Effects of aging on vasoconstrictor responses of diaphragm arterioles

Abstract

Introduction: In health, the diaphragm is the most important inspiratory muscle and the only skeletal muscle that is continuously recruited throughout life. Because of the diaphragm’s importance to generating the exercise hyperpnea and wealth of evidence that diaphragm fatigue and exhaustion can impair exercise tolerance, we were interested in whether the exercise intolerance that attends older populations might be associated with altered diaphragm vasomotor control. While it is known that aging compromises peripheral skeletal muscle vasomotor control, it is not known if similar impairments are present in the respiratory muscle vasculature, namely the diaphragm. Therefore, we tested the hypothesis that advanced age decreases diaphragm arteriole contractile responses to alpha-adrenergic agonists. Methods: 4–5 month old Fischer rats and 22–24 month old Fischer rats were divided by age into two groups: young (Y) and old (O). In Y and O, diaphragm first order (1A) arterioles (~200μm diameter, ~2μm in length) were isolated, cannulated, and pressurized to develop spontaneous tone. Following this, contractile responses to cumulative doses of norepinephrine (NE) and phenylephrine (PE) (10−9 to 10−4M) were determined. Results and Conclusion: The physical characteristics of the two groups differed as O were heavier than Y. However, with respect to the diaphragm 1A arterioles, there were no differences in spontaneous tone development (%) or maximal diameter (μm) between Y (38 ± 4%; 132 ± 19μm) and O (37 ± 4%; 157 ± 14 μm; both P >0.05). In diaphragm 1A arterioles, the maximal vasoconstrictor response to NE was also not different between O and Y animals (O: 37 ± 8% vs. Y: 45 ± 1%; p > 0.05). However, the maximal vasoconstrictor response to PE was greater in Y compared to O (O: 29 ± 3% vs. Y: 39 ± 5%; p ≤ 0.05). These data support that aging may reduce a1 adrenergic receptor mediated vascular control, altering the vasoconstrictive responsiveness of diaphragm resistance vessels. We are increasing our group sizes to test the robustness of this conclusion. This work was supported by the Sustained Momentum for Investigators with Laboratories Established (SMILE) Grants awarded to T.I.M and D.C.P. by Kansas State University College of Veterinary Medicine and the National Institute on Aging 1R15AG078060 awarded to B.J.B and D.C.P. A.G.H and K.M.S. were financially supported by Ruth L. Kirschstein National Research Service Awards 1F31HL167618-01 and 1F31HL170643-01, respectively. This is the full abstract presented at the American Physiology Summit 2024 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.