The impact of aging and sex on diaphragm vasomotor function
Authors: Horn Andrew , Kunkel Olivia , Schulze Kiana , Weber Ramona , Poole David , Behnke Bradley 
Published: May 2023

INTRODUCTION: Advancing age is associated with a decline in endothelium-dependent vasodilation in skeletal muscle resistance vessels which constrains skeletal muscle blood flow capacity. This age-related endothelial dysfunction is due primarily to reduced nitric oxide (NO) bioavailability and alterations in endothelial nitric oxide synthase (eNOS) activation. Whereas it is well recognized that advancing age impairs peripheral skeletal muscle vasomotor control, whether similar impairments occur in the respiratory muscle vasculature (i.e. diaphragm) and in a sex-specific manner, is unknown. Therefore, we tested the hypothesis that old age will impair endothelial-dependent dilation, independent of sex, in diaphragm resistance vessels. METHODS: 5 month old Sprague-Dawley (n=6) and 20 month old Fisher 344 (n=9) rats were divided into three groups: young control (YC; n=6), old female (OF; n=6) and old male (n=3). Under pentobarbital sodium anesthesia, the diaphragm was removed and first-order arterioles (1A) from the medial costal diaphragm were isolated, cannulated, and pressurized at 90 cmH2O and allowed to equilibrate for 60 min to develop spontaneous tone. Thereafter, endothelium-dependent and -independent vasorelaxation responses to cumulative doses of acetylcholine (ACh; 10-9 to 10-4M) in the absence and presence of L-NAME (10-5), and sodium nitroprusside (SNP; 10-9 to 10-4M) were determined. RESULTS: There were no differences in spontaneous tone development (%) or maximal diameter (μm) between YC (31 ± 3%; 170 ± 7 μm), OF (28 ± 1%; 178 ± 9μm) and OM rats (31 ± 1%; 185 ± 16μm) (all P>0.05). Maximal ACh-mediated relaxation (%) was significantly reduced in OM (64 ± 3%) versus OF (74 ± 2%;P<0.05) and both OM and OF ACh-mediated relaxation was decreased compared to YC (85 ± 4%; P<0.05). Age-related and sex differences in endothelial-dependent relaxation were abolished in the presence of L-NAME (P<0.05). There were no differences in maximal endothelium-independent relaxation (%) in response to SNP with age or sex (YC: 85 ± 4%; OF: 79 ± 5%; OM: 81 ± 4%; P>0.05). CONCLUSION: These findings demonstrate that similar to locomotory skeletal muscle, advancing age impairs endothelial function in diaphragm resistance arterioles with no effect on vascular smooth muscle function. In addition, there was a greater reduction in endothelial-dependent vasorelaxation in aged male rats compared to aged female rats. The data herein suggest that aging induces endothelial dysfunction in the diaphragm microvasculature via reduced NO bioavailability. Further, these data demonstrate potential sex differences in NO bioavailability and/or eNOS function in the diaphragm vasculature of aged rats. This work was supported by the National Institute of Aging (1 R15 AG 078060). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.