Biomedical subjects

G Jenkin

Publications and source records attributed to G Jenkin.

At least 19 recordsLinked to original sources

PubMed2005

Effects of age and pregnancy on the circulatory activin response of sheep to acute inflammatory challenge by lipopolysaccharide.

The release of activin A in response to intravenous injection of the bacterial cell-wall component lipopolysaccharide (LPS) was investigated in an ovine model of acute inflammatory challenge in newborn and adult sheep, and in non-pregnant and pregnant ewes. Neonatal lambs (<20 days of age) showed a quantitatively similar response in terms of circulating concentrations of activin A, its binding protein follistatin and the cytokine interleukin-6 compared with adult ewes challenged with an equivalent dose (300 ng/kg bodyweight) of LPS. The fever response and plasma tumour necrosis factor-alpha release in response to LPS, however, were significantly (P < 0.01) less in lambs than in the adult group. Pregnant ewes in the last trimester of gestation had similar responses to LPS, in all aspects measured, compared with their non-pregnant counterparts, apart from an ablated fever response. Although the adult and neonatal sheep responded to LPS, a similar response was not apparent in the fetal circulation, possibly due to a protective effect of the placenta. A 10-fold increase in the dose of LPS (from 300 ng to 3 microg/kg bodyweight) given to neonatal lambs elicited an increase in several cytokine responses measured, with a significant (P< 0.05) increase in follistatin release. In contrast, the amount of activin released by the increased dose of LPS was similar to that invoked by the lower dose. The effect of tolerance to LPS was investigated by giving a second challenge of LPS 5 days after the initial injection. In all animals studied, there was an ablated (P < 0.05) response to the subsequent LPS injection, apart from a similar temperature-response profile. These data provide further evidence that activin A concentrations in the bloodstream are acutely responsive to inflammatory challenge in post-natal life and suggest that the response forms a significant component of the innate immune system.

Activins↗

PubMed2004

Mechanisms responsible for parturition; the use of experimental models.

In this review, our knowledge, gleaned from a range of species, of what determines gestation length, how fetal maturation and birth are synchronized and how the uterotonic mechanisms are activated at birth are discussed. Accumulated data indicate that fetal glucocorticoids are involved in, but do not necessarily play a causative role in, the initiation of parturition in eutherian mammals generally. Present observations are consistent with a complex, positive regulatory interaction between estrogens, prostaglandins and oxytocin and are consistent with a role for prostaglandins as the final, common effector in myometrial activation. We are, however, left with the possibility that the initial mechanism for the timing of birth is encoded in the fetal genome and is closely linked to, and activated when, certain prerequisite developmental events have occurred in the fetus. Our understanding of these events in the sheep have led to its extensive use as an experimental model for the study of human clinical correlates of fetal maturation and development and the control of the initiation of parturition.

Animals↗

PubMed2004

Effect of graded hypoxia on activin A, prostaglandin E2 and cortisol levels in the late-pregnant sheep.

The aim of the present study was to determine whether activin A concentrations are dependent on feto-placental oxygen availability and to investigate the temporal relationship of activin A with prostaglandin (PG) E(2) and cortisol. Nine fetal sheep (six hypoxic and three control) were instrumented and catheterised at 0.8 gestation. Reduced uterine blood flow was used to achieve three levels of hypoxia (mild = fetal SaO(2) 40-50%; moderate = fetal SaO(2) 30-40%; severe = fetal SaO(2) 20-30%), for 4 h on 3 consecutive days. Activin A, PGE(2) and cortisol levels were determined in maternal and fetal blood and amniotic fluid. Moderate and severe hypoxia produced a significant (P < 0.05) increase in fetal plasma activin A concentrations. The amniotic fluid activin A concentrations were 15-fold higher than those in the fetal circulation, but were unchanged by hypoxia. The fetal PGE(2) response reflected the degree of hypoxia over the 3 days, with moderate and severe hypoxia producing a significant (P < 0.05) increase in PGE(2) concentrations. Fetal plasma cortisol concentrations were increased ( P < 0.05) during all levels of hypoxia. Fetal arterial activin A was increased in response to moderate and severe hypoxia, but levels were not maintained over the hypoxic period. The increases in activin A and cortisol concentrations preceded the increase in PGE(2).

Activins↗

PubMed2004

Influence of hormone environment and donor age on cryopreserved common wombat (Vombatus ursinus) ovarian tissue xenografted into nude mice.

Developmentally competent oocytes can be collected from xenografted ovarian tissues; however, optimal xenograft conditions need to be established for this technique to be of use in assisted reproduction. In the present study, common wombat ovarian tissue was xenografted under the kidney capsule of nude mice to clarify the role of recipient gonadal status and donor tissue age on graft establishment, follicle development and oocyte recovery. Eighty-nine per cent of all grafts were recovered; of these, 78% contained growing follicles. In female graft recipients, follicle development to the antral stage occurred earlier in ovariectomised recipients compared with intact graft recipients. Similarly, follicle development occurred earlier in recipients of pouch young ovarian tissue grafts when compared with subadult xenografts. Follicle development proceeded to the antral stage in subadult grafts placed under the kidney capsule of male recipient mice, albeit at a slower rate than subadult grafts placed in female recipients. Oocytes were collected from grafts placed in female and male recipients, but no mature oocytes were observed at the time of collection, nor could these oocytes be matured in vitro. The present study demonstrated that common wombat pouch young tissue xenografted to female recipient mice, and subadult ovarian tissue xenografted to male recipient mice, can develop to the antral stage and can therefore facilitate oocyte collection. However, mature oocytes were not obtained using the current protocol.

Age Factors↗

PubMed2003

In vitro maturation of oocytes from non-stimulated common wombats.

Assisted reproductive techniques, such as in vitro oocyte maturation in conjunction with in vitro fertilisation, may be used as a tool to manipulate reproduction. Using the common wombat as a model for the critically endangered northern hairy-nosed wombat, the present study examined whether oocyte maturation could be achieved under field conditions. At the time of collection, no oocytes were at the metaphase II (MII) stage (0/42). After 60 h culture using the submarine incubation system, 34% of oocytes (24/70) matured to telophase/MII, as indicated by the presence of a polar body. The proportion of oocytes that reached MII was higher for oocytes collected from follicles >2 mm in diameter compared with follicles <2 mm (40% v. 22%, respectively). The presence of cumulus cells alone did not influence the maturation potential. Oocytes without cumulus cells collected from follicles >2 mm in diameter had the highest maturation rate (58%). Maturation was not affected by the reproductive status of the common wombat or a delay of up to 5 h before oocyte collection. In conclusion, the present study demonstrated that oocytes collected from non-stimulated common wombats can mature to MII in culture.

Animals↗

PubMed2003

Fertility of mice following receipt of ovaries slow cooled in dimethyl sulphoxide or ethylene glycol is largely independent of cryopreservation equilibration time and temperature.

Cryopreservation procedures generally depend on both the cryoprotectant used and the equilibration conditions to which the material is exposed. The aim of the present study was to examine the effect of cryoprotectants (dimethyl sulphoxide (DMSO) and ethylene glycol (EG)) and equilibration conditions (0, 30 or 120 min at 0 degrees C or 120 min at room temperature) on the fertility of mice receiving cryopreserved mouse ovaries. The study compared the fertility of cryopreserved Day 14 mouse pup ovaries following grafting to adult recipient mice for 4 months. There was no effect of the cryoprotectant or equilibration condition used on the interval to the first plugging/mating or on the interval to the birth of the first litter, the size of litters, the number of litters produced or the total number of offspring produced. Despite this, when compared with control females (untreated, sham and fresh transplant) the cryopreservation and transplantation procedures delayed fertility. However, the size of litters was equivalent for all cryopreserved and control groups (P > 0.05). The results show that, for the equilibration conditions examined, DMSO and EG are equally efficient cryoprotective agents for mouse ovarian tissue.

Animals↗

PubMed2003

Effect of ovariectomy and graft position on cryopreserved common wombat (Vombatus ursinus) ovarian tissue following xenografting to nude mice.

Ovarian tissue xenografting may be applied to increase the population size of rare or endangered animals. However, optimal grafting conditions, such as graft position and recipient hormonal status, are yet to be established. The present study, using common wombat ovarian tissue, showed that development of xenografted ovarian tissue to the antral follicle stage can be achieved irrespective of graft position. However, increased graft recovery rates and follicle survival were evident after grafting under the kidney capsule compared with grafting to subcutaneous sites. No increase in follicle development was observed after placing grafts both under the kidney capsule and subcutaneously in the one recipient compared with grafts placed under the kidney capsule alone or subcutaneously alone. Removal of the recipient's own ovaries at the time of grafting accelerated graft follicle development, with antral follicles seen by Week 12 after grafting compared with by Week 16 in recipients that retained their own ovaries. More oocytes were collected from xenograft recipients receiving hormonal stimulation before collection compared with non-stimulated recipients. No oocytes were mature (extruded a polar body) at the time of collection or after a subsequent period of in vitro maturation. This is the first study to demonstrate that antral follicle development can occur and oocytes can be collected from xenografted common wombat ovarian tissue.

Animals↗

PubMed2001

Physiological and regulatory roles of activin A in late pregnancy.

Unexplained fetal death in utero in late pregnancy represents an increasing proportion of perinatal deaths. It has been assumed that critical hypoxia is the likely mechanism underlying these losses, but the lack of a physiological marker has hampered both confirmation and prediction which could lead to timely intervention. In this paper, we report studies on hypoxia that we have performed in chronically cannulated late pregnant sheep, complemented by parallel investigations undertaken in human pregnancies. Our initial studies were directed towards determining activin secretion in the fetus and mother during late gestation, and immediately after fetal surgery using a sheep model. This led us to propose that there may be a relationship between hypoxia and activin A, follistatin and prostaglandin (PG) release from the feto-placental unit. Subsequent studies have been directed towards examining this potential relationship in sheep and in humans with compromised pregnancies. As a result of these studies, we have identified a potential mechanism by which activin A may be involved in regulating the response of the fetus to hypoxic insult. Activin A and follistatin concentrations increased in late gestation in ovine maternal plasma and in fetal fluids. Feto-placental hypoxemia or maternal isocapnic hypoxemia, leading to fetal hypoxia, were specific triggers for an acute increase in fetal activin A and follistatin concentrations during late gestation. The source and secretion of activin A, follistatin, and the associated release of PGE(2,) from within the feto-placental unit varied according to the site of the insult. The concomitant secretion of activin A and PGE(2) into the fetal circulation and amniotic fluid during reduced uterine blood flow provides an insight into the physiological regulatory mechanisms that might be involved. Changes observed in maternal activin A concentrations in mid and late gestation in the human may also be associated with fetal compromise. In human pregnancies, elevated activin A concentrations were observed in maternal plasma in mid and late gestation, in association with severe pre-eclampsia and with severe fetal growth restriction, compared to those observed in pregnancies with constitutionally small, healthy fetuses. Activin A was also elevated in maternal and arterial cord plasma in women at term during labour and immediately prior to undergoing emergency Caesarean section for failure to progress. These findings offer exciting new possibilities to gain insights into the mechanisms that underlie the maintenance of fetal wellbeing and provide a rationale for the potential that activin A may prove to be a useful clinical marker of fetal distress.

Activins↗

PubMed2001

Follicular development in cryopreserved Common Wombat ovarian tissue xenografted to Nude rats.

The Northern Hairy-nosed Wombat (Lasiorhinus krefftii) is a highly endangered marsupial species and every possible option for sustaining the species needs to be explored. One important approach may be the development of assisted reproductive technologies in the non-endangered Common Wombat (Vombatus ursinus) and Southern Hairy-nosed Wombat (Lasiorhinus latifrons) for application in breeding the Northern Hairy-nosed Wombat. In this study, it was examined whether cryopreserved Wombat ovarian tissue would develop following xenografting to immunologically deficient rats. Ovarian tissue was collected from Common Wombats (n = 3) and cryopreserved as small cortical pieces. After thawing the cortical pieces were grafted underneath the kidney capsule of Nude rats (n = 16). The grafts were recovered at 2, 4, and 10 weeks after transplantation and their gross and histological appearance investigated. Two weeks after grafting (n = 2), the tissue was revascularized and healthy primordial follicles were present. At week 4 (n = 2), some follicular development was present. At week 10, six rats received human chorionic gonadotrophin (hCG) to trigger follicle and oocyte maturation while another six rats were not given any treatment. The administration of hCG did not induce preovulatory follicles and oocyte maturation although type 5 follicles were present in ovarian tissue collected 10 weeks posttransplantation in both treated and untreated groups. This study demonstrates for the first time that Wombat ovarian tissue can survive and function when grafted into immunocompromized rats and that Wombat ovarian follicles can be recruited to growth and development in an ovarian xenograft. This model system has the potential to produce mature oocytes from endangered species for use in assisted reproductive technologies such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and mature oocytes from non-endangered species for nuclear transfer which may be necessary for the preservation of critically endangered species.

Animals↗

PubMed2001

Cryopreservation of mouse ovarian tissue following prolonged exposure to an Ischemic environment.

In cases in which ovarian tissue is to be cryopreserved for tissue or gene banking it is important to maintain its integrity and viability. This study examined how delays between the death of an animal and the collection/cryopreservation of its ovarian tissue influenced follicle viability. Mouse ovaries were placed in PBS+antibiotic (in vitro) or left within the body (in situ) at room temperature for 0, 3, 6, 12, or 24 h following the death of the donor. These ovaries were cryopreserved at 1 degrees C/min on dry ice or in a -84 degrees C freezer using a passive cooling device or by conventional slow cooling (0.3 degrees C/min). The ovaries were grafted under the kidney capsule of ovariectomized recipient mice and collected 2 weeks later, and the size and number of follicles were determined. Cryopreserved ovarian tissue grafted immediately after the death of the donor contained numerous viable and healthy follicles independent of the cooling procedure (dry ice, 134 +/- 32; -84 degrees C, 165 +/- 54; slow, 214 +/- 55 follicles per half ovary). Tissues stored in vitro before cryopreservation retained viable follicles up to 12 h after death (dry ice, 30 +/- 15; -84 degrees C, 86 +/- 45; slow, 93 +/- 33), whereas tissue left in situ had significantly reduced follicle numbers within 3 h of death (dry ice, 36 +/- 12; -84 degrees C, 19 +/- 6; slow, 28 +/- 7). No significant difference was found between the cooling rates tested, indicating that a passive cooling container which cools at 1 degrees C/min is a suitable alternative to conventional slow cooling. We conclude that ovarian tissues for cryobanking should be cryopreserved as soon as possible after collection or death of the animal to ensure maximal follicular survival.

Animals↗

PubMed2001

Comparison of the effects of in vitro and in situ storage on the viability of mouse ovarian tissue collected after death.

Ovarian tissues, collected or salvaged from endangered species at the time of gonadectomy or following their death, are being transported to genebanks for storage with the assumption that they will (subsequently) yield sufficient numbers of germ cells to help preserve the species. The present study aimed to quantify the impact of delays in collecting and/or processing ovarian tissue on the number of follicles in this tissue that remained normal after grafting. The study compared the viability of ovarian tissue stored in vitro (in phosphate-buffered saline) versus in situ (in the body) either on ice or at room temperature for 0 (non-stored fresh grafts), 3, 6, 12, 24 or 48 h. The conditions of storage had significant effects on the total number of morphologically normal follicles, with significantly more follicles in grafts developing from in vitro-stored tissue than in situ-stored tissue. Storage temperature and duration of storage, but not the storage temperature alone, influenced follicle survival. Tissue that was grafted immediately after collection (0 h) was best, but normal follicles were recovered in grafts stored in vitro (on ice or at room temperature) or in situ (on ice only) for up to 48 h before grafting. The rate of follicle loss over time was very rapid, with approximately 50% fewer follicles in grafts derived from tissue stored for only 3 h compared with non-stored fresh grafts (0 h). The results show that viable ovarian tissue can be salvaged from animals up to 48 h after death; however, in order to best protect the follicle population, the ovaries should be removed from the animal's body as soon as possible.

Animals↗

PubMed2001

Feto-placental hypoxemia regulates the release of fetal activin A and prostaglandin E(2).

The evaluation of the role of critical hypoxia in unexplained fetal death in utero has been hampered by the lack of a physiological marker. Here we report the novel observation that feto-placental hypoxemia is an acute trigger for increased activin secretion from the feto-placental unit in late pregnancy. Hypoxemia was induced in chronically cannulated late pregnant fetal sheep by restricting blood flow through the maternal uterine arteries. Using maternal and fetal blood samples and amniotic fluid obtained via chronically implanted catheters, fetal blood gas parameters, plasma and amniotic fluid concentrations of activin A, prostaglandin (PG) E(2) and PGFM, the circulating metabolite of PGF(2alpha), were determined before, during and after a ten hour period of fetal hypoxemia. Hypoxemia acutely increased activin A and PGE(2) levels in both amniotic fluid and the fetal circulation with values rapidly returning to baseline with normoxemia. PGFM also increased in both compartments with a relatively delayed time frame compared to that of activin A and PGE(2). The increase in activin A and PGE(2) induced by hypoxemia may be a mechanism to regulate feto-placental blood flow during fetal compromise and also offers the possibility that activin A represents a useful marker of feto-placental hypoxemia.

Activins↗

PubMed2000

Gonadotrophin administration can benefit ovarian tissue grafted to the body wall: implications for human ovarian grafting.

Ovarian grafting provides a strategy for clinical infertility treatment and is starting to be used in conjunction with ovarian tissue storage for patients at risk of early ovarian failure. As patients are starting to return for their frozen stored tissue we need to ascertain how to maximise follicle survival when this tissue is grafted back to the patient. For research purposes ovarian tissue is commonly grafted to the kidney capsule as the rich capillary bed at this site favours rapid graft revascularization. This is however not an ideal site for natural conceptions or for the harvest of mature oocytes for in vitro fertilization. While oocytes would be relatively easy to recover from grafts on the abdominal wall or subcutaneous tissue graft revascularization at these sites is slower and evidence indicates that fewer follicles survive. As gonadotropins can upregulate angiogenic growth factors in the ovary this study was designed to test whether the administration of exogenous gonadotropins would increase the number of surviving follicles in grafts placed at less vascularised sites. We showed that exogenous gonadotrophins, given to either the donor or the recipient, could increase the number of developing follicles but the magnitude of this effect was influenced by the timing of the injections relative to the time of grafting.

Abdominal Muscles↗

PubMed2000

Evaluation of the long-term function of cryopreserved ovarian grafts in the mouse, implications for human applications.

Ovarian tissue storage has several potentially very valuable clinical applications, including the management of young female patients that are at risk of premature menopause. Ovarian tissue collection, used alone or in combination with oocyte and embryo cryopreservation, may help these patients safeguard their own future fertility. All available evidence from animal studies indicates that grafting of frozen ovarian tissue should be feasible in the human. This study on the mouse shows that frozen thawed ovarian tissue grafts can restore long term fertility to previously ovariectomised recipients. This, and other available evidence, indicates that ovarian tissue collection and storage, used alone or in combination with oocyte or embryo collection, may help safeguard the fertility of patients at risk of premature menopause.

Animals↗

PubMed2000

Follicular development in transplanted fetal and neonatal mouse ovaries is influenced by the gonadal status of the adult recipient.

OBJECTIVE(S): To investigate the pattern of follicular development in transplanted fetal and neonatal mouse ovaries in the presence or absence of the recipient's own ovaries. DESIGN: Controlled experiment. SETTING: Academic research laboratory, Department of Physiology, Monash University, Clayton, Australia. INTERVENTION(S): Mouse ovaries from 16-day-old fetuses, 3-day-old neonates, and 10-day-old neonates were transplanted under the kidney capsule of adult female mice, which either retained their own ovaries in situ or were bilaterally ovariectomized. MAIN OUTCOME MEASURE(S): Histologic analysis. RESULT(S): By 4 weeks after transplantation, fetal and neonatal ovaries transplanted to ovariectomized recipients displayed a pattern of follicular development similar to that observed in in situ adult mouse ovaries. In contrast, follicular development did not progress beyond the early antral stage in fetal and 3-day-old ovaries transplanted to recipients that retained their in situ ovaries. However, 10-day-old ovaries transplanted to recipients that retained their in situ ovaries displayed full follicular development and corpora lutea formation by 8 weeks after transplantation. CONCLUSION(S): Follicular development in transplanted immature ovarian tissue is influenced by the age of the donor ovary and gonadal status of the recipient. (Fertil Steril(R) 2000;74:000-00. Copyright2000 by American Society for Reproductive Medicine.)

Age Factors↗

PubMed2000

Inhibition of premature labor in sheep by a combined treatment of nimesulide, a prostaglandin synthase type 2 inhibitor, and atosiban, an oxytocin receptor antagonist.

OBJECTIVE: The aim of this study was to compare the effects of the selective prostaglandin synthase type 2 inhibitor nimesulide, alone or in combination with the oxytocin receptor antagonist atosiban, on the progression of glucocorticoid-induced premature labor in sheep. Effects on circulating maternal and fetal prostaglandin concentrations and on fetal well-being were also examined. STUDY DESIGN: Premature labor was induced in ewes with long-term catheterized fetuses by infusion of dexamethasone (1 mg/d) starting at 138 +/- 1 days' gestation. Ewes also received an infusion of either nimesulide and atosiban (20.0 and 4.12 mg/kg per day, respectively; n = 5), nimesulide alone (20.0 mg/kg per day; n = 5), or vehicle only (n = 9). Plasma 13,14-dihydro-15-keto-prostaglandin F(2)(alpha) and prostaglandin E(2) concentrations were measured before and during infusions in plasma samples obtained from the maternal and fetal carotid arteries and the utero-ovarian vein. RESULTS: No fetuses from ewes treated with nimesulide and atosiban were delivered during treatment. These animals were killed electively 98.0 +/- 6.8 hours after the commencement of dexamethasone induction. This was significantly longer than the delivery times for those ewes treated with nimesulide alone (71.2 +/- 3.9 hours; n = 5) and for vehicle-treated ewes (51.4 +/- 1.7 hours; n = 9). Both maternal and fetal plasma 13, 14-dihydro-15-keto-prostaglandin F(2alpha) and prostaglandin E(2) concentrations in nimesulide and atosiban-treated ewes and in nimesulide-treated ewes decreased during treatment. In contrast, vehicle-treated ewes showed a significant increase in maternal and fetal plasma 13,14-dihydro-15-keto-prostaglandin F(2alpha) and prostaglandin E(2) concentrations during dexamethasone induction. Uterine electromyographic activity observed in nimesulide and atosiban-treated ewes was significantly suppressed with respect to activities in both vehicle- and nimesulide-treated ewes during the treatment period. All fetuses were alive at delivery or scheduled death. CONCLUSIONS: These results indicate that the combination of an inhibitor of prostaglandin endoperoxidase H synthase type 2 with an oxytocin receptor antagonist is more effective in inhibition of preterm labor than is treatment with a prostaglandin endoperoxidase H synthase type 2 inhibitor alone. The clinical use of atosiban to prevent the oxytocin-stimulated increase in uterine activity associated with labor in combination with nimesulide may permit reduction of the dose of nimesulide used to a level that has minimal impact on fetal well-being.

Animals↗

PubMed1999

Co-localization of Rab3B and oxytocin to electron dense granules of the sheep corpus luteum during the estrous cycle.

Oxytocin and its carrier protein, neurophysin, are both associated with luteal secretory granules which migrate from the paranuclear region to the cell membrane where exocytosis takes place. Rab3 proteins are thought to be associated with membrane vesicles or granules undergoing exocytotic fusion with the plasma membrane. The objective of this study was to determine whether Rab3B is co-localized with oxytocin within the same secretory granules of large luteal cells obtained from corpora lutea of 16 Merino cross ewes at day 3, 7, 12 or 15 of the estrous cycle using immunocytochemistry. The mean granule density (granules/microm3) was not significantly different (P > 0.05) between the days examined. Electron microscopic immunocytochemistry showed that oxytocin and Rab3B were co-localized to the secretory granules on all days evaluated. Rab3B immunostaining was primarily located within secretory granules scattered throughout the cytoplasm. The mean intensity of labelling (number of gold particles) for oxytocin per microm2 cytoplasmic luteal tissue was significantly decreased on day 15 compared to those observed on days 3, 7 and 12 of estrous cycle. No significant changes were observed in the mean intensity of the Rab3B label at the different times of the cycle. The present study provides evidence that a member of the subfamily of Rab proteins, Rab3B, is present and co-localized with oxytocin in the same secretory granules of the ovine corpus luteum. These results implicate Rab3B protein directly or indirectly in the hormone secretory pathway of ovarian tissue.

Animals↗

PubMed1999

Effect of nitric oxide synthase inhibition on the uterine vasculature of the late-pregnant ewe.

OBJECTIVES: We studied the role of nitric oxide in the maintenance of uterine vascular tone during pregnancy. STUDY DESIGN: Late-pregnant ewes were instrumented with ultrasonographic flow probes on the left and right main uterine arteries. A catheter was passed retrogradely into 1 uterine artery from a tributary. In 14 animals nitric oxide synthase inhibitor (N omega-nitro-L-arginine methyl ester; L-NAME) was infused at 2 or 20 mg/kg during a 1-minute period into either the main left or right uterine artery. RESULTS: The nitric oxide synthase inhibitor (20 mg/kg), infused into 1 uterine artery, significantly decreased uterine blood flow (P <.001) bilaterally, increased (P <.05) mean arterial pressure, and decreased heart rate (P <.05). The compound (when infused at 2 mg/kg) also significantly (P <.05) decreased uterine blood flow in the artery ipsilateral to, but not contralateral to, the infusion, with no change in mean arterial pressure and a decrease (P <.05) in heart rate. CONCLUSION: During ovine pregnancy, endogenous nitric oxide production contributes to uterine vasodilatation.

Animals↗