Increase In Mammary Blood Flow Research Articles

Responses in splanchnic and mammary amino acid metabolism to short-term graded removal of methionine in lactating goats.

Four multi-catheterized lactating goats were used in a 4×4 Latin square experiment to investigate the responses of amino acid metabolism in portal-drained viscera (PDV), liver, and mammary glands to short-term varying supplies of methionine (Met). During the last 45h in each experimental period, goats were fasted for 12h and then abomasally infused with an amino acid (AA) mixture plus glucose for 33h. Treatments consisted of graded removal of Met from an infused AA mixture to achieve Met content in the infusate of 100% (complete), 60%, 30%, or 0% that in casein. Graded Met removal decreased the production of milk, milk protein, lactose, and fat linearly whilst also decreasing arterial Met concentration linearly (P<0.05). Meanwhile, net PDV uptake and liver removal of Met decreased linearly (P<0.05) due to decreased Met affinity of PDV and liver (P<0.05). Net mammary uptake of Met (P>0.1) was maintained as Met supply declined. This was achieved through increased mammary affinity (P<0.05) and increased mammary blood flow (P<0.05) totally offsetting the negative effect of decreased circulating Met concentration. Graded removal of Met from the infusate linearly decreased mammary uptake-to-milk output ratios of Met (P<0.05) and tended to decrease essential amino acid (EAA) linearly (0.05<P<0.1). Treatments also linearly decreased circulating concentration of prolactin and linearly increased insulin concentration (P<0.05). In conclusion, results of the present study indicated there were several mechanisms used to mitigate a Met deficiency, including reduced catabolism of Met in PDV, liver, and peripheral tissue (including mammary glands) and a linear increase in mammary blood flow. The observed decreases in milk protein production as Met supply decreased appear to be a result of regulatory events which may have been driven by decreased circulating prolactin, rather than as a result of decreased mammary Met uptake.

Effects of Long Term Exogenous Bovine Somatotropin on Nutrients Uptake by the Mammary Gland of Crossbred Holstein Cattle in the Tropics

Ten, first lactation, 87.5%HF dairy cattle were used to investigate effects of long-term administration of recombinant bovine somatotropin (rbST) on nutrient uptake by the mammary gland at different stages of lactation. Measurements of arterial plasma concentrations and arterial-venous differences of metabolites across the mammary gland were performed in combination with measurment of mammary blood flow to estimate the mammary uptake. Animals in experimental groups were injected subcutaneously every 14 days from day 60 of lactation with a prolonged-release formulation of 500 mg of rbST (POSILAC, Monsanto, USA) or with sterile sesame oil without rbST in the control group. During early lactation, the milk yield of rbST-treated animals was higher than that of the control animals (p<0.05). The peak milk yield in both groups of animals declined from the early period of lactation with progression to mid- and late-lactation. No significant changes were observed in the concentration of milk lactose, while the concentrations of milk protein significantly increased as lactation advanced to mid- and late-lactation in both groups. Milk fat concentrations were significantly higher in rbST-treated animals than in control animals, particularly in early lactation (p<0.05). Mammary blood flow (MBF) markedly increased during rbST administration and was maintained at a high level throughout lactation. The mean arterial plasma concentrations for glucose and acetate of rbST-treated animals were unchanged. The net mammary glucose uptake of rbST-treated animals increased approximately 20% during early lactation, while it significantly decreased (p<0.05), including the arteriovenous differences (A-V differences) and extraction ratio across the mammary gland, as lactation advanced to mid- and late- lactation. A-V differences, mammary extraction and mammary uptake for acetate increased during rbST administration and were significantly higher (p<0.05) than in the control animals in early and mid-lactation. Mean arterial plasma concentrations for β- hydroxybutyrate and free glycerol were unchanged throughout the experimental periods in both groups. A-V differences and extraction ratio of β-hydroxybutyrate across the mammary gland did not alter during rbST administration. Mean arterial plasma concentrations for free fatty acids (C16 to C18), but not for triacylglycerol, increased in rbST-treated animals and were significantly higher than in control animals during early lactation (p<0.01). These findings suggest that an increase in MBF during rbST administration would not be a major determinant in the mediation of nutrient delivery and uptake by the mammary gland for increased milk production. Local changes in biosynthetic capacity within the mammary gland would be a factor in the utilization of substrates resulting in the rate of decline in

Effects of long-term exogenous bovine somatotropin on water metabolism and milk yield in crossbred Holstein cattle

The present study was conducted to evaluate the effects of long-term administration of recombinant bovine somatotropin (rbST) on the regulation of body fluids, mammary blood flow (MBF) and other variables relevant to milk synthesis, in crossbred dairy cattle (0·875 of Holstein–Friesian (HF) genes and 0·125 Red Shindi (RS) genes. Ten first lactation, non-pregnant, animals were chosen and divided into the control and experimental groups of five animals each. Four consecutive measurements were carried out in each group beginning on days 45 (pre-treatment), 105, 165 and 225 of lactation. Animals that had completed 60 days of lactation were injected subcutaneously every 14 days with 500 mg of rbST (POSILAC, Monsanto, USA) in the experimental group, while animals in the control group were injected subcutaneously every 14 days with 800 mg of sterile sesame oil, without rbST, as a control. All animals were fed with rice straw treated with 50 g urea/l as the source of roughage in combination with a similar concentrate throughout the experiments. During the treatment periods, the daily dry matter intake (DMI) was numerically greater for rbST-treated animals than for control animals, while the relative values of DMI per kg body weight and water intake showed no differences.Animals in both groups gained weight throughout the experiment with no significant differences between the groups. Animals receiving rbST for 45 days increased their peak milk yield from 13·4 kg/day per animal during pre-treatment to 15·9 kg/day per animal (18·7% increase) on day 105 of measurement and this peak yield was higher (19·5%) than those of control animals in the same period. Milk yields on days 225 in late lactation of both groups significantly decreased (P<0·05) in comparison with the early and mid-lactating periods. Over the course of the experiment, milk yield of the rbST-treated animals was significantly higher than those of the control animals (P<0·01). The administration of rbST significantly increased MBF (P<0·05) and mammary plasma flow (MPF) (P<0·01). The ratio of MBF to milk yield slightly increased as lactation advanced in both controls and rbST-treated animals. The administration of rbST significantly increased the absolute values of both plasma volume (P<0·01) and blood volume (P<0·05) when compared with the control animals. The control animals showed no significant changes in values of extracellular water (ECW) throughout the course of treatment periods. The rbST-treated animals increased in both the absolute values and the relative (proportion of body weight) values of ECW throughout the experiment (P<0·05). The estimated values of intracellular water (ICW) in both groups showed no significant changes during the course of treatments. There were no significant changes in the water turnover rate (WTO) and the biological half-life of tritiated water in different periods of lactation in both groups. The absolute values of total body water space (TOH) and total body water (TBW) were significantly greater in rbST-treated than control animals (P<0·05). The relative values of both TOH and TBW as a proportion of body weight of control animals decreased, while no alteration was apparent in rbST-treated animals during the course of treatments. These differences were statistically significant (P<0·05). The absolute values of empty body water (EBW) of the control animals showed no significant changes, while animals treated with rbST tended to increase in absolute values of EBW throughout the course of treatments. The effects of these differences were statistically significant (P<0·05). There were no significant changes in relative values of EBW during the course of treatments in both controls and rbST-treated animals. These data demonstrated that the rbST exerts its galactopoietic action in part through increases in TBW, EBW and ECW in association with an increase in MBF, which partitions the distribution of nutrients to the mammary gland for milk synthesis. During this long-term administration of rbST, the stimulant effect for milk yield was less in late lactation despite a higher MBF. The decline in milk yield during rbST treatment without fall in MBF in late lactation must be attributed to a local change within the mammary gland.

Relationship of Early Lactation and Bovine Somatotropin to Water Metabolism and Mammary Circulation of Crossbred Holstein Cattle

The study was carried out to evaluate the effect of exogenous bovine somatotropin on water metabolism in relation to mammary function in early lactation of crossbred Holstein cattle. Ten, 87.5% crossbred Holstein cattle were divided into two groups of 5 animals each. At day 60 of lactation, the control group was given placebo while animals in the experimental group were given recombinant bovine somatotropin (rbST) by subcutaneous injection with 500 mg of rbST (14-days prolonged-release rbST). In rbST- treated animals, milk yield increased 19.8%, which coincided with a significant increase in water intake (p<0.01), while DM daily intake was not different when compared to the control animals. Water turnover rate as absolute values significantly increased (p<0.05), while the biological half-life of water did not change in rbST-treated animals. Total body water (TBW) and total body water space (TOH) as absolute values significantly increased (p<0.01) in rbST-treated animals, while it was decreased in the control animals. Absolute values of empty body water (EBW) markedly increased (p<0.05), which was associated with an increase in the extracellular fluid (ECF) volume. Absolute values of plasma volume and blood volume were also significantly increased (p<0.05) in rbST-treated animals. The increase in mammary blood flow in rbST-treated animals was proportionally higher than an increase in milk production. The plasma IGF-1 concentration was significantly increased (p<0.01) in rbST-treated animals when compared with those of control animals during the treatment period. Milk fat concentration increased during rbST treatment, while the concentrations of both protein and lactose in milk were not affected. The present results indicate that rbST exerts its effect on an increase in both TBW and EBW. An increased ECF compartment in rbST-treated animals might partly result from the decrease in fat mass during early lactation. The action of rbST on mammary blood flow might not be mediated solely by the action of IGF-1 for increase in blood flow to mammary gland. An elevation of body fluid during rbST treatment in early lactation may be partly a result of an increase in mammary blood flow in distribution of milk precursors to the gland. (Asian-Aust. J. Anim. Sci. 2005. Vol 18, No. 11 : 1600-1608)

Mammary Blood Flow Does Not Limit Milk Yield in Lactating Goats

There is a close relationship between mammary blood flow (MBF) and milk production, but whether MBF is limiting milk yield has not been determined. Five lactating goats received close arterial (external pudic) infusion of PBS or the nitric oxide donor diethylamine NONOate (0.5 mg/h; NONate) for 6h, according to a crossover design. Goats were hand milked (with oxytocin) every 2h starting 2h before and ending 6h after the end of the infusion. In one goat, a transit time flow probe was implanted around the infused and noninfused artery, whilst in another goat a flow probe was implanted around the infused artery only. Infusion of PBS did not affect MBF or milk production. As with previous results (Lacasse et al., 1996), NONate induced a rapid increase (up to 250% of preinfusion level) in MBF in the infused gland only. Mammary blood flow was still above the preinfusion level at the end of the infusion period. Despite this increase in MBF, NONate did not affect milk production. Milk yield ratio (infused/noninfused gland) averaged 1.20, 1.12, and 1.17 for the preinfusion, infusion and post infusion periods, respectively. Similarly, protein, fat and lactose yields were not affected by PBS or NONate infusion. These results provide no support to the contention that increasing MBF can enhance milk production.

Effects of Exogenous Bovine Somatotropin on Mammary Function of Late Lactating Crossbred Holstein Cows

The objective of the present study was to determine the effect of exogenous bovine somatotropin on the mammary function in late lactating crossbred Holstein cows. Twelve 87.5% late lactating Holstein cows, approximately 30 weeks postpartum, were divided into two groups of 6 animals each. Animals in the control group were given sodium bicarbonate buffer by subcutaneous injection, while animals in the treated group were given recombinant bovine somatotropin (bST) by subcutaneous injection with 500 mg of bST (14 day prolonged-release bST). After bST injection, milk yield significantly increased from the control level on day 8 to day 20 (p<0.05) with a concomitant increase in mammary blood flow (p<0.01). An increase in mammary blood flow in response to bST treatment was greater than an increase in milk production. An increased plasma concentration of IGF-I coincided with an increase in mammary blood flow in animals treated with bST. There were no significant changes in the concentration of arterial plasma glucose concentration, the arteriovenous concentration difference (A-V difference) and mammary extraction ratio while the mammary glucose uptake increased when compared to the control group. The concentration of arterial plasma triglyceride decreased throughout the experimental period in animals give bST. The plasma concentration of acetate, and the mammary uptake for acetate significantly increased (p<0.05) after bST treatment. The action of bST did not affect the plasma concentration, A-V difference and extraction ratio across the mammary gland for β-hydroxybutyrate. The concentrations of milk fat and lactose tended to increase during bST treatment. Milk protein concentration initially increased in the first few days and decreased after bST injection when compared to the pretreated period. The present results indicated that bST could affect the mammary function in late lactating cows by increase in milk yield involving changes in both extra-mammary and intra-mammary mechanisms. The exogenous bST exerted its galactopoietic action through an increase in circulating IGF-I of the late lactating Crossbred Holstein cattle. (Asian-Aust. J. Anim. Sci. 2003. Vol 16, No. 1 : 88-95)

Studies on cutaneous blood flow in the mammary gland of lactating rats.

The mechanisms that regulate mammary blood flow during lactation are not fully understood. In the present study laser Doppler flowmetry (LDF) was used to measure blood flow in the cutaneous microvessels of the mammary gland of lactating rats. The effects of suckling on blood flow were examined, as were those of local injection of oxytocin (0.5-5 mU) and the vasoactive peptides calcitonin gene-related peptide (CGRP; 0.1-10 pmol), vasoactive intestinal polypeptide (VIP; 0.4-20 pmol) and neuropeptide Y (NPY; 1-40 pmol). Blood flow responses to suckling varied depending on how much time had lapsed since the previous suckling. In rats with milk in the gland, suckling caused an initial increase in blood flow. In connection with milk let-down, the blood flow decreased, but was followed by a second increase. In recently suckled rats with no milk in the gland the increase in blood flow corresponded to the number of pups suckling. Oxytocin injections also had varying effects on mammary blood flow depending on how recently suckling had taken place. In non-suckled rats with milk in the gland, oxytocin injections caused a rise in blood flow that was interrupted by a fall during milk ejection. In recently suckled rats, all doses of oxytocin caused an increase in blood flow of similar magnitude. However, the effect of the higher doses had a longer duration. CGRP and VIP injections caused a dose-dependent increase in mammary blood flow regardless of when suckling last occurred. NPY injections caused a dose-dependent decrease in blood flow.

EGTA-induced disruption of epithelial cell tight junctions in the lactating caprine mammary gland.

The suitability of the Ca2+ chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) to induce disruption of mammary tight junctions (TJ) and its effect on milk secretion were investigated in six goats. EGTA was administered via the teat of one gland as an isosmotic (300 mosmol/l) K-EGTA solution (68 mM EGTA), whereas the control gland received an isosmotic sucrose solution. Lactose, Na, K, and Cl in milk, blood lactose, and the presence of Evans blue (EB) in mammary lymph were used as indicators of TJ disruption. EGTA caused transient (approximately 60 h) changes (P < 0.05) in the concentration of lactose, K, Na, and Cl in milk, consistent with loss of TJ integrity. This was confirmed by a rapid (< 1 h) increase (P < 0.05) in blood lactose levels. Moreover, EB appeared in lymph < 1 h after EGTA+EB treatment. Milk secretion declined unilaterally by 15% (P < 0.05) after EGTA and did not return to baseline until approximately 60 h after EGTA. EGTA caused a unilateral, temporary (first 7 h) increase in mammary blood flow. This study shows that a rapid temporary disruption of mammary TJ can be successfully induced in vivo and that such disruption compromises milk secretion.

Increased mammary blood flow in the lactating goat induced by parathyroid hormone‐related protein

Human synthetic parathyroid hormone-related protein (PTHrP) increased mammary blood flow (MBF) following close-arterial infusion via the external pudic artery in goats during mid-lactation. MBF increased 74 +/- 8% within 30 min of the start of continuous infusion of PTHrP compared with 10 +/- 3% in controls. MBF decreased by 90 min, however, and was not different from control values for the remainder of the infusion. The increase in plasma concentrations of calcium and decrease in phosphate during PTHrP suggests that this was not due to altered activity of PTHrP, but may relate to downregulation of response or production of counter-regulatory vasoconstrictive agents within the gland. This problem was alleviated when PTHrP was infused in a pulsatile fashion. An average 14-40% increase in MBF was achieved over 6 h, but this did not alter the rate of milk secretion, suggesting that mammary hyperaemia is not sufficient by itself to increase milk yield in the normally lactating goat. MBF increased in a dose-dependent fashion, although the lowest dose used to give a detectable response was approximately 40-fold higher than the concentration normally present in the mammary venous circulation. Thus, endogenous PTHrP may not be an important regulator of MBF during lactation in the goat.

Parathyroid hormone-related peptide may increase mammary blood flow.

Amino-terminal fragments of PTHrP were previously shown to increase regional blood flow in laboratory animals. Since PTHrP is produced in the lactating mammary gland and associated nutrient vessels, we examined the effects of peptide fragments of PTHrP on the hemodynamics of the mammary gland of dried sheep. The left arterial mammary blood flow measured using ultrasonic flow probes in four dried Lacaune ewes was 233 +/- 11 ml/minute. It was significantly increased when synthetic human PTHrP-(1-34) or (1-86) fragments were injected into the mammary artery. The effect was dose dependent for PTHrP-(1-34), varying between 0.0075 and 0.3 nmol/kg body weight. PTHrP-(140-173) fragment lacked any vasorelaxant activity. Synthetic human endothelin (ET1) decreased arterial blood flow in a dose-dependent manner. This decrease was inhibited by PTHrP-(1-34), and this inhibition was PTHrP dose related. When ET1 (10 pmol/kg body weight) was injected together with PTHrP-(1-86) (100 pmol/kg body weight), only a significant increase in mammary blood flow was observed. Thus, PTHrP produced by the lactating mammary gland may be involved in the regulation of mammary blood flow.

Studies on mammary blood flow during experimental E. coli endotoxin mastitis.

The effect of intramammary (i.mam.) infusion ofEscherichia coli lipopolysaccharides (LPS) upon mammary blood flow (MBF) was studied in lactating goats using the electromagnetic flow technique. After i.mam. LPS administration mastitis, accompanied by a significant increase in MBF, occurred. This phenomenon showed two conspicuous peaks which occurred 11/2h and 8–10h after LPS administration. Other symptoms were: fever, increased heart rate, swelling and pain of the gland, increased chloride (MCl−) and total cell count (TC) in milk. Since there was a marked coincidence between the increment stage of fever and the break-down of MBF peak I, studies were performed to evaluate the possible role of fever in this typical biphasis MBF pattern.

The relationship of changes in mammary blood flow and plasma progesterone at the time of parturition in the ewe

Previous studies indicate that there is a fall in maternal plasma progesterone and a marked increase in mammary blood flow (MBF) at the time of parturition in ewes. In this experiment the role of progesterone as a cause of this increase in MBF was investigated. Progesterone was infused (9.9 mcg. per minute) into a branch of the mammary artery in five sheep during the induction of premature labor by fetal dexamethasone infusion (1 mg. per 24 hours) to prevent the normal fall in concentration of local mammary artery progesterone. Five ewes used as controls received a mammary artery infusion of cholesterol (9.9 mcg. per minute). In the cholesterol-infused group MBF increased significantly from baseline values after 13 ± 4 hours (mean ± standard error) to a peak flow of 235 ± 9 ml. per minute. In the group receiving the progesterone the increase in MBF was delayed to 35 ± 7 hours, reaching only 161 ± 22 ml. per minute. These results were significantly different from control group results (p < 0.01). This study suggests that the fall in maternal plasma progesterone which occurs at the time of parturition may play a role in the increase in MBF that occurs prior to the onset of labor, delivery, and lactogenesis.

Mammary blood flow during experimental Escherichia coli endotoxin induced mastitis in goats and cows

The effect of intramammary infusion of Escherichia coli endotoxin upon mammary blood flow was studied in lactating goats and cows. Blood flow was recorded by means of an electromagnetic flow probe chronically implanted around one mammary artery. Endotoxin mastatis was always accompanied by a significant increase in mammary blood flow, characterized by 2 conspicuous peaks. The flow returned to control values by the thirteenth hour after infusion. Other symptoms of acute mastitis were: fever, increased heart rate, swelling, heat and pain of the gland, increased chloride and total cell count in milk.

Mammary blood flow and endocrine changes during parturition in the ewe.

The temporal relationship between changes in mammary blood flow (MBF) and changes in the concentration of plasma prolactin, progesterone, estradiol-17beta, and cortisol, was examined in chronic sheep preparations undergoing spontaneous labor (Group I) or labor induced by an infusion of dexamethasone (1 mg/24 h) to the fetus (Group II). In Group I, an increase in prolactin (45 to 489 ng/ml), a decrease in progesterone (15 to 4 ng/ml), and an increase in MBF (97 to 365 ml/min) occurred at about the same time, whereas increases in estradiol-17beta (80 to 211 pg/ml) and cortisol (9 to 39 ng/ml) followed the change in MBF. A similar pattern of changes in MBF and hormonal concentrations occurred over a shorter period when premature labor was induced in the animals in Group II. These findings suggest that changes in plasma prolactin and progesterone concentrations play an important role in the regulation of MBF at the time of parturition.

Relationship of mammary blood flow to parturition in the ewe.

Mammary blood flow was measured in conscious, unanesthetized ewes with electromagnetic flow probes prior to spontaneous labor (four animals) or during the induction of premature labor (four animals) by administration of dexamethasone, 1 mg/24 h, to the fetus. In all animals an increase in mammary blood flow was noted prior to delivery. Dexamethasone administered to one mother in the same dose did not induce labor or produce an increase in mammary blood flow. These results suggest that the fetal adrenal gland influences maternal mammary blood flow prior to delivery.