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: Surfactant Protein D (SP-D) is a critical immunomodulatory collectin maintaining alveolar homeostasis. Obstructive sleep apnea (OSA)-related intermittent hypoxia (IH) disrupts pulmonary surfactant integrity; however, severity-dependent SP-D dynamics remain incompletely characterized. This study explores SP-D as a potential indicator of IH-induced alveolar stress and evaluates whether Galectin-3 (Gal-3) inhibition modulates surfactant homeostasis. Methods: Forty adult male Sprague-Dawley rats (8 per group) were randomized to Control (normoxia), Moderate IH (MIH; 15–30 events/hour), Severe IH (SIH; 30–60 events/hour), MIH + Gal-3 inhibitor (Modified Citrus Pectin, 800 mg/kg/day), or SIH + Gal-3 inhibitor. IH exposure lasted 8 h/day for 10 days. Outcomes included circulating SP-D, Surfactant Protein B (SP-B), inflammatory markers, physiological parameters, and histopathological lung injury scores assessed via American Thoracic Society guidelines. Results: SP-D levels showed numerical reductions with increasing IH severity (Control: 1969.07 pg/mL [IQR: 262.15]; SIH: 1404.30 pg/mL [IQR: 351.88]), representing a 28.6% decrease. However, between-group variability resulted in non-significant omnibus testing (Kruskal–Wallis p = 0.187). Gal-3 inhibition elevated SP-D levels, particularly in severe IH (2133.95 pg/mL [IQR: 1240.70]), though high inter-individual variability was observed (CV = 58.1%). SP-B showed significant suppression under moderate IH (p = 0.019) with restoration by treatment. Exploratory correlation analysis revealed moderate positive associations between SP-D and heart rate (r = 0.587) and respiratory rate (r = 0.419) in severe IH, though these did not reach statistical significance (p = 0.126 and p = 0.301, respectively). Histologically, severe IH induced diffuse alveolar damage (total lung score: 19.67 ± 0.82). Gal-3 inhibition produced context-dependent effects: protective in severe IH but paradoxically exacerbating inflammation under moderate IH (29.20 ± 4.64 vs. 20.00 ± 4.34; p < 0.05). Gal-3 inhibition significantly attenuated cardiac injury (injury score: 0.00 ± 0.00 vs. 7.17 ± 0.75 in severe IH; p < 0.001, η² = 0.859). Conclusions: SP-D demonstrates severity-associated alterations consistent with alveolar epithelial stress during IH, though high variability limits definitive biomarker validation in this sample. Gal-3 inhibition modulates surfactant homeostasis and attenuates cardiopulmonary injury in a context-dependent manner. These findings support further investigation into SP-D as a component of multimodal severity stratification in OSA and highlight Gal-3 inhibition as a context-dependent anti-inflammatory strategy, pending validation in larger cohorts with tissue-level confirmation.