Non-pregnant Dogs Research Articles

Pregnancy augments hepatic glucose storage in response to a mixed meal

Studies were carried out on conscious female non-pregnant (NP) and pregnant (P; third-trimester) dogs (n 16; eight animals per group) to define the role of the liver in mixed meal disposition with arteriovenous difference and tracer techniques. Hepatic and hindlimb substrate disposal was assessed for 390 min during and after an intragastric mixed meal infusion labelled with [¹⁴C]glucose. The P dogs exhibited postprandial hyperglycaemia compared with NP dogs (area under the curve (AUC; change from basal over 390 min) of arterial plasma glucose: 86 680 (sem 12 140) and 187 990 (sem 33 990) mg/l in NP and P dogs, respectively; P < 0·05). Plasma insulin concentrations did not differ significantly between the groups (AUC: 88 230 (sem 16 314) and 69 750 (sem 19 512) pmol/l in NP and P dogs, respectively). Net hepatic glucose uptake totalled 3691 (sem 508) v. 5081 (sem 1145) mg/100 g liver in NP and P dogs, respectively (P = 0·38). The AUC of glucose oxidation by the gut and hindlimb were not different in NP and P dogs, but hepatic glucose oxidation (84 (sem 13) v. 206 (sem 30) mg/100 g liver) and glycogen synthesis (0·4 (sem 0·5) v. 26 (sem 0·7) g/100 g liver) were greater in P dogs (P < 0·05). The proportion of hepatic glycogen deposited via the direct pathway did not differ between the groups. Hindlimb glucose uptake and skeletal muscle glycogen synthesis was similar between the groups, although final glycogen concentrations were higher in NP dogs (9·6 (sem 0·6) v. 70 (sem 0·6) mg/g muscle; P < 0·05). Thus, hepatic glucose oxidation and glycogen storage were augmented in late pregnancy. Enhanced hepatic glycogen storage following a meal probably facilitates the maintenance of an adequate glucose supply to maternal and fetal tissues during the post-absorptive period.

The Corpus Luteum of the Dog: Source and Target of Steroid Hormones?

Aim of this paper is to review our present understanding on the endocrine control of luteal function in the bitch and to add some new data generated in our laboratories in support of the hypothesis of a paracrine/autocrine role of corpus luteum (CL) derived steroid hormones. Luteal lifespan in non-pregnant dogs often exceeds that of pregnant dogs, where luteal regression terminates in a rapid luteolysis, immediately prior to parturition. In non-pregnant dogs, luteal regression occurs independently of a uterine luteolysin and in spite of increased gonadotropic support during the last third of dioestrus. The CL is the only source of progesterone (P(4)) maintaining pregnancy, and they have the capacity to synthesize oestrogens as substantiated by expression of the CYP19 (aromatase) gene observed in this study. Our data demonstrated that lutein and non-lutein cells of the canine CL express in a rather constant manner the progesterone receptor (PR) and the oestrogen receptor, classifying them as targets for an autocrine/paracrine activity of CL-derived steroids. Therefore, a functional role of P(4) within a positive loop feedback system, including StAR and 3β-hydroxysteroid dehydrogenase, has been postulated.

Luteal and placental function in the bitch: spatio-temporal changes in prolactin receptor (PRLr) expression at dioestrus, pregnancy and normal and induced parturition

BackgroundEndocrine mechanisms governing canine reproductive function remain still obscure. Progesterone (P4) of luteal origin is required for maintenance of pregnancy. Corpora lutea (CL) are gonadotrop-independent during the first third of dioestrus; afterwards prolactin (PRL) is the primary luteotropic factor. Interestingly, the increasing PRL levels are accompanied by decreasing P4 concentrations, thus luteal regression/luteolysis occurs in spite of an increased availability of gonadotropic support. PRL acts through its receptor (PRLr), the expression of which has not yet been thoroughly investigated at the molecular and cellular level in the dog.MethodsThe expression of PRLr was assessed in CL of non-pregnant dogs during the course of dioestrus (days 5, 15, 25, 35, 45, 65 post ovulation; p.o.) as well as in CL, the utero/placental compartments (Ut/Pl) and interplacental free polar zones (interplacental sites) from pregnant dogs during the pre-implantation, post-implantation and mid-gestation period of pregnancy and during the normal and antigestagen-induced luteolysis. Expression of PRLr was tested by Real Time PCR, immunohistochemistry and in situ hybridization.ResultsIn non-pregnant CL the PRLr expression was significantly upregulated at day 15 p.o. and decreased significantly afterwards, towards the end of dioestrus. CL of pregnancy showed elevated PRLr expression until mid gestation while prepartal downregulation was observed. Interestingly, placental but not interplacental expression of PRLr was strongly time-related; a significant upregulation was observed towards mid-gestation. Within the CL PRLr was localized to the luteal cells; in the Ut/Pl it was localized to the fetal trophoblast and epithelial cells of glandular chambers. Moreover, in mid-pregnant animals treated with an antigestagen, both the luteal and placental, but not the uterine PRLr were significantly downregulated.ConclusionsThe data presented suggest that the luteal provision of P4 in both pregnant and non-pregnant dogs may be regulated at the PRLr level. Furthermore, a role of PRL not only in maintaining the canine CL function but also in regulating the placental function is strongly suggested. A possible functional interrelationship between luteal P4 and placental and luteal PRLr expression also with respect to the prepartal luteolysis is implied.

Diet-induced impaired glucose tolerance and gestational diabetes in the dog

Glucose metabolism was compared in dogs consuming a chow/meat diet throughout pregnancy (P group, n = 6) and dogs switched to a high-fat/high-fructose (HFF) diet during the 4th-5th gestational week (gestation ≃9 wk; P-HFF group; n = 6). An oral glucose tolerance test (OGTT; 0.9 g/kg) was administered in the 6th-7th gestational week, and a hyperinsulinemic [0-120 min: 1.8 pmol·kg(-1)·min(-1) (low insulin); 120-240 min: 9 pmol·kg(-1)·min(-1) (high insulin)] euglycemic clamp was performed the following week. Nonpregnant (NP) female dogs underwent OGTTs but not clamp studies. All P-HFF dogs exhibited impaired glucose tolerance (IGT) or gestational diabetes (GDM), but only one P dog had IGT. Insulin concentrations in P and P-HFF dogs were significantly lower than in NP dogs 30 and 60 min after the OGTT. Therefore, mean islet size and area were evaluated in P and NP dogs. These values did not differ between groups, and proliferating endocrine cells were rare in pregnancy. During exposure to high insulin, glucose infusion rate and hindlimb glucose uptake were ∼30% greater (P < 0.05) and net hepatic glucose output was more suppressed (-5.5 ± 6.1 vs. 7.8 ± 2.8 mg·100 g liver(-1)·min(-1), P < 0.05) in P than in P-HFF dogs. In conclusion, in the 2nd trimester the canine pancreas does not exhibit islet hypertrophy, hyperplasia, or neogenesis. Combined with the lack of pancreatic adaptation, a HFF diet during late pregnancy produces a canine model of IGT and GDM without hyperinsulinemia but exhibiting liver and muscle insulin resistance.

Histological Study of Canine Mammary Gland During the Oestrous Cycle

The development of the mammary gland is a puzzling phenomenon and the research on this field has been focussed mostly on the carcinogenesis, with a less goal-oriented concern in basic histology. In order to determine the histological features of normal mammary gland in the different oestrous phases we used 39 non-pregnant female dogs of various breeds and ages. The animals were grouped in: pre-pubertal, pro-oestrous, oestrous, early and late dioestrous, early and late anoestrous phases. Major changes of the canine mammary histology throughout the oestrous cycle were identified in this study. A rudimentary gland with few ducts in the base of the nipple was observed in pre-pubertal female individuals and pubertal pro-oestrous female ones. In the oestrus, small inactive lobules associated with ductal branching and inconspicuous regressive changes were observed, while in early dioestrus, a ductal arborization was present. In late dioestrus, a complete lobuloalveolar differentiation and secretory capacity was achieved. The regressive histological features were abundant on early anoestrus, and markedly generalized on late anoestrus. The regressive process was longer in the more caudal gland pairs. This work provides baseline knowledge of canine mammary gland that may be relevant for interspecies comparative purposes and for pathologists dealing with mammary gland tumours.

Canine prostaglandin F2α receptor (FP) and prostaglandin F2α synthase (PGFS): Molecular cloning and expression in the corpus luteum

In the dog luteolysis is not affected by hysterectomy. This observation led to the hypothesis that paracrine/autocrine rather than endocrine mechanisms of PGF2α are responsible for luteal regression in the dioestric bitch. The present experiments tested for the capacity of canine CL to produce and respond to PGF2α by qualitatively and quantitatively determining the expressions of PGFS, the enzyme converting PGH2 into PGF2α, and the PGF2α-receptor (FP) in CL of non-pregnant dogs during dioestrus. Canine PGFS and FP were isolated and cloned; both genes show a high homology (82–94%) when compared to those of other species. Relatively weak FP mRNA expression was detected on day 5 of dioestrus. It had increased by day 25 and remained constant thereafter. In situ hybridization (ISH) localized FP solely to the cytoplasm of the luteal cells, suggesting that these cells are the only luteal targets of PGF2α in this species. Only negative results were obtained for the expression of PGFS in canine CL by routine qualitative RT-PCR. When Real Time (TaqMan) PCR was applied, repetitively more negative than positive results were obtained at all timepoints. Any positive measurements observed at any point were neither repeatable nor related to the stage of dioestrus. This led us to conclude that expression of PGFS is either absent or present at very low level only. These data suggest that luteal regression in non-pregnant bitches is not modulated by PGF2α. However, the FP seems to be constitutionally expressed, explaining the receptivity of canine CL to exogenous PGF2α.

Antioxidant compounds and oxidative stress in female dogs during pregnancy

Pregnancy is a physiological period during which different metabolic pathways are altered, resulting in greater oxygen consumption and modifications of the consumption of energy substrates, with a consequent greater exposure to oxidative stress. The objective of the present study was to determine and describe the serum profile of some antioxidant biomarkers and of oxidative stress markers during pregnancy in healthy dogs. Twenty nonpregnant (NP) and 20 pregnant (P) female dogs were studied. Serum samples were obtained from the animals during the 1st, 3rd, 5th and 7th weeks of pregnancy or during diestrus for the dosage of antioxidant molecules (vitamin E, vitamin A, zinc and magnesium) and oxidative stress markers (TBARS and carbonyl protein). The results revealed a statistically significant difference ( p < 0.05) between the P and NP groups during the 3rd and 5th week for vitamins A and E (NP > P), and between the 1st and 3rd week for magnesium (NP > P). The other parameters did not differ between weeks within the same group or between groups. The present study shows that the levels of antioxidant molecules of pregnant dogs differed from that of nonpregnant dogs. These mechanisms may represent a protection against oxidative stress during this period for this species, a fact that definitely deserves further study. Also, the participation of other protective mechanisms and the interference of the fetal–placental unit with oxidative stress are still unknown.

Hepatic and muscle insulin action during late pregnancy in the dog

We evaluated the effects of physiologic increases in insulin on hepatic and peripheral glucose metabolism in nonpregnant (NP) and pregnant (P; 3rd trimester) conscious dogs (n = 9 each) using tracer and arteriovenous difference techniques during a hyperinsulinemic euglycemic clamp. Insulin was initially (-150 to 0 min) infused intraportally at a basal rate. During 0-120 min (Low Insulin), the rate was increased by 0.2 mU x kg(-1) x min(-1), and from 120 to 240 min (High Insulin) insulin was infused at 1.5 mU x kg(-1) x min(-1). Insulin concentrations were significantly higher in NP than P during all periods. Matched subsets (n = 5 NP and 6 P) were identified. In the subsets, insulin was 7 +/- 1, 9 +/- 1, and 28 +/- 3 microU/ml (basal, Low Insulin, and High Insulin, respectively) in NP, and 5 +/- 1, 7 +/- 1, and 27 +/- 3 microU/ml in P. Net hepatic glucose output was suppressed similarly in both subsets (> or =50% with Low Insulin, 100% with High Insulin), as was endogenous glucose rate of appearance. During High Insulin, NP dogs required more glucose (10.8 +/- 1.5 vs. 6.2 +/- 1.0 mg x kg(-1) x min(-1), P < 0.05), and hindlimb (primarily skeletal muscle) glucose uptake tended to be greater in NP than P (18.6 +/- 2.5 mg/min vs. 13.6 +/- 2.0 mg/min, P = 0.06). The normal canine liver remains insulin sensitive during late pregnancy. Differing insulin concentrations in pregnant and nonpregnant women and excessive insulin infusion rates may explain previous findings of hepatic insulin resistance in healthy pregnant women.

A Screening for the Occurrence of Autoreactive Antibodies in Sera of Pregnant and Non‐pregnant Bitches

Sera of healthy pregnant (group I, n = 11) and non-pregnant (group II, n = 11) bitches were screened for autoantibodies (AAb). In both groups, blood samples were drawn every fifth day between days 5 and 55 after mating. Serum was analysed via indirect immunofluorescence (IIF) with the Canine ANA HEp-2 Screening Kit. In all animals, anticytoplasmic AAb were detected. Utilizing primate-heart substrate slides AAb against contractile proteins of the cytoplasm could be observed. The predominating fluorescence pattern in pregnant animals resembled above all desmin, which was proven via Western blot. The sera were then pre-incubated with tropomyosin, actin, vimentin, vinculin and keratin solutions, and assessed on HEp-2 slides and on human and canine fibroblasts as well. The latter substrate was used to verify whether the detected Ab were in fact AAb. Utilizing tropomyosin, revealed elimination of the cytoplasmic fluorescences on all three substrates. It is therefore assumed, that in sera of healthy dogs, AAb against contractile structure proteins of the cytoplasm are present regularly. The majority of pregnant bitches presented with higher end-point titres (EPT), than to be found in non-pregnant dogs. AAb against desmin played the key role in those patterns. In addition, sera were screened for thyroid specific AAb, namely thyroglobulin, thyroid peroxidase (TPO), T3 and T4, and for AAb against insulin by ELISA or Western blot (TPO). Only in two of the pregnant bitches a weak positive reaction (1:100) for T3-AAb was detected.

The Relaxant Effect of Vasoactive Intestinal Polypeptide in the Isolated Canine Uterine Artery: The Role of Endothelium

The purpose of this study was to examine the effect of vasoactive intestinal polypeptide (VIP) on the uterine artery obtained from non-pregnant dogs. VIP (3 x 10(-9)-3 x 10(-7) M) induced concentration-dependent relaxation in canine uterine arteries with intact endothelium, pre-contracted with 10(-5) M phenylephrine (pEC(50) = 7.52 +/- 0.02, maximal response was 82.19 +/- 2.15%, n = 36). The administration of the cyclooxygenase inhibitor indomethacin (10(-5) M) or 4-aminopyridine (4-AP), a blocker of potassium channels (10(-5) M), did not modify the relaxation induced by VIP. Contrary to this, N(G)-nitro-L-arginine (L-NOARG) (10(-5) M) inhibited relaxation is evoked by VIP. Indomethacin applied with L-NOARG did not provoke further inhibition of VIP-induced relaxation. In the presence of both L-NOARG and L-NOARG + indomethacin, 4-AP led to the further inhibition of VIP-induced relaxation of canine uterine artery. It is concluded that VIP induces endothelium-dependent relaxation of uterine arteries of non-pregnant dogs, which can be entirely explained by the production of nitric oxide (NO) from the endothelial cells. We proposed that when NO synthesis is inhibited, VIP induces further relaxation, independent of the edothelium-derived relaxing factors, probably through activation of K(+) channels.

Regulation of corpus luteum-function in the bitch.

Functional lifespan of the corpus luteum (CL) in non-pregnant dogs exceeds that of pregnant animals and may last for more than 80 days. Prolactin and LH act luteotropic, however, luteolytic mechanisms are poorly understood. Other than in life stock there is no uterine luteolysine and it was postulated that local paracrine/autocrine mechanisms might play a major role. In following this hypothesis the present investigations have clearly demonstrated that up-regulation of prostaglandin synthesis in the CL as indicated by the expression of cyclo-oxygenase II occurs with its formation and not regression, pointing towards a luteotropic rather than luteolytic action. Throughout dioestrus luteal and other cells of the CL express the oestrogen (ERalpha) and progesterone receptor (PR). While ERalpha expression was not cycle-related, PR concentrations were high in the early and late-luteal phase and a regulatory role of both steroids on CL-function is assumed. As in other species also in the dog the immune system seems to participate in the mechanisms regulating CL-function as an increased presence of lymphocytes within the CL could be detected at the beginning [CD4- CD8-, major histocompatibility complex (MHC)II-antigen expressing cells] and during the latter half of dioestrus (CD8- and MHCII-antigen expressing cells). Thus, leucocyte-derived cytokines may be important and the expression of the mRNA for interleukin (IL)8, IL10, IL12, tumour necrosis factor (TNF)alpha and transforming growth factor (TGF) beta1 was observed throughout dioestrus. Electron microscopy confirmed the slow process of luteolysis; first distinct signs of degeneration were seen on day 60, accompanied by some apoptotic events. From these data it is concluded that luteal regression as monitored by the gradual decrease of systemic progesterone concentrations in the dog is not an actively regulated but rather a permissive process. Immune-mediated events may play a key role. Changes in the vascular supply, as indicated by the expression of endoglin, seem to be of lower importance.

Histomorphologic and morphometric evaluation of the uterine horns in nulliparous and multiparous Beagles

To macroscopically, histomorphologically, and morphometrically compare uterine tissues obtained from nulliparous and multiparous dogs. 12 dogs constituting 2 homogenous groups (7 nulliparous Beagles and 5 multiparous Beagles, each of which had at least 7 pregnancies). Serum concentrations of progesterone and estradiol-17beta were determined. Samples of uterine tissues were fixed, embedded in paraffin, and cut into serial cross sections. Morphometric analysis was performed on systematically selected trichrome-stained sections. Mean absolute volume of the uterine wall did not differ between groups. Volume of blood vessels was significantly higher and relative mean value for myometrial connective tissue was significantly lower in the multiparous dogs. Arteries in the myometrium of multiparous dogs had pronounced thickening of the intima (ie, pregnancy sclerosis) and a concomitant thinning of the smooth muscle layer (tunica media). Furthermore, the elastica interna of these arteries appeared to be disintegrating and was highly and irregularly folded. Adventitia of the myometrial veins in multiparous dogs contained numerous layers of elastic fibers; however, only a few layers were observed in the adventitia of corresponding veins in nulliparous dogs. In this study, we documented that in contrast to other species, the uterus of nonpregnant dogs does not increase in size and volume even after at least 7 pregnancies. Furthermore, sclerotic alterations of uterine arteries are proof of at least 1 pregnancy. Results of this study may be useful in the evaluation of uterine diseases.

Plasma von Willebrand factor changes during various reproductive cycle stages in mixed-breed dogs with normal von Willebrand factor and in Doberman Pinschers with type-I von Willebrand's disease

SUMMARY Objective To determine whether plasma von Willebrand factor (vWf) concentration changes during the estrous cycle and pregnancy in Doberman Pinschers with type-I von Willebrand's disease (vWd) and in mixed-breed dogs with normal vWf, and if so, whether alterations in vWf concentration are associated with changes in serum concentrations of reproductive hormones. Animals 5 sexually intact female Doberman Pinschers with type-I vWd and 8 sexually intact female mixed-breed dogs with normal vWf. Procedure Concentrations of plasma vWf and serum progesterone and estradiol-17β were measured during the estrous cycle of nonpregnant dogs and during pregnancy, parturition, and lactation. Serum concentrations of total triiodothyronine, total thyroxin, and free thyroxin were measured during pregnancy, parturition, and lactation. Results Von Willebrand factor concentration did not change during the estrous cycle, but during pregnancy, vWf concentration gradually increased. Peak concentrations were obtained at parturition and were 103 and 92% higher in mixed-breed dogs and dogs with type-I vWd, respectively, than were mean prepregnancy (anestrus) values. At parturition, total triiodothyronine concentration decreased from the prepregnancy value. The increase in vWf concentration during pregnancy was positively associated with changes in concentration of estradiol-17β and was negatively associated with changes in concentration of progesterone. Conclusions The increase in vWf concentration in pregnant bitches may be associated with changes in concentrations of reproductive hormones. However, the increase in vWf concentration during pregnancy may involve other factors because vWf concentration did not change during the estrous cycle of nonpregnant dogs despite increases in concentrations of estradiol-17β and progesterone. (Am J Vet Res 1998;59:111–118)

Long-term observations of uterine contractions in nonpregnant dogs.

Uterine contractile activity in nonpregnant conscious dogs was investigated based on 2- to 6-mo-long continuous recording by means of a chronically implanted force transducer. We found that nonpregnant uterine contractile activity could be classified into six major patterns: sporadic contractions, weak and strong tonic contractions, weak and strong phasic contractions, and phasic contraction bursts. The contractile patterns during proestrus and estrus were the most active, with strong phasic and tonic contractions and phasic contraction bursts. The phasic and tonic contractions were inhibited dose-dependently by a beta 2 adrenergic agonist, ritodrine, and reproduced by an alpha 2 adrenergic agonist, clonidine. In contrast, the cholinergic inhibitors atropine and hexamethonium did not affect the spontaneous occurrence of these contractions, although bethanechol evoked uterine contractions. Oxytocin and prostaglandin F2 alpha-induced contractions were phasic during estrus, whereas they showed tonic increases with phasic contractions during proestrus, diestrus, and anestrus, and these contractions did not resemble the spontaneous contractions. In conclusion, the nonpregnant uterus contracts continuously in harmony with the estrous cycle phases, and its contractile activity is enhanced by alpha adrenergic receptors and inhibited by beta 2 adrenergic receptors.

In vivo investigation of luteal function in dogs: Effects of cabergoline, a dopamine agonist, and prolactin on progesterone secretion during mid-pregnancy and -diestrus

The role of prolactin on luteal function in dogs was investigated in vivo. The function of prolactin in mid-luteal phase was compared in pregnant and nonpregnant dogs. A dopamine agonist, cabergoline, known for its prolactin secretion inhibitory effects, was injected subcutaneously at a dose of 5 μg/kg body weight in five pregnant and five nonpregnant Beagle bitches. Mean plasma prolactin and progesterone were dramatically suppressed for 4 to 5 days after injection in both groups when compared with control pregnant and non-pregnant animals, whereas no effect on luteinizing hormone (LH) secretion was observed. The decline in plasma progesterone occurred after that in prolactin, suggesting plasma progesterone was impaired by inhibition of prolactin secretion. These results confirm the luteotropic importance of prolactin in pregnant bitches, and also demonstrate its importance in luteal phase of the nonpregnant dog. Second, to demonstrate that the effects of cabergoline were mediated by prolactin inhibition and not by a direct action on the corpus luteum, concomitant administration on Day 30 of cabergoline and prolactin (375 μg IV twice daily on Days 30 and 31) or cabergoline and LH (750 μg IV twice daily on Days 30 and 31) was affected in two groups of five pregnant animals each. Results showed that only prolactin was able to reverse the negative effects of cabergoline on circulating progesterone. This confirms the indirect mode of action of the dopamine agonist, cabergoline on corpus luteum function. Third, further investigation on the precise luteotropic role of prolactin was made by IV injection of 375 μg pure canine prolactin twice daily in five pregnant bitches on Days 30 and 31, and in five pregnant bitches on Days 40 and 41. No direct stimulatory effect of prolactin on plasma progesterone secretion occurred. Nor was there a noticeable effect on plasma LH secretion. These results suggest that prolactin is unable to directly stimulate progesterone secretion by the corpus luteum of pregnancy. The results of this study suggest that prolactin is an essential luteotropin in the dog from mid-luteal phase in both pregnant and nonpregnant animals. However, it appears to act by sustaining corpus luteum lifespan and function rather than by direct stimulatory effects on progesterone secretion.

Postimplantation increase in plasma fibrinogen concentration with increase in relaxin concentration in pregnant dogs

Abstract Objective To determine time courses of pregnancy-related changes in plasma fibrinogen, serum relaxin, and serum C-reactive protein-like immunoreactivity (CRP-LI) concentrations in pregnant and nonpregnant dogs. Animals 16 pregnant and 13 nonpregnant Beagles, 6 pregnant Beagles, and 3 pregnant and 3 nonpregnant dogs of other breeds. Procedure Fs'brinogen was measured by nephelometric centrifugal analysis of light scatter in plasma samples of all dogs, and CRP-LI was measured by fluorescence immunoassay in selected sera from 10 pregnant and 10 nonpregnant dogs. Relaxin was measured in selected sera from 7 pregnant and 7 nonpregnant dogs. Results During pregnancy, fibrinogen concentration increased between days 21 and 30 after the luteinizing hormone surge, and was &gt; 280 mg/dl between days 29 and 50 in 84 of 86 samples, with peak values 539 ± 29 mg/dl higher (P &lt; 0.01) than those in nonpregnant dogs (188 ± 8 mg/dl), higher values from days 21 to 50 (P &lt; 0.01) than those in nonpregnant dogs, and values similar to those in nonpregnant dogs after day 50. Relaxin concentration was increased from days 26 to 30 and 0 to 4 days after fibrinogen concentration increased in pregnant dogs, and was not detectable in nonpregnant dogs. The CRP-LI concentration was higher in pregnant dogs at days 26 to 50, but values were inconsistent within and among dogs, and near the limit of sensitivity of the assay. Conclusions Concentration of the acute-phase reactant protein fibrinogen increases after day 20 following implantation in dogs, at or just before the pregnancy-specific increase in relaxin concentation from days 26 to 30, and persists until day 50. Clinical Relevance Fibrinogen assay may be useful for pregnancy diagnosis in dogs. (Am J Vet Res 1996;57:1382–1385)

Changes in the baroreflex during pregnancy in conscious dogs: heart rate and hormonal responses.

This study was performed to test the hypothesis that reflex increases in heart rate, PRA, and plasma concentrations of vasopressin, angiotensin-II, ACTH, and cortisol are reduced during pregnancy. The hypothesis was tested by measuring, in pregnant and nonpregnant conscious dogs, changes in arterial and atrial pressures, heart rate, and plasma hormone concentrations during 30-min infusions of three doses of nitroprusside (1, 2, and 4 micrograms/kg.min). Between-group differences were determined by comparing the relationships between arterial or atrial pressure and plasma hormone concentrations. Hypotension-induced increases in heart rate and plasma levels of vasopressin, ACTH, and cortisol were blunted when the dogs were pregnant. In contrast, reflex increases in PRA and angiotensin-II were increased. These results indicate that the activity of the baroreceptor reflex is altered during pregnancy in dogs.

Ritodrine inhibition of hypoxic pulmonary vasoconstriction

The effect of ritodrine hydrochloride on hypoxic pulmonary vasoconstriction (HPV), the normal control mechanism for shunting blood flow away from nonventilated areas of the lung, was studied in nonpregnant dogs equipped with central monitors and electromagnetic flow probes. The systemic infusion of ritodrine at a dose of 4 μg/kg/min resulted in a 66.4% ± 4.6% decrease in the HPV response, whether administered before or after the induction of isolated lobar hypoxia. These findings have significant implications for the patient who develops pulmonary edema during ritodrine therapy, in which inability to bypass nonventilated areas of the lung would serve to aggravate further the ventilation/perfusion inequalities that already exist.

A simplified technique to produce toxemia in the pregnant dog

In 39 pregnant and six nonpregnant dogs the abdominal aorta was exposed extraperitoneally through a left paralumbar incision, and a vascular occluder and a flow transducer were placed around it. The tubing of the occluder and the wiring of the flow transducer were slipped under the skin and advanced to the back of the neck of the animal. Thus, the aortic blood flow could be progressively reduced and continuously monitored. After 4 to 20 days of blood flow reduction of 35% to 75%, the picture of a moderately severe toxemia appeared in 10 dogs and that of a mild toxemia was seen in the 11 others. Nine animals were eliminated because of premature labor and three were eliminated for surgical complications. The control group (six pregnant animals with a sham operation and six nonpregnant animals with a severe aortic constriction) presented no abnormalities.

Pregnancy blunts pulmonary vascular reactivity in dogs.

Pregnancy decreases systemic vascular reactivity but comparatively little is known about the effects of pregnancy on the pulmonary circulation. Pulmonary vascular resistance (PVR) during acute hypoxia was lower (P < 0.01) in eight intact anesthetized pregnant dogs compared to the same animals postpartum. Mean pulmonary arterial pressure (Ppa) and PVR during infusion of prostaglandin (PG) F2 alpha were also reduced during pregnancy. Nonpregnant female dogs (n = 5) treated with estrogen (0.001 mg x kg-1 x da-1) for 2 wk had decreased Ppa (P < 0.01) during acute hypoxia compared to control measurements, but PVR was unchanged during hypoxia and PGF2 alpha infusion. Treatment with progesterone in four dogs had no effect on pulmonary vascular reactivity to hypoxia or PGF2 alpha. Inhibition of circulating PG with meclofenamate in four dogs during pregnancy did not appear to restore pulmonary vascular reactivity. Blunted pulmonary vascular reactivity is suggested by the limited data available for women, but is not seen in pregnant cows. We conclude that pregnancy decreases pulmonary as well as systemic vascular reactivity in the dog, but the mechanism is unclear.