Biomedical subjects

S Lee Adamson

Publications and source records attributed to S Lee Adamson.

17 recordsLinked to original sources

PubMed2006

Endothelium-independent flow-induced dilation in the mouse carotid artery.

BACKGROUND: We investigated the locus of flow regulation of vascular tone in carotid arteries of C57 Bl/6 and eNOS(-/-) mice. METHODS: Arterial segments (2-3 mm) were mounted in a perfusion myograph and preconstricted with 1 muM phenylephrine before monitoring flow-induced changes in lumen diameter. RESULTS: Both control and eNOS(-/-) mice demonstrated flow-dependent relaxation. This response was not attenuated by the NO synthase antagonist L-NAME, the cyclooxygenase inhibitor indomethacin, the selective guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), the adenylate cyclase inhibitor Rp-8-Br-cAMPs, integrin-binding RGD peptides, or by removal of the endothelium. Hypoxia, a physiological stimulus known to alter endothelium-dependent flow regulation of vascular tone, also failed to attenuate the observed flow-mediated dilation. CONCLUSIONS: These findings indicate the existence of a previously unidentified endothelium-independent mechanism of flow-induced dilation in the carotid artery. Further investigations to identify the mechanisms that underlie this response may provide novel therapeutic directions in the treatment of disorders characterized by abnormal flow regulation of vascular tone.

Acetylcholine↗

PubMed2006

Cardiovascular function in mice during normal pregnancy and in the absence of endothelial NO synthase.

In humans, the increased cardiovascular demands of pregnancy are met by increases in cardiac output (CO), stroke volume (SV), plasma volume (PV), and cardiac and aortic inner dimensions and a concurrent decrease in arterial pressure that indicates a fall in total peripheral vascular resistance. The mechanisms responsible for these changes are incompletely understood, but NO synthase (NOS) is believed to play a central role. We assessed whether C57Bl/6J (B6) mice show similar changes and whether these changes are altered in mice lacking the gene for endothelial NOS (eNOS). The CO of B6 mice increased 28% by day 9.5 of gestation because of a 25% increase in SV, and increased 48% by day 17.5 because of a 41% increase in SV. The increase in SV at day 17.5 was associated with a 27% increase in PV, a 15% decrease in arterial pressure, and 10% to 15% increases in aortic and left-ventricular inner dimensions. In the absence of eNOS, CO increased 22% by day 9.5 because of increases in SV (14%) and heart rate (9%), but increased no further by day 17.5. SV near term was lower than B6 mice despite similar 26% increases in PV and 14% decreases in arterial pressure in association with blunted left-ventricular chamber enlargement. All reported changes are P<0.05. We conclude that cardiovascular changes during pregnancy are similar in B6 mice and humans. eNOS plays a critical role in increasing stroke volume in late gestation by promoting cardiac remodeling.

Animals↗

PubMed2006

Meloxicam effectively inhibits preterm labor uterine contractions in a chronically catheterized pregnant sheep model: impact on fetal blood flow and fetal-maternal physiologic parameters.

OBJECTIVE: Preterm birth occurs in 5% to 10% of all pregnancies and is associated with considerable neonatal mortality and morbidity. Effective and safe drugs to prevent preterm labor are not currently available. We have hypothesized that the nonsteroidal anti-inflammatory drug meloxicam, a more selective cyclooxygenase-2 inhibitor will successfully inhibit labor but avoid the complications associated with inhibition of cyclooxygenase-1. STUDY DESIGN: Preterm labor was induced in chronically catheterized sheep by RU486 administration. Animals were then randomized to receive maternal infusions of saline (n = 5) or meloxicam (n = 4) for 48 hours or until delivery when the animals were killed and tissues and blood samples collected. RESULTS: Maternal infusion of meloxicam inhibited uterine contractions, increasing contraction duration, and attenuating frequency and amplitude. Saline-treated animals progressed to delivery. Administration of meloxicam was not associated with any change in fetal or maternal blood gas status, osmolality, arterial pressure, heart rate, or fetal blood flows. CONCLUSION: Meloxicam may represent a potentially safe and effective tocolytic agent.

Abortifacient Agents, Steroidal↗

PubMed2006

Developmental changes in hemodynamics of uterine artery, utero- and umbilicoplacental, and vitelline circulations in mouse throughout gestation.

In human pregnancy, abnormal placental hemodynamics likely contribute to the etiology of early-onset preeclampsia and fetal intrauterine growth restriction. The mouse is increasingly being deployed to study normal and abnormal mammalian placental development, yet the placental hemodynamics in normal pregnancy in mice is currently unknown. We used ultrasound biomicroscopy to noninvasively image and record Doppler blood velocity waveforms from the maternal and embryonic placental circulations in mice throughout gestation. In the uterine artery, peak systolic velocity (PSV) increased significantly from 23+/-2 (SE) to 59+/-3 cm/s, and end-diastolic velocity (EDV) increased from 7+/-1 to 28+/-2 cm/s in nonpregnant versus full-term females so that the uterine arterial resistance index (RI) decreased from 0.70+/-0.02 to 0.53+/-0.02. Velocities in the maternal arterial canal in the placenta were low and nearly steady and increased from 0.9+/-0.03 cm/s at embryonic day 10.5 (E10.5) to 2.4+/-0.07 cm/s at E18.5. PSV in the umbilical artery increased steadily from 0.8+/-0.1 cm/s at E8.5 to 15+/-0.6 cm/s at E18.5, whereas PSV in the vitelline artery increased from 0.6+/-0.1 cm/s at E8.5 to 4+/-0.2 cm/s at E13.5 and then remained stable to term. In the umbilical artery, the EDV detection rate was 0% at <or=E14.5 and 94% at E18.5, and the RI decreased from 1 to 0.82+/-0.01 during this interval. We conclude that ultrasound biomicroscopy can be used to monitor placental hemodynamics during pregnancy in mice. These results provide novel information concerning the development of the vitelline and placental circulations in mice and reveal strong similarities in placental hemodynamics between mice and humans.

Animals↗

PubMed2006

High resolution ultrasound-guided microinjection for interventional studies of early embryonic and placental development in vivo in mice.

BACKGROUND: In utero microinjection has proven valuable for exploring the developmental consequences of altering gene expression, and for studying cell lineage or migration during the latter half of embryonic mouse development (from embryonic day 9.5 of gestation (E9.5)). In the current study, we use ultrasound guidance to accurately target microinjections in the conceptus at E6.5-E7.5, which is prior to cardiovascular or placental dependence. This method may be useful for determining the developmental effects of targeted genetic or cellular interventions at critical stages of placentation, gastrulation, axis formation, and neural tube closure. RESULTS: In 40 MHz ultrasound images at E6.5, the ectoplacental cone region and proamniotic cavity could be visualized. The ectoplacental cone region was successfully targeted with 13.8 nL of a fluorescent bead suspension with few or no beads off-target in 51% of concepti microinjected at E6.5 (28/55 injected). Seventy eight percent of the embryos survived 2 to 12 days post injection (93/119), 73% (41/56) survived to term of which 68% (38/56) survived and appeared normal one week after birth. At E7.5, the amniotic and exocoelomic cavities, and ectoplacental cone region were discernable. Our success at targeting with few or no beads off-target was 90% (36/40) for the ectoplacental cone region and 81% (35/43) for the exocoelomic cavity but tended to be less, 68% (34/50), for the smaller amniotic cavity. At E11.5, beads microinjected at E7.5 into the ectoplacental cone region were found in the placental spongiotrophoblast layer, those injected into the exocoelomic cavity were found on the surface or within the placental labyrinth, and those injected into the amniotic cavity were found on the surface or within the embryo. Following microinjection at E7.5, survival one week after birth was 60% (26/43) when the amniotic cavity was the target and 66% (19/29) when the target was the ectoplacental cone region. The survival rate was similar in sham experiments, 54% (33/61), for which procedures were identical but no microinjection was performed, suggesting that surgery and manipulation of the uterus were the main causes of embryonic death. CONCLUSION: Ultrasound-guided microinjection into the ectoplacental cone region at E6.5 or E7.5 and the amniotic cavity at E7.5 was achieved with a 7 day postnatal survival of >/=60%. Target accuracy of these sites and of the exocoelomic cavity at E7.5 was > or =51%. We suggest that this approach may be useful for exploring gene function during early placental and embryonic development.

Amnion↗

PubMed2006

Anatomical phenotyping in the brain and skull of a mutant mouse by magnetic resonance imaging and computed tomography.

Since genetically modified mice have become more common in biomedical research as models of human disease, a need has also grown for efficient and quantitative methods to assess mouse phenotype. One powerful means of phenotyping is characterization of anatomy in mutant vs. normal populations. Anatomical phenotyping requires visualization of structures in situ, quantification of complex shape differences between mouse populations, and detection of subtle or diffuse abnormalities during high-throughput survey work. These aims can be achieved with imaging techniques adapted from clinical radiology, such as magnetic resonance imaging and computed tomography. These imaging technologies provide an excellent nondestructive method for visualization of anatomy in live individuals or specimens. The computer-based analysis of these images then allows thorough anatomical characterizations. We present an automated method for analyzing multiple-image data sets. This method uses image registration to identify corresponding anatomy between control and mutant groups. Within- and between-group shape differences are used to map regions of significantly differing anatomy. These regions are highlighted and represented quantitatively by displacements and volume changes. This methodology is demonstrated for a partially characterized mouse mutation generated by N-ethyl-N-nitrosourea mutagenesis that is a putative model of the human syndrome oculodentodigital dysplasia, caused by point mutations in the gene encoding connexin 43.

Animals↗

PubMed2006

Embryonic and neonatal phenotyping of genetically engineered mice.

Considerable progress has been made in adapting existing and developing new technologies to enable increasingly detailed phenotypic information to be obtained in embryonic and newborn mice. Sophisticated methods for imaging mouse embryos and newborns are available and include ultrasound and magnetic resonance imaging (MRI) for in vivo imaging, and MRI, vascular corrosion casts, micro-computed tomography, and optical projection tomography (OPT) for postmortem imaging. In addition, Doppler and M-mode ultrasound are useful noninvasive tools to monitor cardiac and vascular hemodynamics in vivo in embryos and newborns. The developmental stage of the animals being phenotyped is an important consideration when selecting the appropriate technique for anesthesia or euthanasia and for labeling animals in longitudinal studies. Study design also needs to control for possible differences between inter- and intralitter variability, and for possible long-term developmental effects caused by anesthesia and/or procedures. Noninvasive or minimally invasive intravenous or intracardiac injections or blood sampling, and arterial pressure and electrocardiography (ECG) measurements are feasible in newborns. Whereas microinjection techniques are available for embryos as young as 6.5 days of gestation, further advances are required to enable minimally invasive fluid or tissue samples, or blood pressure or ECG measurements, to be obtained from mouse embryos in utero. The growing repertoire of techniques available for phenotyping mouse embryos and newborns promises to accelerate knowledge gained from studies using genetically engineered mice to understand molecular regulation of morphogenesis and the etiology of congenital diseases.

Animals↗

PubMed2006

Vascular corrosion casting of the uteroplacental and fetoplacental vasculature in mice.

This chapter describes methods for making vascular corrosion casts of the uteroplacental and fetoplacental vasculature of the mouse placenta. A catheter placed in the ascending thoracic aorta of a pregnant mouse permits the introduction of a methyl methacrylate casting compound into the lower body vasculature, including the uterus and placenta. A fine-tipped glass cannula attached to a double-lumen catheter is used to instill the same casting compound in the fetoplacental vessels of mouse placentas. Following polymerization of the casting compound, tissue is digested off of the placental casts using 20% KOH. The washed and dried casts are then available for light or scanning electron microscopy. The methods described have been used to cast the mouse uteroplacental vasculature from 5.5-18.5 d gestation and the fetoplacental vasculature from 12.5 d gestation to term.

Animals↗

PubMed2005

Two mouse mutations mapped to chromosome 11 with differing morphologies but similar progressive inflammatory alopecia.

Alopecia is a common dermatological condition in humans and other mammals. Here, we present two similar but histologically distinct mouse models of scarring alopecia. Both mutant lines were generated using random genome-wide N-ethyl-N-nitrosourea mutagenesis, and both harbor dominant mutations on chromosome 11. In both mutants, there is an early onset of alopecia that progresses to nearly complete pelage hair loss in both males and females by 20 weeks of age. Histologically, there is an increased dermal cellularity due to inflammatory cell infiltration at 7-10 days of age. By 3 weeks of age, the epidermis is acanthotic and the dermis is approximately twice as thick as in control mice due to a substantial, mostly mononuclear, inflammatory cell infiltrate. This infiltrate becomes more perifollicular by 4-5 weeks of age but is localized differently in the two mutants. In alopecia 1 (Alo-1), the perifollicular infiltrate is confined to the portion of the follicle within the dermis, whereas in Alo-2, the infiltrate extends the full length of the follicle. Expression of major histocompatibility complex (MHC) class I on the follicular epithelium in the two mutants is much greater than that in non-mutants. Furthermore, MHC class I expression is localized differently in the two mutant lines and mirrors the pattern of the inflammatory infiltrate. Despite these differences, the clinical progression of alopecia is identical in both mutants. The early onset of the disease, predictable progression, and differences in inflammatory cell localization between the two mutants make these mice particularly useful models for inflammatory hair loss and autoimmune diseases in general.

Alopecia↗

PubMed2005

A Gja1 missense mutation in a mouse model of oculodentodigital dysplasia.

Oculodentodigital dysplasia (ODDD) is an autosomal dominant disorder characterized by pleiotropic developmental anomalies of the limbs, teeth, face and eyes that was shown recently to be caused by mutations in the gap junction protein alpha 1 gene (GJA1), encoding connexin 43 (Cx43). In the course of performing an N-ethyl-N-nitrosourea mutagenesis screen, we identified a dominant mouse mutation that exhibits many classic symptoms of ODDD, including syndactyly, enamel hypoplasia, craniofacial anomalies and cardiac dysfunction. Positional cloning revealed that these mice carry a point mutation in Gja1 leading to the substitution of a highly conserved amino acid (G60S) in Cx43. In vivo and in vitro studies revealed that the mutant Cx43 protein acts in a dominant-negative fashion to disrupt gap junction assembly and function. In addition to the classic features of ODDD, these mutant mice also showed decreased bone mass and mechanical strength, as well as altered hematopoietic stem cell and progenitor populations. Thus, these mice represent an experimental model with which to explore the clinical manifestations of ODDD and to evaluate potential intervention strategies.

Abnormalities, Multiple↗

PubMed2004

Baf60c is essential for function of BAF chromatin remodelling complexes in heart development.

Tissue-specific transcription factors regulate several important aspects of embryonic development. They must function in the context of DNA assembled into the higher-order structure of chromatin. Enzymatic complexes such as the Swi/Snf-like BAF complexes remodel chromatin to allow the transcriptional machinery access to gene regulatory elements. Here we show that Smarcd3, encoding Baf60c, a subunit of the BAF complexes, is expressed specifically in the heart and somites in the early mouse embryo. Smarcd3 silencing by RNA interference in mouse embryos derived from embryonic stem cells causes defects in heart morphogenesis that reflect impaired expansion of the anterior/secondary heart field, and also results in abnormal cardiac and skeletal muscle differentiation. An intermediate reduction in Smarcd3 expression leads to defects in outflow tract remodelling reminiscent of human congenital heart defects. Baf60c overexpressed in cell culture can mediate interactions between cardiac transcription factors and the BAF complex ATPase Brg1, thereby potentiating the activation of target genes. These results reveal tissue-specific and dose-dependent roles for Baf60c in recruiting BAF chromatin remodelling complexes to heart-specific enhancers, providing a novel mechanism to ensure transcriptional regulation during organogenesis.

Animals↗

PubMed2004

The fetal cardiovascular response to antenatal steroids in severe early-onset intrauterine growth restriction.

OBJECTIVE: Our aim was to study the hemodynamic effects of betamethasone on fetuses with intrauterine growth restriction (IUGR) with absent or reversed end-diastolic (ARED) umbilical artery flow. STUDY DESIGN: Color/pulsed Doppler waveforms were obtained before and after intramuscular injections of betamethasone in 19 consecutive fetuses with IUGR/ARED and 6 control fetuses. Peak velocities and pulsatility index (PI) values were obtained from the umbilical (UA) and middle cerebral (MCA) arteries and intrahepatic umbilical vein (UV). RESULTS: Ten ARED fetuses developed transient positive umbilical end-diastolic flow after steroids, whereas nine fetuses showed persistent ARED. The persistent ARED subgroup demonstrated increased UA and UV peak velocities after steroids, which may indicate fetal hypertension. Fetal death (n=2) and severe acidosis (n=2) were confined to the subgroup with persistent ARED. CONCLUSION: Preterm IUGR/ARED fetuses exhibit divergent cardiovascular responses to prenatal steroids. Intensive Doppler-based fetal monitoring may identify a subset of fetuses prone to decompensation after maternal steroid administration.

Acidosis↗

PubMed2004

Developmental changes in integrated ultrasound backscatter from embryonic blood in vivo in mice at high US frequency.

Mouse blood imaged using high-frequency ultrasound (US) is more echogenic in embryos than in adults. Studying changes in blood echogenicity in embryos may be of fundamental interest in studies on the genetic regulation of normal and abnormal blood development in mutant mice. Embryonic red blood cells (RBCs) are large and nucleated in midgestation but decrease in size and become enucleated as they mature. We therefore hypothesised that these structural alterations are responsible for variations in echogenicity of embryonic blood with gestational age and development. The objective of the current study was to quantify these structural changes in echogenicity (echo brightness) and apparent integrated backscatter (AIB) from embryonic blood at high US frequencies in vivo in mice. Results from anaesthetised pregnant mice studied using transcutaneous US showed that echogenicity of embryonic blood in the heart, aorta and umbilical cord and AIB within the heart chambers peaked at embryonic day (ED) 13.5 and then decreased progressively toward term. Between EDs 13.5 and 17.5 (near term), RBC mean cell volume decreased from 133 to 109 fL, haematocrit increased from 12 to 34%, and the percentage of nucleated RBCs decreased from 59 to 2%. Relative to younger ages, RBC nuclei at ED 13.5 were small and dense (pyknotic) which may have contributed to the peak in echogenicity and AIB at this age. To calculate the AIB, radiofrequency (RF) signals with centre frequencies of 28 MHz and 35 MHz were integrated over the 16- to 35-MHz and 21- to 42-MHz frequency range, respectively. At 28 MHz, mean apparent integrated backscatter of blood in the embryonic heart increased significantly from 0.0023 +/- 0.0004 Sr.cm(-1) (mean +/- SEM) at ED 12.5 to peak at 0.0037 +/- 0.0005 Sr.cm(-1) at ED 13.5. The mean AIB then decreased progressively with advancing gestation to 0.0002 +/- 0.0001 Sr.cm(-1) at ED 17.5. At 35 MHz, the mean AIB changed similarly with gestational age, except that values were lower than at 28 MHz at all ages. Higher attenuation of US at 35 MHz than at 28 MHz in tissue likely accounted for the lower AIB of blood insonified at 35 MHz. We speculate that developmental changes in red cell morphology are responsible for the observed changes in echogenicity and AIB of embryonic blood with gestational age in mice.

Animals↗

PubMed2003

Developmental changes in left and right ventricular diastolic filling patterns in mice.

Developmental changes in left and right ventricular diastolic filling patterns were determined noninvasively in isoflurane-anesthetized outbred ICR mice. Blood velocities in the mitral and tricuspid orifices were recorded in 16 embryos at days 14.5 (E14.5) and 17.5 of gestation (E17.5) using an ultrasound biomicroscope and also serially in three groups of postnatal mice aged 1-7 days (n = 23), 1-4 wk (n = 18), and 4-12 wk (n = 27) using 20-MHz pulsed Doppler. Postnatal body weight increased rapidly to 8 wk. Heart rate increased rapidly from approximately 180 beats/min at E14.5 to approximately 380 beats/min at 1 wk after birth and then more gradually to plateau at approximately 450 beats/min after 4 wk. Ventricular filling was quantified using the ratio of peak velocity of early ventricular filling due to active relaxation (E wave) to that of the late ventricular filling caused by atrial contraction (A wave) (peak E/A ratio) and the ratio of the peak E velocity to total time-velocity integral of E and A waves (peak E/total TVI ratio). Both ventricles had similar diastolic filling patterns in embryos (peak E/A ratio of 0.28 +/- 0.02 for mitral flow and 0.27 +/- 0.02 for tricuspid flow at E14.5). After birth, mitral peak E/A increased to >1 between the third and fifth day, continued to increase to 2.25 +/- 0.25 at approximately 3 wk, and then remained stable. The tricuspid peak E/A ratio increased much less but stabilized at the same age (increased to 0.79 +/- 0.03 at 3 wk). The peak E/total TVI ratio showed similar left-right differences and changes with development. Age-related changes were largely due to increases in peak E velocity. The results suggest that diastolic function matures approximately 3 wk postnatally, presumably in association with maturation of ventricular recoil and relaxation mechanisms.

Anesthesia↗

PubMed2002

Interactions between trophoblast cells and the maternal and fetal circulation in the mouse placenta.

Mammalian embryos have an intimate relationship with their mothers, particularly with the placental vasculature from which embryos obtain nutrients essential for growth. It is an interesting vascular bed because maternal vessel number and diameter change dramatically during gestation and, in rodents and primates, the terminal blood space becomes lined by placental trophoblast cells rather than endothelial cells. Molecular genetic studies in mice aimed at identifying potential regulators of these processes have been hampered by lack of understanding of the anatomy of the vascular spaces in the placenta and the general nature of maternal-fetal vascular interactions. To address this problem, we examined the anatomy of the mouse placenta by preparing plastic vascular casts and serial histological sections of implantation sites from embryonic day (E) 10.5 to term. We found that each radial artery carrying maternal blood into the uterus branched into 5-10 dilated spiral arteries located within the metrial triangle, populated by uterine natural killer (uNK) cells, and the decidua basalis. The endothelial-lined spiral arteries converged together at the trophoblast giant cell layer and emptied into a few straight, trophoblast-lined "canals" that carried maternal blood to the base of the placenta. Maternal blood then percolated back through the intervillous space of the labyrinth toward the maternal side of the placenta in a direction that is countercurrent to the direction of the fetal capillary blood flow. Trophoblast cells were found invading the uterus in two patterns. Large cells that expressed the trophoblast giant cell-specific gene Plf (encoding Proliferin) invaded during the early postimplantation period in a pattern tightly associated with spiral arteries. These peri/endovascular trophoblast were detected only approximately 150-300 microm upstream of the main giant cell layer. A second type of widespread interstitial invasion in the decidua basalis by glycogen trophoblast cells was detected after E12.5. These cells did not express Plf, but rather expressed the spongiotrophoblast-specific gene Tpbp. Dilation of the spiral arteries was obvious between E10.5 and E14.5 and was associated with a lack of elastic lamina and smooth muscle cells. These features were apparent even in the metrial triangle, a site far away from the invading trophoblast cells. By contrast, the transition from endothelium-lined artery to trophoblast-lined (hemochorial) blood space was associated with trophoblast giant cells. Moreover, the shaping of the maternal blood spaces within the labyrinth was dependent on chorioallantoic morphogenesis and therefore disrupted in Gcm1 mutants. These studies provide important insights into how the fetoplacental unit interacts with the maternal intrauterine vascular system during pregnancy in mice.

Animals↗

PubMed2002

Experimental angiogenesis of arterial vasa vasorum.

Vasa vasorum are important sources of oxygen and nutrients to vascular tissues and their proliferation influences the pathogenesis of arterial disease; however, the regulation of their growth is poorly understood partly because of a lack of appropriate experimental models. We cuffed common carotid arteries of rabbits with segments of the contralateral carotid artery, a procedure that resulted in rapid and extensive elaboration of adventitial vasa vasorum and connective tissue. Endothelium-lined microvessels were observed at 1 week but vessels as large as 300 microm with an organizing media were common by 3 weeks. These vasa vasorum arose primarily from the vascular supply to contiguous tissues, but also from the carotid artery. This angiogenesis was accompanied by increased expression of the angiogenic factor, vascular endothelial growth factor (VEGF), in the invading connective tissue cells and increased expression of the transcriptional regulator of VEGF, hypoxia-inducible factor-1alpha (HIF-1alpha), in these connective tissues and in the cuffing artery. These findings are consistent with the hypothesis that upregulation of HIF-1alpha and VEGF expression drives angiogenesis of vasa vasorum in this model. This simple model may be amenable to the study of the development and elaboration of vasa vasorum, especially in the context of vascular pathologies.

Animals↗

PubMed2002

Maternal cardiovascular changes during pregnancy and postpartum in mice.

Genetically altered mice may provide useful models for exploring cardiovascular regulation during pregnancy and postpartum if changes in mice mimic humans. We found in awake ICR (CD-1) mice at 17.5 days gestation that hematocrit was reduced 18%, and the pressor response to intravenous angiotensin II was reduced ~33%. Arterial pressure in awake mice was 12% lower in early pregnancy (3.5 days) than late pregnancy (17.5 days) and postpartum (3 and 17 days after delivery), whereas heart rate was 10-20% higher in the peripartum period (17.5 days gestation and 3 days postpartum). In late pregnancy, cardiac output under isoflurane anesthesia was 64% higher than in nonpregnant mice, due to a 37% increase in stroke volume and a 17% increase in heart rate. All changes P < 0.05. We conclude that, as in humans, mice exhibit hypotension in early pregnancy, and a blunted pressor response to angiotensin II, a decrease in hematocrit, and a marked increase in cardiac output in late pregnancy.

Animals↗