Intermittent Parathyroid Hormone Administration and Aortic Stiffness in Young and Old Fischer‐344 Rats
Authors: Prisby Rhonda , Guers John , Kim Jahyun 
Published: November 2023

Background

Arterial stiffness is a predictor for cardiovascular disease and mortality and is strongly correlated with advancing aging. Arterial stiffness is caused by alterations in the structural properties of blood vessels. Intermittent parathyroid hormone (PTH) administration positively impacts bone mass and health. While the primary purpose of intermittent PTH administration is to increase bone mass in elderly individuals, PTH elicits vasodilation in blood vessels. Therefore, secondary and unintended benefits of intermittent PTH administration in patients with low bone mass may include modifications in the functional and structural properties of the vascular system. The aim of this study was to investigate the effects of 15 days of intermittent PTH (1–34) administration on structural and mechanical properties of rat aortae.

Methods

Young (4–6 months) and old (22–24 months) male Fisher‐344 rats were divided accordingly: 1) young control (CON, n=4–8), 2) young PTH (n=5–11), 3) old CON (n=4–6) and old PTH (n=5–8). Rats were given PTH 1–34 (43 μg/kg/day) or PBS (100 μL/day) 5 days a week for 2 weeks. The structural properties assessed were 1) percent elastin, 2) percent collagen, 3) wall thickness and 4) luminal diameter. The mechanical properties assessed were 1) stress‐strain and 2) stiffness‐strain. Overall stiffness was determined by the slope of the stiffness‐stress curve.

Results

Percent elastin was lower (p<0.05) in old CON (28±7%) and old PTH (30±3%) vs. young CON (56±4%) and young PTH (46±2%) and PTH tended (p=0.07) to attenuate percent elastin young rats. Percent collagen was higher (p<0.05) in old CON (33±2%) vs. young CON (19±3%), young PTH (19±1%) and old PTH (25±1%), whereby PTH attenuated (p<0.05) percent collagen in old rats. Wall thickness (p<0.05) was greater in old CON (109±6 μm) vs. young CON (84±4 μm) and young PTH (90±2 μm). Wall thickness in old PTH (99±5 μm) did not differ from young PTH and old CON but was thicker (p<0.05) than young CON. Luminal diameters were larger (p<0.05) in old CON (1445±32 μm) and old PTH (1379±31 μm) vs. young CON (1273±21 μm) and young PTH (1256±17 μm). Luminal diameter tended (p=0.07) to be reduced in old PTH vs. old CON. The stress‐strain relationship did not differ among groups. Aortae were stiffer (i.e., stiffness‐strain relationship; p<0.05) in old CON vs. young CON and young PTH. Stiffness did not differ among old PTH, young CON and young PTH. Overall stiffness was augmented (p<0.05) in old CON (3.1±0.1 AU) and old PTH (2.8±0.1 AU) vs. young CON (2.3±0.2 AU) and young PTH (2.4±0.1 AU). Overall stiffness tended (p=0.07) to be lower in old PTH vs. old CON.

Conclusion

Intermittent PTH administration tended to reduce overall stiffness and lowered collagen content in aortae from old rats. Thus, while used as a treatment for osteoporosis in elderly individuals, PTH may have unrecognized benefits on the mechanical properties of systemic blood vessels.

Support or Funding Information

National Institute of Arthritis and Musculoskeletal and Skin Diseases Award #: 7R15AR062882‐02 (RP)