Maladaptive Pulmonary Vascular Responses to Chronic Sustained and Chronic Intermittent Hypoxia in Rat

Chronic sustained hypoxia (CSH), as found in individuals living at a high altitude or in patients suffering respiratory disorders, initiates physiological adaptations such as carotid body stimulation to maintain oxygen levels, but has deleterious effects such as pulmonary hypertension (PH). Obstructive sleep apnea (OSA), a respiratory disorder of increasing prevalence, is characterized by a situation of chronic intermittent hypoxia (CIH). OSA is associated with the development of systemic hypertension and cardiovascular pathologies, due to carotid body and sympathetic overactivation. There is growing evidence that CIH can also compromise the pulmonary circulation, causing pulmonary hypertension in OSA patients and animal models. The aim of this work was to compare hemodynamics, vascular contractility, and L-arginine-NO metabolism in two models of PH in rats, associated with CSH and CIH exposure. We demonstrate that whereas CSH and CIH cause several common effects such as an increased hematocrit, weight loss, and an increase in pulmonary artery pressure (PAP), compared to CIH, CSH seems to have more of an effect on the pulmonary circulation, whereas the effects of CIH are apparently more targeted on the systemic circulation. The results suggest that the endothelial dysfunction evident in pulmonary arteries with both hypoxia protocols are not due to an increase in methylated arginines in these arteries, although an increase in plasma SDMA could contribute to the apparent loss of basal NO-dependent vasodilation and, therefore, the increase in PAP that results from CIH.

Successful Response to Cyclophosphamide, Vincristine, and Dacarbazine Chemotherapy in a Patient with Metastatic Carotid Body Paraganglioma

Carotid body paraganglioma is a rare neuroendocrine tumor presenting with low-grade histological and clinical features. However, the tumor has the potential to produce distant metastasis, and due to its rarity, little information is available regarding chemotherapy for such metastatic lesions. Here, we report a case of carotid body paraganglioma with development of pulmonary and bone metastases 10 years after radical surgery for the primary lesion in the neck. The lesions showed a good response to cyclophosphamide, vincristine, and dacarbazine chemotherapy. A beneficial therapeutic outcome by chemotherapy is extremely rare in patients with metastatic carotid body paraganglioma.

Testosterone Supplementation Induces Age-Dependent Augmentation of the Hypoxic Ventilatory Response in Male Rats With Contributions From the Carotid Bodies

Excessive carotid body responsiveness to O2 and/or CO2/H+ stimuli contributes to respiratory instability and apneas during sleep. In hypogonadal men, testosterone supplementation may increase the risk of sleep-disordered breathing; however, the site of action is unknown. The present study tested the hypothesis that testosterone supplementation potentiates carotid body responsiveness to hypoxia in adult male rats. Because testosterone levels decline with age, we also determined whether these effects were age-dependent. In situ hybridization determined that androgen receptor mRNA was present in the carotid bodies and caudal nucleus of the solitary tract of adult (69 days old) and aging (193–206 days old) male rats. In urethane-anesthetized rats injected with testosterone propionate (2 mg/kg; i.p.), peak breathing frequency measured during hypoxia (FiO2 = 0.12) was 11% greater vs. the vehicle treatment group. Interestingly, response intensity following testosterone treatment was positively correlated with animal age. Exposing ex vivo carotid body preparations from young and aging rats to testosterone (5 nM, free testosterone) 90–120 min prior to testing showed that the carotid sinus nerve firing rate during hypoxia (5% CO2 + 95% N2; 15 min) was augmented in both age groups as compared to vehicle (<0.001% DMSO). Ventilatory measurements performed using whole body plethysmography revealed that testosterone supplementation (2 mg/kg; i.p.) 2 h prior reduced apnea frequency during sleep. We conclude that in healthy rats, age-dependent potentiation of the carotid body’s response to hypoxia by acute testosterone supplementation does not favor the occurrence of apneas but rather appears to stabilize breathing during sleep.

Carotid Body Inflammation: Role in Hypoxia and in the Anti-inflammatory Reflex

Emergent evidence indicates that the carotid body (CB) chemoreceptors may sense systemic inflammatory molecules, and is an afferent-arm of the anti-inflammatory reflex. Moreover, a pro-inflammatory milieu within the CB is involved in the enhanced CB chemosensory responsiveness to oxygen following sustained and intermittent hypoxia. In this review, we focus on the physio-pathological participation of CBs in inflammatory diseases, such as sepsis and intermittent hypoxia.