foot send globally somatotopic, nonoverlapping projections to the putamen, but regions with closely related representations (such as those of the thumb and 5th finger in area 3b) send convergent, overlapping corticostriatal projections. The overlap is fairly precise in the caudal putamen, but in the rostral putamen the densest zones of the projections do not overlap. 3) Regions representing homologous body parts in different SI cortical areas send projections that converge in the putamen. This was true of paired projections from areas 3a and 3b, and from areas 3b and 1. Thus corticostriatal inputs representing distinct somatosensory submodalities can project to the same local regions within the striatum. Convergence is not always complete, however: in the rostral putamen of two cases comparing projections from areas 3a and 1, the densest zones of the projections did not overlap. 4) All projections from SI avoid striosomes and innervate discrete zones within the matrix. 3. These experiments demonstrate that the somatosensory representations of the body are reorganized as they are projected from SI to the somatosensory sector of the primate putamen. This remapping suggests that the striatal representation of the body may be functionally distinct from that of each area of SI. The patchy projections may provide a basis for redistribution of somatosensory information to discrete output systems in the basal ganglia. Transformations in the corticostriatal system could thus be designed for modulating different movement-related programs.

Animals↗
PubMed2001

Primate horizontal cell dynamics: an analysis of sensitivity regulation in the outer retina.

The human cone visual system maintains sensitivity over a broad range of illumination, from below 1 troland to 1,000,000 trolands. While the cone photoreceptors themselves are an important locus for sensitivity regulation-or light adaptation-the degree to which they contribute in primates remains unclear. To determine the range of sensitivity regulation in the outer retina, the temporal dynamics, neural gain control, and response range compression were measured in second-order neurons, the H1 horizontal cells, of the macaque retina. Situated at the first synapse in the retina, H1 cells receive input from a large population of cones. Lee et al. have previously shown that sensitivity regulation in H1 cells is both cone type-specific and spatially restricted. The sensitivity regulation seen in H1 cells at moderate illuminances thus takes place before the summation of cone signals in these cells, and the data establish the H1 cell as a convenient locus for analyzing cone signals. In the present study, cone-driven responses of primate H1 cells to temporally modulated sine-wave stimuli and to increment pulses were measured at steady levels of 1-1,000 trolands. The H1 cell gave a modulated response to sine-wave stimuli and hyperpolarized to increment pulses with overshoots at stimulus onset and offset. The temporal amplitude sensitivity function was primarily low-pass in shape, with a small degree of low-frequency roll off and a resonance shoulder near 40 Hz. A model incorporating a cascade of first-order filters together with an underdamped second-order filter could describe both temporal sinusoidal and pulse hyperpolarizations. Amplitude sensitivity was estimated from both pulse and sine-wave data as a function of the steady adaptation level. Sensitivity at low light levels (1 troland) showed a slowing in temporal dynamics, indicating time-dependent sensitivity regulation. Sensitivity was reduced at light levels above approximately 10 trolands, reflecting both response range compression and neural gain control. Thus the outer retina is a major locus for sensitivity regulation in primates.

Animals↗
PubMed2001

Responses to task-irrelevant visual features by primate prefrontal neurons.

The primate brain is equipped with prefrontal circuits for interpreting visual information, but how these circuits deal with competing stimulus-response (S-R) associations remains unknown. Here we show different types of responses to task-irrelevant visual features in three functionally dissociated groups of primate prefrontal neurons. Two Japanese macaques participated in a go/no-go task in which they had to discriminate either the color or the motion direction of a visual target to make a correct manual response. Prior to the experiment, the monkeys had been trained extensively so that they acquired fixed associations between visual features and required responses (e.g., "green = go"; "downward motion = no-go"). In this design, the monkey was confronted with a visual target from which it had to extract relevant information (e.g., color in the color-discrimination condition) while ignoring irrelevant information (e.g., motion direction in the color-discrimination condition). We recorded from 436 task-related prefrontal neurons while the monkey performed the multidimensional go/no-go task: 139 (32%) neurons showed go/no-go discrimination based on color as well as motion direction ("integration cells"); 192 neurons (44%) showed go/no-go discrimination only based on color ("color-feature cells"); and 105 neurons (24%) showed go/no-go discrimination only based on motion direction ("motion-feature cells"). Overall, however, 162 neurons (37%) were influenced by irrelevant information: 53 neurons (38%) among integration cells, 71 neurons (37%) among color-feature cells, and 38 neurons (36%) among motion-feature cells. Across all types of neurons, the response to an irrelevant feature was positively correlated with the response to the same feature when it was relevant, indicating that the influence from irrelevant information is a residual from S-R associations that are relevant in a different context. Temporal and anatomical differences among integration, color-feature and motion-feature cells suggested a sequential mode of information processing in prefrontal cortex, with integration cells situated toward the output of the decision-making process. In these cells, the response to irrelevant information appears as a congruency effect, with better go/no-go discrimination when both the relevant and irrelevant feature are associated with the same response than when they are associated with different responses. This congruency effect could be the result of the combined input from color- and motion-feature cells. Thus these data suggest that irrelevant features lead to partial activation of neurons even toward the output of the decision-making process in primate prefrontal cortex.

Animals↗
PubMed2006

Testicular xenografts: a novel approach to study cytotoxic damage in juvenile primate testis.

The underlying primary damage to the testis caused by chemotherapeutic regimens during childhood is largely unknown. Xenografting of monkey testes was successfully applied in maturation of juvenile testis to the point of complete spermatogenesis. This allows us to manipulate developing primate testis without direct treatment of patients. This new model is validated establishing the effects of cytotoxic treatment in the immature primate testis. Male castrated nude mice received eight s.c. grafts of juvenile monkey testicular tissue and, 28 weeks later, were injected with busulfan (38 mg/kg, i.p.) or vehicle. Graft numbers, size, and histology were examined. Grafts showed pubertal induction of spermatogenesis to the level of pachytene spermatocytes at point of busulfan treatment and further progressed to the level of round spermatids in control samples at 4 weeks. Busulfan treatment caused a statistically significant decrease in the number of seminiferous tubules containing germ cells. Type B spermatogonia and more advanced stages of spermatogenesis were depleted. A statistically significant decrease to pretreatment level was observed in the number of type A pale and centrally located spermatogonia. Busulfan did not affect type A dark spermatogonia. Occasionally, elongating spermatids were detected in busulfan-treated grafts. Observations show that busulfan selectively destroys differentiating spermatogonia whereas some of the spermatocytes present at the moment of cytotoxic insult are able to continue differentiation. Data indicate that xenografting of testicular monkey tissue is a valid approach to detect the busulfan-induced germ cell damage and serves as a powerful experimental tool to study cytotoxic effects in developing primate testis.

Animals↗
PubMed2004

Plasma and cerebrospinal fluid pharmacokinetics of imatinib after administration to nonhuman primates.

PURPOSE: Imatinib mesylate (Gleevec, Glivec, STI571, imatinib) is a potent tyrosine kinase inhibitor approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. The role of imatinib in the treatment of malignant gliomas and other solid tumors is being evaluated. We used a nonhuman primate model that is highly predictive of the cerebrospinal fluid penetration of drugs in humans to study the pharmacokinetics of imatinib in plasma and cerebrospinal fluid (CSF) after i.v. and p.o. administration. EXPERIMENTAL DESIGN: Imatinib, 15 mg/kg i.v. over 30 min (n = 3) or 30 mg/kg p.o. (n = 3), was administered to nonhuman primates. Imatinib was measured in serial samples of plasma and CSF using high-pressure liquid chromatography with UV absorbance or mass spectroscopic detection. Pharmacokinetic parameters were estimated using model-independent methods. RESULTS: Peak plasma imatinib concentrations ranged from 6.4 to 9.5 microM after i.v. dosing and 0.8 to 2.8 microM after p.o. dosing. The mean +/-SD area under the plasma concentration versus time curve was 2480 +/-1340 microM.min and 1191 +/-146 microM.min after i.v. and p.o. dosing, respectively. The terminal half-life was 529 +/-167 min after i.v. dosing and 266 +/-88 min after p.o. dosing. After i.v. dosing the steady state volume of distribution was 5.9 +/-2.8 liter/kg, and the total body clearance was 12 +/-5 ml/min/kg. The mean peak CSF concentration was 0.25 +/-0.07 microM after i.v. dosing and 0.07 +/-0.04 microM after p.o. dosing. The mean CSF:plasma area under the plasma concentration versus time curve ratio for all of the animals was 5% +/-2%. CONCLUSIONS: There is limited penetration of imatinib into the CSF of nonhuman primates after i.v. and p.o. administration.

Administration, Oral↗
PubMed2004

Efficacy and safety evaluation of human reovirus type 3 in immunocompetent animals: racine and nonhuman primates.

PURPOSE: Human reovirus type 3 has been proposed to kill cancer cells with an activated Ras signaling pathway. The purpose of this study was to investigate the efficacy of reovirus in immunocompetent glioma animal models and safety/toxicity in immunocompetent animals, including nonhuman primates. EXPERIMENTAL DESIGN: Racine glioma cells 9L and RG2 were implanted s.c. or intracranially in Fisher 344 rats with or without reovirus antibodies, followed by treatment of reovirus. To study whether reovirus kills contralateral tumors in the brain and to determine viral distribution, we established an in situ dual tumor model followed by reovirus intratumoral inoculation only into the ipsilateral tumor. To evaluate neurotoxicity/safety of reovirus, Cynomolgus monkeys and immunocompetent rats were given intracranially with reovirus, and pathological examination and/or behavioral studies were done. Viral shedding and clinical biochemistry were systematically studied in monkeys. RESULTS: Intratumorally given reovirus significantly suppressed the growth of both s.c. and intracranially tumors and significantly prolonged survival. The presence of reovirus-neutralizing antibodies did not abort the reovirus' antitumor effect. Reovirus inhibited glioma growth intracranially in the ipsilateral but not the contralateral tumors; viral load in ipsilateral tumors was 15 to 330-fold higher than the contralateral tumors. No encephalitis or behavioral abnormalities were found in monkeys and rats given reovirus intracranially. No treatment-related clinical biochemistry changes or diffuse histopathological abnormality were found in monkeys inoculated intracranially with Good Manufacturing Practice prepared reovirus. Microscopic changes were confined to the region of viral inoculation and were dose related, suggesting reovirus intracranially was well tolerated in nonhuman primates. CONCLUSIONS: These data show the efficacy and safety of reovirus when it is used in the treatment of gliomas in immunocompetent hosts. Inoculation of reovirus into the brain of nonhuman primates did not produce significant toxicities.

Animals↗
PubMed1998

The primates of the Baly Bay area, north-western Madagascar.

Primate surveys were conducted in isolated primary west Malagasy decidous forest blocks around Baly Bay, north-western Madagascar. Eight species of primate were found, including Microcebus c.f. myoxinus, Hapalemur griseus occidentalis and Phaner furcifer. Two species were found only in Namoroka Strict Nature Reserve, which may mean that other forest blocks in the area have experienced primate extinctions. The record of M. c.f. myoxinus came from mangrove, the first confirmed record of a lemur from this habitat. The pelage of female Eulemur fulvus rufus was atypical.

Animals↗
PubMedDate not supplied

The evolution of non-maternal care in anthropoid primates: a test of the hypotheses.

The amount of non-maternal care (allocare) found in primates varies greatly from species to species. Our paper examines this variation and focuses on possible reasons why mothers in some anthropoid primate species are prepared to relinquish their infants to other carers whereas others are not. We use data collected from the literature to test a number of hypotheses that attempt to explain the observed variation in non-maternal care. Analyses were carried out using comparative methods that control for the influence of both body size and phylogeny on life-history and ecological variation. The results support previous studies of both primates and other mammals in finding a clear link between the amount of allocare provided and female reproductive rates. Species with high allocare levels grow rapidly post-natally and wean their infants at a younger age (but at the same relative size) than species of the same body size with lower allocare levels. This early weaning allows high allocare species to support higher birth rates than low allocare species but does not result in earlier maturation. Our results, therefore, suggest that mothers allow non-maternal care of their infants in order to increase their own reproductive output. It is not clear whether such a strategy also benefits the infant, as we could find no link between the presence of allocare and early maturation (which would increase the infant's reproductive output) or between allocare levels and infant survival (as measured by vulnerability to infanticide). This suggests that mothers and infants might come into conflict over transfer to other carers, as the benefits to the mother may not be accompanied by benefits to the infant. However, although mothers may benefit from allocare in some circumstances, they will not be expected to allow allocare if the costs are high (e.g. if there is a high risk to the infant).

Altruism↗
PubMedDate not supplied

In utero allotransplantation of fetal hepatocytes in primates.

OBJECTIVE: Because intrauterine transplantation of fetal hepatocytes could become an effective approach for treating severe genetic disorders of the liver, the objective of this study was to demonstrate the feasibility of in utero allotransplantation of fetal hepatocytes in a nonhuman primate model using direct intraparenchymal administration of donor cells. METHODS: Fetal primary hepatocytes were isolated from 3 fetal primates (MACACA MULATTA) at 89-120 days of gestation, and cryopreserved. When a recipient was available, the cells were thawed and transduced by a beta-galactosidase-expressing retrovirus (3 cases) or labelled with a fluorescent dye (4 cases). Hepatocytes were infused directly into the fetal liver under surgical visual control. Engraftment was assessed by surgical liver biopsies taken 8-60 days following transplantation. RESULTS: Six recipients survived until liver biopsy, and 1 died during the surgical procedure. There was no evidence of engraftment in the 3 fetuses that received genetically marked hepatocytes. All 3 monkeys who received 20-25 x 10(6) hepatocytes from an 89-day-old donor labelled with fluorescent dye had positive liver biopsies 8-11 days following intrauterine transplantation. CONCLUSIONS: In utero allotransplantation of fetal hepatocytes is feasible in the nonhuman primate, and direct intraparenchymal administration enables short-term detection of persisting donor hepatocytes.

Animals↗
PubMed2006

Malagasy primate origins: phylogenies, fossils, and biogeographic reconstructions.

The geographic origin of Malagasy primates is a rich source of debate, providing a useful context for understanding effects of differing phylogenetic interpretations upon area of origin reconstructions. This study has evaluated the biogeographic implications of competing primate phylogenies in order to reconstruct the area of origin of Malagasy strepsirhines. The robusticity of biogeographic inference is examined based on sensitivity to tree topology. The results demonstrate extreme vulnerability to both out-group choice and internal tree topology, suggesting caution for area of origin interpretations from phylogenies that exclude fossil taxa. Moreover, even a single taxon can have a powerful effect upon biogeographic interpretations. Perhaps not surprisingly, it is only with greater phylogenetic resolution that a clearer understanding of the biogeographic origins of Malagasy primates will emerge.

Animals↗
PubMed2006

Effect of fasting on cocaine-amphetamine-regulated transcript, neuropeptide Y, and leptin receptor expression in the non-human primate hypothalamus.

Leptin is a cytokine produced by white adipose tissue that circulates in direct proportion to adiposity and is an important signal of energy balance. Leptin inhibits food intake in rodents by inhibiting the orexigenic neuropetides neuropeptide Y (NPY) and agouti regulated peptide (AgRP) and stimulating the anorexigenic neuropeptides alpha-melanocyte-stimulating hormone (alpha-MSH) and cocaine-amphetamine-regulated transcript (CART). In order to extend our understanding of neuroendocrine regulation of appetite in the primate, we determined the effect of a metabolic challenge on CART, NPY, and leptin receptor (Ob-R) messenger ribonucleic acid (mRNA) in the nonhuman primate (NHP) hypothalamus. Ten adult female rhesus monkeys were either maintained on a regular diet or fasted for two days before euthanasia. CART, NPY, and Ob-R mRNA were measured by in situ hybridization histochemistry (ISHH). A 2-day fast decreased CART expression in the ARC, increased NPY gene expression in the supraoptic nucleus (SON) and paraventricular nucleus (PVN), and increased Ob-R expression in the ventromedial nucleus (VMN). This is the first report that fasting inhibits CART expression and stimulates Ob-R expression in monkeys. Increased NPY expression in the SON and PVN, but not the ARC of fasted monkeys also is novel. With some exceptions, our observations are confirmatory of findings in rodent studies. Similarities in the neuroendocrine responses to a metabolic challenge in monkeys and rodents support extending existing hypotheses of neuroendocrine control of energy homeostasis to primates.

Animals↗
PubMed1990

The retinohypothalamic projection and oxidative metabolism in the suprachiasmatic nucleus of primates and tree shrews.

This study compared the patterns of retinal projections and oxidative metabolism in the hypothalamus of squirrel monkeys, Bonnet macaques, and tree shrews. Intraocular injections of horseradish peroxidase in primates demonstrated that retinal terminals were present from the anterior to posterior poles of the suprachiasmatic nucleus (SCN). The terminals were primarily located in the ventral and ventrolateral regions of the SCN. In addition, there was a relatively even density and distribution of retinal terminals between the ipsilateral and contralateral projections. The pattern of oxidative metabolism in the hypothalamus of the primates examined demonstrated that the SCN is highly metabolic relative to the surrounding area, and distinct regions of the SCN exhibit clear differences in metabolism. These distinct metabolic regions may reflect functional subdivisions within the SCN. In addition, elevated metabolism is found along the hypothalamo-optic chiasm border. The retinal projection to the hypothalamus in tree shrews was very different from that of the primates examined. The contralateral retinal projection was very dense, but the ipsilateral retinal projection was very sparse. Retinal terminals were primarily distributed along the lateral border of the SCN. Both the SCN and the region lateral to the SCN exhibited elevated oxidative metabolism relative to the surrounding hypothalamus.

Animals↗
PubMed1989

Gyrification in the cerebral cortex of primates.

The degree of cortical folding in primates has been analyzed using a gyrification index (GI). Correlation analyses of the GI with body weight, brain weight and neopallial volume show that the human data fit the general trend of the nonhuman anthropoids. Bigger primate brains exhibit a higher degree of fissurization, but a taxonomic difference that is independent of brain weight between prosimians and anthropoids has also been observed. In these regressions, anthropoids differed from prosimians by having a larger increase in gyrification for every unit increase in body or brain weight or neopallial volume. A stepwise regression also shows a prosimian-anthropoid difference. The best predictor for convolutedness in anthropoids is neocortical volume, while in prosimians it is brain weight. The GI in catarrhines is correlated with total sulcal length but not number of sulci. This result suggests paleontological studies of total sulcal length can give direct information on the evolution of cortical folding in primates.

Animals↗
PubMed1981

On the question of the ventral intermediate nucleus in primate thalamus. A study of the lesser bushbaby, Galago senegalensis.

Cytoarchitectural and hodological evidence is given which supports the contention that the large-celled, intermediate zone between ventral posterior lateral (VPL) and ventral lateral (VL) nuclei is an independent thalamic nucleus, designated as the ventral intermediate nucleus (Vim), in the thalamic ventral tier of Galago senegalensis. Observation of Nissl-stained sections indicates that Vim contains cells which are larger than those in VL and more scattered in appearance than those in VPL. Fink and Heimer stained brains show that after cord hemisection the spinothalamic degeneration in Vim is sparse in amount and scattered in organization as opposed to the 'bursts' of dense degeneration in VPL. Following cortical injection of horseradish peroxidase, thalamocortical relay cells in Vim are distinct form those in VPL in both size and organization. Consequently, this study corroborates previous results on another primate and suggests that a distinct VPL-VL transitional nucleus, Vim, is present in the ventral tier of the prosimian primate galago senegalensis. The functional significance of Vim and its possible role in the evolution of primate locomotor behavior are discussed.

Animals↗
PubMed1993

A morphological study of the size of the vascular compartment of the carotid body in a non-human primate (Cercopithecus ethiopus), and a comparison with the cat and rat.

The carotid bodies from 5 adult non-human primates (mean body weight 2.9 kg) were perfusion-fixed at normal arterial blood pressure with 3% phosphate-buffered glutaraldehyde. Serial 5-microns sections were cut, stained, and, using an interactive image analysis system, determinations were made of the volumes of the carotid body and of its vascular and extravascular compartments. The total volume of the carotid body was, on average 0.21 mm3, the total vascular volume contributing 9.7%. The small vessels (5-12 microns diameter) comprised 5.4% of the total volume of the carotid body, or about 56% of the vascular compartment; these estimates were similar to values obtained for the cat and rat. The mean small vessel endothelial area, per unit of extravascular volume (which is assumed to consist largely of type 1 and 2 cells) was 61.8 mm-1 in the primate and 69.7 mm-1 in the cat. A value was not available for the rat. Estimates of the carotid body tissue specific blood flow were 31, 61 and 104 ml/min/100 g organ tissue in the primate, cat and rat, respectively. It was emphasised that these values were not to be confused with estimates of carotid body specific blood flow based on values for total organ blood flow and the dissected weight of the organ.

Animals↗
PubMed1986

Regulation of primate angiotensin II receptors during altered sodium intake.

In the rat, angiotensin II receptors of the adrenal glomerulosa and smooth muscle undergo reciprocal regulatory changes that parallel the changes in target cell sensitivity to angiotensin II during altered sodium intake. In primates, the relative importance of angiotensin II receptor regulation during sodium-induced changes in angiotensin II sensitivity is not clear. To evaluate the role of angiotensin II receptor regulation in the primate, we analyzed the changes in angiotensin II receptors of adrenal and bladder membrane-rich particles after 4 to 6 days of high or low sodium intake in the monkey (Macaca fascicularis). Consistent with the decreased pressor response to angiotensin II, smooth muscle angiotensin II receptors were fewer in sodium-restricted monkeys (93 +/- 17 fmol/mg) than in sodium-loaded monkeys (171 +/- 6 fmol/mg). However, in contrast to the rat, changes in zona glomerulosa angiotensin II receptors in monkey adrenal were similar to those in smooth muscle, decreasing with sodium restriction and increasing with sodium loading (344 +/- 64 and 660 +/- 68 fmol/mg, respectively). There was no change in angiotensin II receptor affinity in either smooth muscle or adrenal particles during altered sodium intake. Concomitant with the decrease in adrenal angiotensin II receptors, 18-hydroxylase activity was increased twofold in adrenal mitochondria from sodium-restricted monkeys (74 +/- 8 fmol/mg/min) compared with sodium-loaded animals (28 +/- 11 fmol/mg/min). The increased sensitivity of the primate adrenal to angiotensin II despite a fall in angiotensin II receptors indicates that full activation of steroidogenesis by angiotensin II can be maintained with partial receptor occupancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗