Pygmy Marmoset Exudate Feeding Stimulates Exudate Production.

Exudates are an important renewable resource for many primates. Exudate renewability is based on observations of primates repeatedly depleting exudate sites and measures of exudate trees' daily replenishment rates, but the role of the consumer in the renewal process is unclear. Trees' exudate production may be independent of the consumer, remaining unchanged regardless of depletion frequency, but since trees produce exudates as a physiological response to fungal infection, they may produce more exudates with more frequent depletion. To test these competing hypotheses, we employed a within-subjects experimental design in which we exposed pygmy marmosets' exudate holes to two treatment conditions: collecting exudates after 5 h and collecting exudates every hour for five consecutive hours. To compare production outputs between treatments, we used generalised linear mixed modelling in which log-transformed production data were a function of treatment with exudate holes nested within trees as a random effect. The model indicated that the cumulative production of hourly exudate removal was significantly greater than the amount accumulated after 5 h. Furthermore, the random effect of holes nested within trees had the greatest impact on variation in differences between treatments, but another unknown source also contributed to the observed variation. These results support the hypothesis that consumers partly drive exudate production, and although it is unknown what other factors, such as fungal load and healing trajectory, may influence variation between treatments, we conclude that pygmy marmosets can stimulate exudate production by consuming exudates.

A comparative study of litter size and sex composition in a large dataset of callitrichine monkeys.

In many birds and mammals, the size and sex composition of litters can have important downstream effects for individual offspring. Primates are model organisms for questions of cooperation and conflict, but the factors shaping interactions among same-age siblings have been less-studied in primates because most species bear single young. However, callitrichines (marmosets, tamarins, and lion tamarins) frequently bear litters of two or more, thereby providing the opportunity to ask whether variation in the size and sex composition of litters affects development, survival, and reproduction. To investigate these questions, we compiled a large dataset of nine species of callitrichines (n = 27,080 individuals; Callithrix geoffroyi, Callithrix jacchus, Cebuella pygmaea, Saguinus imperator, Saguinus oedipus, Leontopithecus chrysomelas, Leontopithecus chrysopygus, Leontopithecus rosalia, and Callimico goeldii) from zoo and laboratory populations spanning 80 years (1938-2018). Through this comparative approach, we found several lines of evidence that litter size and sex composition may impact fitness. Singletons have higher survivorship than litter-born peers and they significantly outperform litter-born individuals on two measures of reproductive performance. Further, for some species, individuals born in a mixed-sex litter outperform isosexually-born individuals (i.e., those born in all-male or all-female litters), suggesting that same-sex competition may limit reproductive performance. We also document several interesting demographic trends. All but one species (C. pygmaea) has a male-biased birth sex ratio with higher survivorship from birth to sexual maturity among females (although this was significant in only two species). Isosexual litters occurred at the expected frequency (with one exception: C. pygmaea), unlike other animals, where isosexual litters are typically overrepresented. Taken together, our results indicate a modest negative effect of same-age sibling competition on reproductive output in captive callitrichines. This study also serves to illustrate the value of zoo and laboratory records for biological inquiry.

Human speech reduces pygmy marmoset (Cebuella pygmaea) feeding and resting at a Peruvian tourist site, with louder volumes decreasing visibility.

Although potentially beneficial in terms of raising awareness and conservation funding, tourist visitation of wild primates can have negative impacts on visited groups. Tourism-generated noise is a relatively understudied facet of ecotourism research, and the effects of tourist-generated speech on free-ranging, wild primates has never been explored previously. This study investigates the behavioral responses of 10 groups of pygmy marmosets (Cebuella pygmaea) to human speech. Through the use of an experimental playback study using recorded human speech, we show that pygmy marmosets within the Tamshiyacu-Tahuayo Reserve, Peru, are significantly less visible, and often move completely out of sight after louder playbacks. Although no consistent differences were found in other behaviors with playback duration and volume, playbacks of human speech tended to increase the amount of time individuals were alert and decrease feeding and resting behaviors. Our results demonstrate that human speech can alter the behavior of visited primates, and identifies a decrease in primate visibility within the increasing volume. As all trials in this study took place near a marmoset group's feeding tree, moving out of sight from the visible study area is a particularly energetically costly behavior, and also has a negative effect on visitor enjoyment as it limits the time that they are able to view the target species. This response was not observed (nor was any other consistent behavior change) in control trials where the marmosets were exposed to human presence but not to speech, suggesting that negative tourist impacts can be reduced by encouraging tourists to refrain from speaking in the presence of visited primate groups.

Mother's little helpers: What we know (and don't know) about cooperative infant care in callitrichines.

Since Darwin (), scientists have been puzzled by how behaviors that impose fitness costs on helpers while benefiting their competitors could evolve through natural selection. Hamilton's () theory of inclusive fitness provided an explanation by showing how cooperative behaviors could be adaptive if directed at closely related kin. Recent studies, however, have begun to question whether kin selection is sufficient to explain cooperative behavior in some species (Bergmüller, Johnstone, Russell, & Bshary, ). Many researchers have instead emphasized the importance of direct fitness benefits for helpers in the evolution of cooperative breeding systems. Furthermore, individuals can vary in who, when, and how much they help, and the factors that affect this variation are poorly understood (Cockburn, ; Heinsohn, ). Cooperative breeders thus provide excellent models for the study of evolutionary theories of cooperation and conflict (Cant, ).

Quantification of Myosin Heavy Chain Isoform mRNA Transcripts in the Supraspinatus Muscle of Vertical Clinger Primates.

Vertical clinging is a specialized form of locomotion characteristic of the primate family Callitrichidae. Vertical clinging requires these pronograde primates to maintain a vertical posture, so the protraction of their forelimbs must resist gravity. Since pronograde primates usually move as horizontal quadrupeds, we hypothesized that the supraspinatus muscle of vertical clingers would present specific characteristics related to the functional requirements imposed on the shoulder area by vertical clinging. To test this hypothesis, we quantified by real-time quantitative polymerase chain reaction the mRNA transcripts of myosin heavy chain (MHC) isoforms in the supraspinatus muscle of 15 species of pronograde primates, including vertical clingers. Our results indicate that the supraspinatus of vertical clingers has a specific expression pattern of the MHC isoforms, with a low expression of the transcripts of the slow MHC-I isoform and a high expression of the transcripts of the fast MHC-II isoforms. We conclude that these differences can be related to the particular functional characteristics of the shoulder in vertical clingers, but also to other anatomical adaptations of these primates, such as their small body size.

Complex cooperative breeders: Using infant care costs to explain variability in callitrichine social and reproductive behavior.

The influence of ecology on social behavior and mating strategies is one of the central questions in behavioral ecology and primatology. Callitrichines are New World primates that exhibit high behavioral variability, which is widely acknowledged, but not always systematically researched. Here, I examine the hypothesis that differences in the cost of infant care among genera help explain variation in reproductive traits. I present an integrative approach to generate and evaluate predictions from this hypothesis. I first identify callitrichine traits that vary minimally and traits that are more flexible (e.g., have greater variance or norm of reaction), including the number of males that mate with a breeding female, mechanisms of male reproductive competition, number of natal young retained, and the extent of female reproductive suppression. I outline how these more labile traits should vary along a continuum of infant care costs according to individual reproductive strategies. At one end of the spectrum, I predict that groups with higher infant care costs will show multiple adult males mating and providing infant care, high subordinate female reproductive suppression, few natal individuals delaying dispersal, and increased reproductive output by the dominant female -with opposite predictions under low infant costs. I derive an estimate of the differences in ecological and physiological infant care costs that suggest an order of ascending costs in the wild: Cebuella, Callithrix, Mico, Callimico, Saguinus, and Leontopithecus. I examine the literature on each genus for the most variable traits and evaluate a) where they fall along the continuum of infant care costs according to their reproductive strategies, and b) whether these costs correspond to the ecophysiological estimates of infant care costs. I conclude that infant care costs can provide a unifying explanation for the most variable reproductive traits among callitrichine genera. The approach presented can be used to generate predictions and motivate researchers to unravel complexity in callitrichine social and reproductive behavior.

An investigation of ecological correlates with hand and foot morphology in callitrichid primates.

Studies of primate taxonomy and phylogeny often depend on comparisons of limb dimensions, yet there is little information on how morphology correlates and contributes to foraging strategies and ecology. Callitrichid primates are ideal for comparative studies as they exhibit a range of body size, limb proportions and diet. Many callitrichid species exhibit a high degree of exudativory, and to efficiently exploit these resources, they are assumed to have evolved morphologies that reflect a level of dependence on these resources. We tested assumptions by considering measurements of limb proportion and frictional features of the volar surfaces in preserved specimens of 25 species with relation to published life history and ecological data. The degree of exudativory and utilization of vertical substrates during foraging were found to correlate both with size and with size-corrected foot and hand dimensions. Smaller species, which engage in greater degrees of exudativory, had proportionally longer hands and feet and more curved claw-like tegulae (nails) on their digits to facilitate climbing on vertical substrates. The density of patterned ridges (dermatoglyphs) on the volar surfaces of the hands and feet is higher in more exudativorous genera, suggesting a role in climbing on vertical tree trunks during foraging. Dermatoglyph comparisons suggest that ridges on the soles and palms may facilitate food procurement by enhancing frictional grip during exudate feeding. Volar pad features corroborate taxonomic relationships described from dental morphology.

The Narrow Niche hypothesis: gray squirrels shed new light on primate origins.

Current hypotheses for primate origins propose that nails and primate-like grasping hands and feet were important early adaptations for feeding in fine branches. Comparative research in this area has focused on instances of convergence in extant animals, showing that species with primate-like morphology feed predominantly from terminal branches. Little has been done to test whether animals without primate-like morphology engage in similar behavior. We tested the fine-branch niche hypothesis for primate origins by observing branch use in Eastern gray squirrels, Sciurus carolinensis, a species lacking primate grasping adaptations that has been understudied in the context of primate origins. We hypothesized that because gray squirrels lack primate-like grasping adaptations, they would avoid feeding and foraging in terminal branches. Instantaneous focal animal sampling was used to examine the locomotor and postural behaviors used while feeding and foraging. Our results demonstrate habitual and effective usage of terminal branches by gray squirrels while feeding and foraging, primarily on tree seeds (e.g., oak, maple, and elm). Discriminant function analysis indicates that gray squirrels feed and forage like primates, unlike some other tree squirrel species. Given the absence of primate-like features in gray squirrels, we suggest that although selection for fine-branch foraging may be a necessary condition for primate origins, it is not sufficient. We propose an alternative model of primate origins. The Narrow Niche hypothesis suggests that the primate morphological suite evolved not only from selection pressure for fine branch use, but also from a lack of engagement in other activities.

On the way to systematize habituation: a protocol to minimize the effects of observer presence on wild groups of Leontocebus lagonotus.

Habituation is used in most field research with primates to minimize observer effects on their behavior. Despite its importance, there is little published on the methods used to habituate different taxa of primates or how these methods vary in different habitat types. We assessed changes in behavior and space use of two groups of Leontocebus lagonotus in the Ecuadorian Amazon in order to document this process. Although the subjects had not been studied before, visitors and researchers were more frequently in the home range of Group 1 than of Group 2. We followed both groups for 2 months, collecting behavioral data through scan sampling and recording the use of space (ground, understory, subcanopy, and canopy) and the routes along which we followed the groups. We then divided our data into two equivalent stages, randomized the data for each stage and looked for significant differences using Wilcoxon tests. Our results show a significant decrease in submissive behaviors toward the observer for both groups and a significant increase in resting and foraging for Group 1. In addition, Group 2 used the subcanopy significantly less and the understory more during the second stage. The routes the animals used were significantly longer in the second stage for Group 1, but not for Group 2. We conclude that our methodology is adequate to advance in the habituation of L. lagonotus in less than 2 months and that a group will habituate more quickly if it has had some previous neutral exposure to humans.

New records and modelling the impacts of climate change on the black-tailed marmosets.

Climate change represents an unprecedented threat to global biodiversity and, for many species, gaps in our knowledge of their biology remain acute. Gaps in baseline knowledge, such as confirmed identifications (Linnean shortfalls) and adequate collections (Wallacean shortfalls), need to be minimized with new studies, since this is often critical for effective conservation. Despite the increase in scientific research on primates in the southwest of the Brazilian Amazon, little is known about the species Mico nigriceps (Ferrari & Lopes, 1992) Primates, Platirryni. In the current study, we sought to reduce the extent of the Wallacean shortfall for M. nigriceps, understand whether climate change represents a threat to the distribution of the species, and identify priority areas for its conservation. Accordingly, we provide 121 new records in 14 locations, obtained directly from the field, and five from the literature. Using this, we carried out ecological niche modeling, to better understand how environmental suitability might limit the area occupied by the species. We then projected a distribution for 2070 with the SSP2-4.5 (more optimistic) and SSP5-8.5 (more pessimistic) scenarios. Our data confirmed the geographic distribution of the species as being restricted to headwaters of the Ji-Paraná/Machado river, but with a 400 km extension to the south. Under the modeled climate change scenarios, the area suitable for the species declines by 21% under the most optimistic, and by 27% in the pessimistic, scenario across the projected 50-year period. Although we have expanded the area of known occurrence for this species, we point out that climate change threatens the stability of this newly-discovered population strongly, and that this danger is intensified by deforestation, fire and hunting. We recommend that further studies be carried out to confirm the presence of the species in adjacent areas, those indicated by generated models as being potential environmentally suitable. In addition, we recommend intensifying forest restoration in currently pastured areas, and protection of the areas forming the current and future habitat of this species through such measures as protected area creation.

Factors influencing weight changes in callitrichids at the Bronx Zoo.

Callitrichids are small monkeys with high metabolic rates who appear to be susceptible to spontaneous diseases and possibly to environmental changes creating challenges in maintaining them in captivity. This study investigates whether life events (i.e. medical, social and housing changes) can influence weight. In previous research, body mass has been shown to be correlated with periods of illness, group composition changes and stress. Weights of 56 individual callitrichid monkeys (20 marmosets, 26 tamarins and 11 lion tamarins) at the WCS's Bronx Zoo were examined over approximately 2½ years. Weight fluctuations were scored based on 5%, 10% and 1 standard deviation criteria during periods of medical (illness and injury), social (introductions and separations), housing (movement within or between buildings) events and during periods when no-events occurred. Additionally, weights were examined for 3 months before and after periods of illness to look for trends in weight changes for 47 medical events (14 marmosets, 21 tamarins and 12 lion tamarins). Moreover, in five alloparenting males (four tamarins and one lion tamarin), weights were examined to determine if weight loss occurred after births as observed in earlier studies. The results show that a 5% and 1SD criterion may be too sensitive a criterion. We therefore deemed that a 10% weight loss may be the best criterion. For marmosets, a 10% weight loss occurred in association with all events. For tamarins, weight loss occurred with housing events. In lion tamarins, weight loss was observed with medical events. No significant weight loss was observed in alloparenting males.

The functional correlates of jaw-muscle fiber architecture in tree-gouging and nongouging callitrichid monkeys.

Common (Callithrix jacchus) and pygmy (Cebuella pygmaea) marmosets and cotton-top tamarins (Saguinus oedipus) share broadly similar diets of fruits, insects, and tree exudates. Marmosets, however, differ from tamarins in actively gouging trees with their anterior dentition to elicit tree exudates flow. Tree gouging in common marmosets involves the generation of relatively wide jaw gapes, but not necessarily relatively large bite forces. We compared fiber architecture of the masseter and temporalis muscles in C. jacchus (N = 18), C. pygmaea (N = 5), and S. oedipus (N = 13). We tested the hypothesis that tree-gouging marmosets would exhibit relatively longer fibers and other architectural variables that facilitate muscle stretch. As an architectural trade-off between maximizing muscle excursion/contraction velocity and muscle force, we also tested the hypothesis that marmosets would exhibit relatively less pinnate fibers, smaller physiologic cross-sectional areas (PCSA), and lower priority indices (I) for force. As predicted, marmosets display relatively longer-fibered muscles, a higher ratio of fiber length to muscle mass, and a relatively greater potential excursion of the distal tendon attachments, all of which favor muscle stretch. Marmosets further display relatively smaller PCSAs and other features that reflect a reduced capacity for force generation. The longer fibers and attendant higher contraction velocities likely facilitate the production of relatively wide jaw gapes and the capacity to generate more power from their jaw muscles during gouging. The observed functional trade-off between muscle excursion/contraction velocity and muscle force suggests that primate jaw-muscle architecture reflects evolutionary changes related to jaw movements as one of a number of functional demands imposed on the masticatory apparatus.

Integration of proximate and evolutionary explanation of reproductive strategy: the case of callitrichid primates and implications for human biology.

We offer examples of how proximate and evolutionary forms of argument may inform each other in better understanding reproductive strategy in callitrichid primates, the smallest of the anthropoid primates. In addition, we illustrate how comparative approaches, when applied judiciously, can aid in the formulation of hypotheses regarding even seemingly unique traits within a taxonomic group. In the first example, examination of the nature of genetics in cytokine systems that leads to altered ovulation number in sheep suggests some relatively simple changes could explain both the adaptation of increased ovulation number in marmosets and the subsequent decrease in ovulation number in the closely related species, callimico. In the second example, the role of body size and phylogeny in explaining the role of maternal energy constraints upon gestation and lactation is explored, leading to additional hypotheses regarding these relations in a species that is both small but also in a phylogenetic line selected for slow reproduction. Finally, the role of comparative data in the study of proximate and evolutionary explanations of "unique" human reproductive strategies is discussed.

New insights into the distribution and conservation status of the Golden-White Tassel-Ear Marmoset Mico chrysoleucos (Primates, Callitrichidae).

Among the 13 Mico species recognized by the IUCN Red List of Threatened Species, six are listed as "Data Deficient". The geographic range of most of the Mico species has been estimated from only a few records. We report new localities and the geographic extension of Mico chrysoleucos. In addition, we confirmed the presence of the species in two distinct protected areas. We modeled the habitat suitability of M. chrysoleucos using the maximum entropy method and including new records obtained by the authors in the state of Amazonas, Brazil. From the total area of occurrence calculated for the species, 22.8% is covered by protected areas and indigenous lands. The annual mean deforestation rate estimated between 2000 and 2015 was 2.95%, and the total area deforested by 2015 was 3354 km2 or 8.6% of the total distribution limits of the species. The habitat lost between 2000 and 2015 was 3.2% (1131 km2) of the total potential distribution, while the habitat loss area legally protected was 31 km2, and the habitat loss in settlements was equal to 691 km2. Our results extend the geographic distribution of the species about 100 km farther south, with the Maracanã River being a possible geographic barrier for the species. The significantly low rate of habitat loss inside protected areas and indigenous land, when compared to unprotected areas, points out the importance of these areas to M. chrysoleucos conservation. The species is relatively wide-ranging, legally protected, and resilient to regional anthropic threats. However, the hydroelectric schemes and the improvement of the road system in southern Amazonia pose an imminent threat to the species.

Fecal glucocorticoid metabolite responses to management stressors and social change in four species of callitrichine monkeys.

The use of enzyme immunoassays (EIA) for the non-invasive measurement of glucocorticoids provides a valuable tool for monitoring health and welfare in sensitive species. We validated methods for measuring fecal glucocorticoid metabolites (FGM) using the response to veterinary exams for four species of callitrichine monkeys: golden lion tamarin (Leontopithecus rosalia, n = 7), callimico (Callimico goeldii, n = 2), pied tamarin (Saguinus bicolor, n = 2), and white-fronted marmoset (Callithrix geoffroyi, n = 2). Routine veterinary exams were performed for the golden lion tamarins and callimicos, but exams for the pied tamarins and white-fronted marmosets were prompted by the death of a social partner. Prior to veterinary exams, fecal markers were evaluated to allow collection of individual samples and estimate approximate gut transit times. Based on this assessment, individual markers were fed in the afternoon, and fresh morning fecal samples were collected throughout this study. Following a veterinary exam, FGM increased roughly 3- to 28-fold above baseline in all species. Although FGM for most species returned to baseline concentrations within 24-48 h, the marmosets exhibited a progressive increase in FGM after an exam in response to the death of a breeding female and subsequent hand-rearing of a neonate. Individual differences were noted in the callimicos and tamarins, with higher baseline FGM levels in females vs. males, although small sample size precluded a clear determination of sex differences. To our knowledge, this is the first study to measure FGM in callimicos and white-fronted marmosets and the first to compare FGM across callitrichine species. These findings highlight the broad applicability of this EIA to measure the stress response of callitrichine monkeys. The progressive increase in FGM in the marmosets during hand-rearing of a neonate suggests that care should be taken to minimize this disturbance as much as possible.

Marmosets.

Wahab et al. introduce the marmosets, a group of peculiar New World monkeys.

Re-description and assessment of the taxonomic status of Saguinus fuscicollis cruzlimai Hershkovitz, 1966 (Primates, Callitrichinae).

Cruz Lima's saddle-back tamarin Saguinus fuscicollis cruzlimai Hershkovitz, 1966, was described from a painting by Eládio da Cruz Lima in his book Mammals of Amazonia, Vol. 1, Primates (1945). The painting was of four saddle-back tamarins from the upper Rio Purus, one of them distinct and the inspiration for Hershkovitz to describe it as a new subspecies. Its exact provenance was unknown, however, and the specimen was lost. Surveys in the Purus National Forest in 2011 resulted in sightings of this tamarin along the north bank of the Rio Inauini, a left-bank tributary of the middle Purus, and also on the left bank of the Purus, north and south of the Rio Inauini. It is possible that it extends north as far as the Rio Pauini, and that S. f. primitivus Hershkovitz, 1977, occurs north of the Pauini as far the Rio Tapauá, both also left-bank tributaries of the Purus. Morphometric and molecular genetic analyses and the coloration of the pelage indicate that this tamarin differs from its neighbors sufficiently to be considered a full species. In his doctoral dissertation [2010, Taxonomy, Phylogeny and Distribution of Tamarins (Genus Saguinus Hoffmannsegg, 1807) Georg-August Universität, Göttingen], C. Matauschek found that saddle-back and black-mantle tamarins diverged from the tamarin lineage around 9.2 million years ago; time enough to warrant their classification in a distinct genus. Leontocebus Wagner, 1840, is the first name available. In this article we re-describe Cruz Lima's saddle-back tamarin. We propose a neotype with a precise locality, and make it a full species in the genus Leontocebus.

Developmental changes in luteinizing hormone/human chorionic gonadotropin steroidogenic responsiveness in marmoset granulosa cells: effects of follicle-stimulating hormone and androgens.

Factors regulating LH/hCG responsiveness in primate granulosa cells were examined in the marmoset monkey (Callithrix jacchus). Granulosa cells were isolated and pooled from small antral (0.5-1.0 mm) and large preovulatory (greater than or equal to 2 mm) follicles from mid- to late follicular phase ovaries of cyclic marmosets. The cells from small and large follicles were cultured in serum-free medium for 48 h in the absence or presence of increasing concentrations of hCG (0.1-100 ng/ml) with or without 0.1 microM androgen [testosterone or 5 alpha-dihydrotestosterone (DHT]). Granulosa cells from small follicles were also cultured in the absence or presence of a constant concentration of human FSH (30 ng/ml) with or without androgen for 48 h before exposure to hCG for an additional 48 h. Steroidogenic responsiveness was assessed by measuring progesterone accumulation in culture medium and aromatase activity in washed monolayers. Granulosa cells from large follicles showed dose-dependent increases in both progesterone accumulation and aromatase activity in response to treatment with hCG. In contrast, granulosa cells from small follicles were unresponsive to hCG. However, pretreatment of granulosa cells from small follicles for 48 h with FSH stimulated hCG responsiveness. The effects of both testosterone and DHT on hCG-stimulated aromatase activity and progesterone accumulation by granulosa cells from large preovulatory follicles were inhibitory. Testosterone and DHT also suppressed basal (no hCG) progesterone accumulation in these cells, but had no effect on basal aromatase activity. The effects of androgens on FSH-induced hCG responsiveness in immature granulosa cells were variable. The results show a development-related increase in marmoset granulosa cell responsiveness to LH/hCG and provide evidence that FSH and androgens interact to regulate the onset and expression of this critical event during preovulatory follicular development in the primate ovary.

Monoclonal antibodies against human renin. Blood pressure effects in the marmoset.

The in vivo effects of two anti-human renin monoclonal antibodies with a high binding affinity for primate renin were studied in conscious, volume-depleted marmosets. These antibodies, R-3-17-7 and R-3-36-16, both have high binding activity for renin, but only R-3-36-16 inhibits the enzymatic activity of renin in vitro. In vivo, R-3-17-7 did not affect blood pressure after intravenous injection of doses up to 100 micrograms/kg, although plasma renin activity was partially reduced. In contrast, R-3-36-16 induced a reduction in blood pressure and an inhibition of plasma renin activity at a threshold dose of 3 micrograms/kg. The maximum fall in blood pressure and complete inhibition of plasma renin activity were observed after R-3-36-16, 10 micrograms/kg; these effects persisted for up to 2 hours. Pretreatment with a converting enzyme inhibitor or nephrectomy prevented the hypotensive effects of R-3-36-16. Conversely, pretreatment with R-3-36-16 prevented the hypotensive effects of a converting enzyme inhibitor. These findings indicate that the hypotensive response induced by R-3-36-16 is due entirely to blockade of the renin-angiotensin system. Thus, R-3-36-16 appears to be a specific, potent, and long-acting inhibitor of primate renin. Such monoclonal antibodies provide interesting tools for studying the effects of acute and chronic renin blockade.

Effects of a specific and long-acting renin inhibitor in the marmoset.

Inhibition of renin was induced in conscious marmosets with CGP 29 287, Z-Arg-Arg-Pro-Phe-His-Sta-Ile-His-Lys (Boc)-OMe, a renin inhibitor with a prolonged duration of action. In vitro, CGP 29 287 is a potent inhibitor of primate plasma renin (inhibitory concentration, 50%: human = 1 X 10(-9) M; marmoset = 5 X 10(-9) M) and less potent against dog (2 X 10(-7) M) or rat (3 X 10(-5) M) plasma renin. CGP 29 287 is a weak inhibitor of other aspartic proteases such as porcine pepsin or bovine cathepsin D (inhibitory concentration, 50% = 4 X 10(-5) M). In furosemide-treated marmosets, CGP 29 287 lowered blood pressure and inhibited plasma renin activity during intravenous infusion and after intravenous bolus injection. The duration of action after intravenous injection was dose dependent and ranged from 1 hour after 0.1 mg/kg to more than 3 hours after 10 mg/kg. High doses of CGP 29 287 (100 mg/kg) were active after oral administration. In all experiments a close relation between inhibition of plasma renin activity and reduction of blood pressure was found. A maximum hypotensive response to CGP 29 287 was associated with complete inhibition of plasma renin activity, and the recovery of blood pressure was accompanied by recovery of plasma renin activity. The hypotensive effects of CGP 29 287 were smaller in untreated than in furosemide-treated marmosets. CGP 29 287 had no influence on blood pressure in marmosets after bilateral nephrectomy or after pretreatment with a converting enzyme inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)