Chronic Intermittent Hypoxia Alters Endothelial and Smooth Muscle Cell-Mediated Relaxation in Rat Femoral Arteries

Introduction: Chronic intermittent hypoxia (CIH) is associated with elevated sympathetic nerve activity (SNA) and hypertension (HTN). However, specific effects of CIH on vascular function and the relation to the development of hypertension remain unclear. The objective of this study is to characterize the interplay between endothelial and smooth muscle function on rat femoral vessels following 7 days of mild chronic intermittent hypoxia. We hypothesize that CIH alters vascular reactivity through modification of endothelial and smooth muscle function, leading to an increased risk of developing HTN. Methods: Sprague-Dawley male rats (225-400g) were divided into 2 groups by treatment: Normoxic (CON) and CIH. CON rats were housed in normal conditions with food and water ad libitum. CIH rats were kept in chambers with cycling oxygen concentrations that dropped from 21% to 10%. Each cycle lasted 6 minutes, with 10 cycles conducted per hour, over an 8-hour period each day (8 AM–4 PM), for 7 consecutive days. After one week of this CIH protocol, the rats were anesthetized with 2-3% isoflurane, euthanized, and femoral artery rings were prepared for wire myography experiments. Isometric tension recordings were used to quantify concentration-dependent responses to adrenergic agonists phenylephrine (PE) (10 - 8 M to 10 - 4 M) (n= 8 CON, 8 CIH), dobutamine (DOB) (10 - 8 M to 10 - 4 M) (n= 12 CON, 5 CIH), and acetylcholine (ACh) (10 - 10 M to 10 - 4 M) (n= 16 CON, 9 CIH). Endothelium-dependent mechanisms were evaluated by comparing ACh-mediated relaxation between groups. Results: CIH exposure did not influence PE mediated contractions. However, we observed a significant interaction between DOB dose and CIH treatment indicating that CIH may have altered vascular sensitivity to beta-adrenergic relaxation across DOB doses (p=0.004). Endothelium-dependent relaxation to ACh was increased following CIH (p=0.001). While there was no difference in the maximum ACh relaxation, CIH increased the sensitivity to ACh (a rightshift in the EC50 from 20 nM to 1 nM). Conclusion: Overall, increased ACh-mediated relaxation may compensate for impaired beta-adrenergic relaxation and may also offset elevated SNA that would promote alpha-adrenergic contraction despite unchanged alpha receptor function by PE. The changes in ACh-mediated relaxation in CIH vessels may reflect endothelial adaptations to help alleviate increased vasoconstriction associated with CIH-associated HTN. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.