Animals native to the hypoxic and cold environment at high altitude provide an excellent opportunity to elucidate the integrative mechanisms underlying the adaptive evolution and plasticity of complex traits. The capacity for aerobic thermogenesis can be a critical determinant of survival for small mammals at high altitude, but the physiological mechanisms underlying the evolution of this performance trait remain unresolved. We examined this issue by comparing high-altitude deer mice ( Peromyscus maniculatus ) with low-altitude deer mice and white-footed mice ( P. leucopus ). Mice were bred in captivity and adults were acclimated to each of four treatments: warm (25°C) normoxia, warm hypoxia (12 kPa O 2 ), cold (5°C) normoxia or cold hypoxia. Acclimation to hypoxia and/or cold increased thermogenic capacity in deer mice, but hypoxia acclimation led to much greater increases in thermogenic capacity in highlanders than in lowlanders. The high thermogenic capacity of highlanders was associated with increases in pulmonary O 2 extraction, arterial O 2 saturation, cardiac output and arterial–venous O 2 difference. Mechanisms underlying the evolution of enhanced thermogenic capacity in highlanders were partially distinct from those underlying the ancestral acclimation responses of lowlanders. Environmental adaptation has thus enhanced phenotypic plasticity and expanded the physiological toolkit for coping with the challenges at high altitude.

Studies of embryonic and hatchling reptiles have revealed marked plasticity in morphology, metabolism, and cardiovascular function following chronic hypoxic incubation. However, the long-term effects of chronic hypoxia have not yet been investigated in these animals. The aim of this study was to determine growth and postprandial O2 consumption (V̇o2), heart rate (fH), and mean arterial pressure (Pm, in kPa) of common snapping turtles (Chelydra serpentina) that were incubated as embryos in chronic hypoxia (10% O2, H10) or normoxia (21% O2, N21). We hypothesized that hypoxic development would modify posthatching body mass, metabolic rate, and cardiovascular physiology in juvenile snapping turtles. Yearling H10 turtles were significantly smaller than yearling N21 turtles, both of which were raised posthatching in normoxic, common garden conditions. Measurement of postprandial cardiovascular parameters and O2 consumption were conducted in size-matched three-year-old H10 and N21 turtles. Both before and 12 h after feeding, H10 turtles had a significantly lower fH compared with N21 turtles. In addition, V̇o2 was significantly elevated in H10 animals compared with N21 animals 12 h after feeding, and peak postprandial V̇o2 occurred earlier in H10 animals. Pm of three-year-old turtles was not affected by feeding or hypoxic embryonic incubation. Our findings demonstrate that physiological impacts of developmental hypoxia on embryonic reptiles continue into juvenile life.

In vertebrates, changes in surface temperature following exposure to an acute stressor are thought to be promising indicators of the physiological stress response that may be captured noninvasively by infrared thermography. However, the efficacy of using stress‐induced changes in surface temperature as indicators of physiological stress‐responsiveness requires: (1) an understanding of how such responses vary across the body, (2) a magnitude of local, stress‐induced thermal responses that is large enough to discriminate and quantify differences among individuals with conventional technologies, and (3) knowledge of how susceptible measurements across different body regions are to systematic error. In birds, temperature of the bare tissues surrounding the eye (the periorbital, or “eye,” region) and covering the bill have each been speculated as possible predictors of stress physiological state. Using the domestic pigeon (Columba livia domestica; n = 9), we show that stress‐induced changes in surface temperature are most pronounced at the bill and that thermal responses at only the bill have sufficient resolution to detect and quantify differences in responsiveness among individuals. More importantly, we show that surface temperature estimates at the eye region experience greater error due to changes in bird orientation than those at the bill. Such error concealed detection of stress‐induced thermal responses at the eye region. Our results highlight that: (1) in some species, bill temperature may serve as a more robust indicator of autonomic stress‐responsiveness than eye region temperature, and (2) future studies should account for spatial orientation of study individuals if inference is to be drawn from infrared thermographic images.

Reduced oxygen availability (hypoxia) is a potent stressor during embryonic development, altering the trajectory of trait maturation and organismal phenotype. We previously documented that chronic embryonic hypoxia has a lasting impact on the metabolic response to feeding in juvenile snapping turtles (Chelydra serpentina). Turtles exposed to hypoxia as embryos [10% O 2 (H10)] exhibited an earlier and increased peak postprandial oxygen consumption rate, compared with control turtles [21% O 2 (N21)]. In the current study, we measured central blood flow patterns to determine whether the elevated postprandial metabolic response in H10 turtles is linked to lasting impacts on convective transport. Five years after hatching, turtles were instrumented to quantify systemic ( _ Q sys ) and pulmonary ( _ Q pul ) blood flows and heart rate ( f H ) before and after a ∼5% body mass meal. In adult N21 and H10 turtles, f H was increased significantly by feeding. Although total stroke volume (V S,tot ) remained at fasted values, this tachycardia contributed to an elevation in total cardiac output ( _ Q tot ). However, there was a postprandial reduction in a net left-right (L-R) shunt in N21 snapping turtles only. Relative to N21 turtles, H10 animals exhibited higher _ Q sys due to increased blood flow through the right systemic outflow vessels of the heart. This effect of hypoxic embryonic development, reducing a net L-R cardiac shunt, may support the increased postprandial metabolic rate we previously reported in H10 turtles, and is further demonstration of adult reptile cardiovascular physiology being programmed by embryonic hypoxia.

Hypoxia at high altitude can constrain metabolism and performance, and can elicit physiological adjustments that are deleterious to health and fitness. Hypoxic pulmonary hypertension is a particularly serious and maladaptive response to chronic hypoxia, which results from vasoconstriction and pathological remodeling of pulmonary arteries, and can lead to pulmonary edema and right ventricle hypertrophy. We investigated whether deer mice (Peromyscus maniculatus) native to high altitude have attenuated this maladaptive response to chronic hypoxia, and whether evolved changes or hypoxia-induced plasticity in pulmonary vasculature might impact ventilation-perfusion (V-Q) matching in chronic hypoxia. Deer mouse populations from both high and low altitudes were born and raised to adulthood in captivity at sea level, and various aspects of lung function were measured before and after exposure to chronic hypoxia (12 kPa O2, simulating the O2 pressure at 4300 m) for 6-8 weeks. In lowlanders, chronic hypoxia increased right ventricle systolic pressure (RVSP) from 14 to 19 mmHg (P = 0.001), in association with thickening of smooth muscle in pulmonary arteries and right ventricle hypertrophy. Chronic hypoxia also impaired V-Q matching in lowlanders (measured at rest using SPECT-CT imaging), as reflected by increased log SD of the perfusion distribution (log SDQ) from 0.55 to 0.86 (P = 0.031). In highlanders, chronic hypoxia had attenuated effects on RVSP and no effects on smooth muscle thickness, right ventricle mass, or V-Q matching. Therefore, evolved changes in lung function help attenuate maladaptive plasticity and contribute to hypoxia tolerance in high-altitude deer mice.

Acute and chronic changes in ambient temperature alter several aspects of reptilian physiology. We investigated the effects of each type of temperature change on reptilian cardiovascular regulation in red-eared slider turtles (Trachemys scripta), a species known to experience marked seasonal changes in ambient temperature. Turtles were instrumented with occlusive catheters in the femoral artery and vein. Following an acclimation period of 10 days at 13 °C (13(1)), cardiovascular responses to adrenaline, and the cardiac limb of the baroreflex were quantified. Ambient temperature was then reduced 1 °C day(-1) until 3 °C was reached (3(1)). Turtles were maintained at this temperature for 1-week before cardiovascular responses were reassessed. Turtles were then gradually (1 °C day(-1)) returned to an ambient temperature of 13 °C, (13(2)). After a 1-week re-acclimation period, cardiovascular responses were again determined. Finally, 1-week post-pharmacological manipulation of turtles in the 13(2) treatment, ambient temperature was reduced to 3 °C over 24 h (3(2)), and cardiovascular responses were again assessed. Temperature reduction from 13(1) to 3(1) decreased mean arterial blood pressure (P(m)) and heart rate (f(H)) by ~38 and ~63%, respectively. Acute temperature reduction, from 13(2) to 3(2), decreased f(H) similarly, ~66%; however, while P(m) decreased ~28%, this was not significantly different than P(m) at 13(2). The adrenaline injections increased f(H) ranging from 90 to 170% at 13 °C which was a greater change than that observed at 3 °C ranging from a 40 to 70% increase. The increase in P m at the lowest dose of adrenaline did not differ across the temperature treatment groups. The operational point (set-point) P(m) of the baroreflex was decreased similarly by both methods of temperature reduction (3(1) or 3(2)). Further, a hypertensive cardiac baroreflex was absent in the majority of the animals studied independent of temperature. Baroreflex gain and normalized gain based on individual estimates of the relationship were decreased by temperature reduction similarly. Collectively, the data suggest that red-eared slider turtles modulate (down-regulate) some cardiovascular control mechanisms during reduced ambient temperature.

Embryonic growth trajectory is a risk factor for chronic metabolic and cardiovascular disorders and influences birth weight along with early post-natal weight gain in humans. Grb10 is a negative regulator of the main pathways driving embryonic growth and knock-out in mammals increases insulin sensitivity and growth trajectory. This study investigates in Danio rerio the long-term cardiometabolic consequences and associated transcriptomic profiles of morpholino induced early life disruption of grb10a expression. The associated transient knockdown of grb10a increased embryonic growth (+7 %) and metabolic rate (+25 %), while decreasing heart rate (−50 %) in early life. Juvenile growth and respiratory rate were also elevated (+30 % and 7-fold increase respectively). This was associated with permanent remodelling of the transcriptional landscape and the dysregulation of multiple growth-related pathways. This study indicates that zebrafish are a suitable model for life-long investigation of the link between early growth and later life disease risk.

Background Complex organismal traits are often the result of multiple interacting genes and sub-organismal phenotypes, but how these interactions shape the evolutionary trajectories of adaptive traits is poorly understood. We examined how functional interactions between cardiorespiratory traits contribute to adaptive increases in the capacity for aerobic thermogenesis (maximal O2 consumption, V̇O2max, during acute cold exposure) in high-altitude deer mice (Peromyscus maniculatus). We crossed highland and lowland deer mice to produce F2 inter-population hybrids, which expressed genetically based variation in hemoglobin (Hb) O2 affinity on a mixed genetic background. We then combined physiological experiments and mathematical modeling of the O2 transport pathway to examine the links between cardiorespiratory traits and V̇O2max. Results Physiological experiments revealed that increases in Hb-O2 affinity of red blood cells improved blood oxygenation in hypoxia but were not associated with an enhancement in V̇O2max. Sensitivity analyses performed using mathematical modeling showed that the influence of Hb-O2 affinity on V̇O2max in hypoxia was contingent on the capacity for O2 diffusion in active tissues. Conclusions These results suggest that increases in Hb-O2 affinity would only have adaptive value in hypoxic conditions if concurrent with or preceded by increases in tissue O2 diffusing capacity. In high-altitude deer mice, the adaptive benefit of increasing Hb-O2 affinity is contingent on the capacity to extract O2 from the blood, which helps resolve controversies about the general role of hemoglobin function in hypoxia tolerance.