Mammary blood flow and metabolic activity are linked by a feedback mechanism involving nitric oxide synthesis

Abstract

To test which, if any, of the major milk precursors can elicit a rapid change in the rate of mammary blood flow (MBF) and to define the time course and magnitude of such changes, 4 lactating cows were infused with glucose, amino acids, or triacylglycerol into the external iliac artery feeding one udder half while iliac plasma flow (IPF) was monitored continuously by dye dilution. Adenosine and saline were infused as positive and negative controls, respectively, and insulin was infused to characterize the response to a centrally produced anabolic hormone. To test the roles of cyclooxygenase, NO synthase and ATP-sensitive K (K ATP ) channels in nutrient-mediated changes in blood flow, their respective inhibitors-indomethacin, N ω -nitro-Larginine methyl ester hydrochloride (L-NAME), and glibenclamide-were infused simultaneously with glucose. Each day, 1 infusate was given twice to each cow, over a 20-min period each time, separated by a 20-min washout period. In addition, each treatment protocol was administered on 2 separate days. A 73% increase in IPF during adenosine infusion showed that the mammary vasodilatory response was quadratic in time, with most changes occurring in the first 5 min. Glucose infusion decreased IPF by 9% in a quadratic manner, most rapidly in the first 5 min, indicating that a feedback mechanism of local blood flow control, likely through adenosine release, was operative in the mammary vasculature. Amino acid infusion increased IPF 9% in a linear manner, suggesting that mammary ATP utilization was stimulated more than ATP production. This could reflect a stimulation of protein synthesis. Triacylglycerol only tended to decrease IPF and insulin did not affect IPF. A lack of IPF response to glibenclamide indicates that K ATP channels are not involved in MBF regulation. Indomethacin and L-NAME both depressed IPF. In the presence of indomethacin, glucose infusion caused a quadratic 9% increase in IPF. Indomethacin is an inhibitor of mitochondrial function, so the glucoseinduced increase in IPF was interpreted as feedback on mammary adenosine release from an anabolic response to glucose. Because NO synthase was not inhibited during indomethacin infusion, the feedback system is postulated to act through endothelial NO synthase. In the presence of L-NAME, glucose infusion had no effect on IPF, indicating that endothelial cyclooxygenase is not involved in glucose-induced changes in MBF.

Dietary arginine supplementation in multiparous sows during lactation improves the weight gain of suckling piglets

“…Both NO and polyamines play critical roles in mammary angiogenesis, milk production and consequent growth of the litter. Enhanced synthesis of NO from Arg may mediate increased mammary blood flow, thereby increasing nutrient delivery for milk production (Meininger and Wu 2002;Kim and Wu 2009;Cieslar et al 2014). Increased plasma NO concentration at d 21 of lactation from Arg supplementation at d 21 of lactation was consistent with this but it was impractical to measure blood flow in the present study.…”

AMPK-mTOR pathway is involved in glucose-modulated amino acid sensing and utilization in the mammary glands of lactating goats

“…This decrease was consistent with the decreased supply of AA (particularly EAA) and mammary uptake in these animals. Thus, it appears that when a high dosage of glucose was given, AA availability to the MG was inhibited, and may have mainly resulted from a trend of decreased MPF in these animals observed in both our previous study [5] and another study [34]. In addition, our previous study showed that high dosage of glucose resulted in acute glycolysis in mammary epithelial cells (MEC), accumulated reactive oxygen species and decreased the antioxidant capacity of MEC [5].…”

The market for amino acids: understanding supply and demand of substrate for more efficient milk protein synthesis

“…In the short term, mammary blood flow is positively regulated by nitric oxide through a feedback signal from adenosine, which indicates a decrease in cellular energy, and is negatively regulated by glucose [61]. On the other hand, longer-term glucose or starch infusion increased mammary blood flow [34,62,63].…”