A Bolus Dose of PTH 1‐84 Elicited Sustained Elevations in Intramedullary Pressure in Rat Femora

Abstract

BACKGROUNDPrevious studies demonstrated that chronic increases and decreases in bone intramedullary pressure (IMP) augments and reduces bone mass, respectively. Parathyroid hormone (PTH) plays a central role in the regulation of bone remodeling and augments bone mass. We previously reported augmented vasodilation of the femoral principal nutrient artery (PNA) to cumulative doses of PTH 1‐84, PTH 1‐34 and PTHrP 1‐34. In addition, bone perfusion is augmented following a bolus dose of PTH. Since PTH increases vasodilation and blood flow, we sought to assess its effects on bone IMP. The purpose of the study was to sequentially examine IMP in rat femora following PTH administration.METHODSMale Wistar rats (3–5 months) were randomly divided into the following groups: Control (CON, n = 7), PTH120 (n = 7), PTH150 (n = 7), and PTH330 (n = 7). Rats were anesthetized (2% isoflurane to O2 balance) and right femoral shafts were catheterized. At this time, the PTH groups received PTH 1‐84 (100 μg/kg, s.c.) and CON received PBS (100 μl, s.c.). The rats were sacrificed 120, 150 and 330 minutes following surgery. Just prior to sacrifice, the catheter was connected to a pressure transducer and in vivo IMP (mmHg) was recorded (PowerLab, AD Instruments) in the conscious rodents. The last 10 minutes of data were averaged and reported. Alpha level was set a priori at p<0.05 and One‐way ANOVA and Student Newman‐Keuls post hoc were performed to determine group differences.RESULTSBody mass did not differ among groups: CON, 478 ± 8 g; PTH120 474 ± 9 g; PTH150, 458 ± 6 g; PTH330, 488 ± 4 g. IMP was augmented (p<0.05) at PTH120 (33 ± 3 mmHg), PTH150 (35 ± 6 mmHg), PTH330 (41 ± 4 mmHg) vs. CON (20 ± 3 mmHg). IMP did not differ among the PTH groups.CONCLUSIONPTH increased bone IMP and sustained this response for up to 5 1/2 hours (i.e., 330 min) following administration. This increase in pressure corresponds with reports of enhanced vasodilation and bone perfusion following bolus administration of PTH. Given the bone altering effects of chronic IMP modulation, enhanced IMP with PTH administration may represent another mechanism by which it induces bone anabolism.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.