Organ and Tissue Perfusion Subsequent to Short‐Term Intermittent PTH 1–34 Administration in Mature and Middle‐Aged Mice

Abstract

IntroductionIntermittent parathyroid hormone (PTH) administration is used to treat osteoporosis; however, the secondary benefits of PTH treatment are under explored. PTH elicits vasodilation in the systemic vasculature, implying improved delivery of blood flow to various tissues. Intermittent administration of PTH 1–84 and PTH 1–34 for 15 days augmented and tended to augment vasodilation of the femoral principal nutrient artery in young (p<0.05; Prisby et al., 2013) and old (p=0.07; Lee et al., ASBMR 2014) rats, respectively. Further, intermittent PTH 1–84 administration enhanced skeletal tibial perfusion in mice (Roche et al., 2014). Given the influence of PTH on the vascular system, we sought to determine if short‐term intermittent PTH administration alters organ and tissue perfusion.MethodsMature (6–8mon) and middle‐aged (10–12mon) male and female C57BL/6 mice were equally divided into three groups (i.e., CON, 5dPTH and 10dPTH). Mice were given either PTH 1–34 (43 μg/kg/d) or PBS (50 μl) for 5 and 10 consecutive days. Under anesthesia, fluorescent microspheres were injected into the left ventricle. At sacrifice, the myocardium, left and right gastrocnemii, solei, and kidneys were dissected. Tissue fluorescent density (TFD, AU/g) was determined as tissue fluorescence ÷ tissue mass. Data were excluded if organs and tissues contained <200 fluorescent beads (Prinzen et al., 2000, Cardinal et al., 2007).ResultsBody and tissue masses were similar among groups. There were age‐related declines (p<0.05) in perfusion measured by TFD to the right gastrocnemius (6–8mon: 20273 ± 473 AU/g vs. 10–12mon: 17181 ± 520 AU/g), and left gastrocnemius (6–8mon: 18993 ± 473 AU/g vs. 10–12mon: 16699 ± 676 AU/g). There was a tendency (p<0.10) for lower perfusion to the right kidney (6–8mon: 19409 ± 276 AU/g vs. 10–12mon: 18498 ± 385 AU/g) and left kidney (6–8mon: 19073 ± 567 AU/g vs. 10–12mon: 17503 ± 480 AU/g) in middle‐aged mice. TFD in the myocardium and right and left solei were not altered (p>0.05) by age. In contrast, TFD in other organs and soft tissues was not altered (p>0.05) by either 5 or 10 days of PTH.ConclusionOrgan and tissue perfusion is reduced in middle‐aged vs. mature mice. However, organ and muscle perfusion did not change following short‐term intermittent PTH 1–34 administration. Additional studies are required to determine the influence of intermittent PTH administration on organ and tissue perfusion or blood flow in conscious animals.Support or Funding InformationSupported by the University of Delaware Research Foundation Strategic Initiative Grant and NIH NIAMS (7R15AR062882‐02).