Background Vitamin D deficiency is linked to cardiovascular and respiratory instability, particularly during hypoxic stress, such as in obstructive sleep apnea (OSA). However, the mechanisms connecting vitamin D status to hemodynamic and cardiorespiratory responses in hypoxia remain unclear. Objective This study aimed to assess the impact of vitamin D deficiency on hemodynamic (mean arterial pressure and heart rate) and cardiorespiratory (respiratory rate and peripheral oxygen saturation) stability in an OSA experimental model, along with the effects of dose-dependent vitamin D supplementation. Methods Fifty-six adult male Sprague Dawley rats were divided into seven groups: control, vitamin D-deficient, vitamin D-deficient with severe intermittent hypoxia (IH) and supplementation subgroups exposed to varying levels of IH. Vitamin D deficiency was induced through a diet lacking vitamin D for three weeks, followed by oral supplementation at two doses (25 µg/kg/day and 37.5 µg/kg/day) for two weeks. Intermittent hypoxia was simulated for 14 days, and serum 25-hydroxyvitamin D (25OHD) levels were measured using Elisa. Hemodynamic and cardiorespiratory parameters were recorded, and heart, aorta tissue were analyzed. Results Vitamin D-deficient groups exhibited significantly lower serum 25OHD levels and showed increased mean arterial pressure, heart and respiratory rates, and reduced oxygen saturation under hypoxia. High-dose supplementation improved 25OHD levels and improved physiological measures, particularly in moderate hypoxia subgroups (p = 0.001). Conclusion Vitamin D deficiency combined with intermittent hypoxia increased mean arterial pressure, heart rate, and respiratory rate, reduced oxygen saturation, and worsened cardiovascular histology. Vitamin D supplementation improved these changes, especially at higher dose, and protected cardiovascular structures. Graphical Abstract Vitamin D deficiency combined with intermittent hypoxia induces hemodynamic and respiratory instability and causes cardiovascular tissue alterations. Vitamin D supplementation improves physiological parameters, with greater effects at higher dose, and preserves heart and aortic structure in an obstructive sleep apnea rat model.

Background: Endothelial dysfunction driven by intermittent hypoxia (IH)-induced oxidative stress, nitric oxide depletion, and adhesion molecule upregulation underlies obstructive sleep apnea (OSA)-related cardiovascular complications. Vitamin D deficiency, which frequently coexists with OSA, may further amplify this endothelial injury through impaired endothelial nitric oxide synthase (eNOS) regulation and heightened renin-angiotensin-aldosterone system (RAAS) activity; however, the dose-dependent therapeutic potential of vitamin D3 on combined endothelial and renal outcomes in an IH model remains uncharacterized. Methods: Fifty-six adult male Sprague-Dawley rats were allocated to seven groups: control, vitamin D-deficient (VDD), VDD with severe IH (SIH-VDD), and four supplementation subgroups receiving high-dose (37.5 μg/kg/day) or low-dose (25 μg/kg/day) cholecalciferol under severe or moderate IH for 14 days. Serum E-selectin, ICAM-1, ET-1, NO, and PCSK9 were quantified by ELISA. Renal histopathology was assessed on H&E sections by a blinded pathologist. Data were analyzed by one-way MANOVA, univariate ANOVA, and LSD post hoc tests (p < 0.05). Results: The SIH-VDD group showed the most severe endothelial activation: peak E-selectin (4.92 ± 0.90 ng/mL), ICAM-1 (201.50 ± 21.55 ng/mL), ET-1 (5.31 ± 0.81 pg/mL), and PCSK9 (213.50 ± 14.71 ng/mL), with the lowest NO (14.88 ± 2.16 μmol/L; all p < 0.001 vs. control). High-dose supplementation produced substantial recovery across all markers; PCSK9 normalized to near-control (162.50 ng/mL) under severe IH. Low-dose supplementation yielded incomplete normalization. Renal histopathology revealed mild interstitial lymphocytic infiltration in IH-exposed groups, with proximal tubular vacuolisation exclusively in the SIH-VDD group and entirely absent in all supplemented groups. Glomerular architecture remained preserved throughout. Conclusion: Vitamin D deficiency combined with IH upregulates endothelial dysfunction markers and induces renal tubular injury in an experimental OSA model. High-dose vitamin D ₃ attenuates these changes dose- and severity-dependently, supporting its role as a pharmacological adjunct for OSA-associated endothelial and renal complications.