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.