Intermittent parathyroid hormone administration attenuates endothelial dysfunction in old rats
We have demonstrated that intermittent parathyroid hormone administration can rescue age-related vascular dysfunction by improving endothelial-dependent dilation in the aorta of older rodents. This demonstrates a novel potential benefit of parathyroid hormone administration in aging. Aging is an independent risk factor for cardiovascular disease and is characterized by a decline in endothelial function. Parathyroid hormone (PTH) administration has been shown to increase endothelial nitric oxide synthase (eNOS) expression. The purpose of this investigation was to determine the effect of intermittent PTH administration on aortic endothelial function in old rodents. We hypothesized that intermittent PTH administration would improve endothelial function in older rodents. Old (24-mo-old) and young (4-mo-old) Fischer-344 rats were given 10 injections of PTH 1–34 (43 μg·kg −1 ·day −1 ) or phosphate-buffered saline (100 μl/day) over 15 days. Endothelium-dependent relaxation of aortic rings in response to acetylcholine (10 −9 to 10 −5 M) was significantly impaired in old control (OC) compared with young control (YC) as indicated by a reduced area under the curve (AUC, 100 ± 6.28 vs. 54.08 ± 8.3%; P < 0.05) and impaired maximal relaxation (E max , 70.1 ± 4.48 vs. 92.9 ± 4.38%; P < 0.05). E max was improved in old animals treated with PTH (OPTH) (OC, 70.1 ± 4.48 vs. OPTH, 85 ± 7.48%; P < 0.05) as well as AUC (OC, 54.08 ± 8.3 vs. OPTH, 82.5 ± 5.7%; P < 0.05) while logEC 50 was not different. Endothelial-independent relaxation in response to sodium nitroprusside was not different among groups. Aortic eNOS protein expression was significantly decreased in OC compared with YC ( P < 0.05). PTH treatment restored eNOS expression in OPTH animals ( P < 0.05). These data suggest that PTH may play a role in attenuating age-related impairments in aortic endothelial function. NEW & NOTEWORTHY We have demonstrated that intermittent parathyroid hormone administration can rescue age-related vascular dysfunction by improving endothelial-dependent dilation in the aorta of older rodents. This demonstrates a novel potential benefit of parathyroid hormone administration in aging.
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