Effects of Intermittent Hypoxia on Blood Gases Plasma Catecholamine and Blood Pressure

Producción CientíficaObstructive sleep apnoea syndrome (OSAS) is a disorder characterized by repetitive episodes of complete (apnoea) or partial (hypopnoea) obstruction of airflow during sleep. The severity of OSAS is defined by the apnoea hypopnoea index (AHI) or number of obstructive episodes. An AHI greater than 30 is considered severe, but it can reach values higher than 100 in some patients. Associated to the OSA there is high incidence of cardiovascular and neuro-psychiatric pathologies including systemic hypertension, stroke, cardiac arrhythmias and atherosclerosis, diurnal somnolence, anxiety and depression. In the present study we have used a model of intermittent hypoxia (IH) of moderately high intensity (30 episodes/h) to evaluate arterial blood gases and plasma catecholamines as main effectors in determining arterial blood pressure. Male rats were exposed to IH with a regime of 80s, 20% O2 // 40s, 10%O2, 8 h/day, 8 or 15 days. Lowering the breathing atmosphere to 10% O2 reduced arterial blood PO2 to 56.9mmHg (nadir HbO2 86, 3%). Plasma epinephrine (E) and norepinephrine (NE) levels at the end of 8 and 15 days of IH showed a tendency to increase, being significant the increase of norepinephrine (NE) levels in the group exposed to intermittent hypoxia during 15 days. We conclude that IH causes an increase in sympathetic activity and a concomitant increase in NE levels which in turn would generate an increase in vascular tone and arterial blood pressure.Este trabajo fue financiado por BFU2007-61848 (MEC, Spain), CIBER CB06/06/0050 (FISS-ICiii) and by JCyL grant: GR242.3

Carotid body function and ventilatory responses in intermittent hypoxia. evidence for anomalous brainstem integration of arterial chemoreceptor input

Obstructive sleep apnea is a frequent medical condition consisting in repetitive sleep-related episodes of upper airways obstruction and concurrent events of arterial blood hypoxia. There is a frequent association of cardiovascular diseases and other pathologies to this condition conforming the obstructive sleep apnea syndrome (OSAS). Laboratory models of OSAS consist in animals exposed to repetitive episodes of intermittent hypoxia (IH) which also develop cardiovascular pathologies, mostly hypertension. The overall OSAS pathophysiology appears to be linked to the repetitive hypoxia, which would cause a sensitization of carotid body (CB) chemoreflex and chemoreflex-driven hyperreactivity of the sympathetic nervous system. However, this proposal is uncertain because hyperventilation, reflecting the CB sensitization, and increased plasma CA levels, reflecting sympathetic hyperreactivity, are not constant findings in patients with OSAS and IH animals. Aiming to solve these uncertainties we have studied the entire CB chemoreflex arch in a rat model of IH, including activity of chemoreceptor cells and CB generated afferent activity to brainstem. The efferent activity was measured as ventilation in normoxia, hypoxia, and hypercapnia. Norepinephrine turnover in renal artery sympathetic endings was also assessed. Findings indicate a sensitization of the CB function to hypoxia evidenced by exaggerated chemoreceptor cell and CB afferent activity. Yet, IH rats exhibited marked hypoventilation in all studied conditions and increased turnover of norepinephrine in sympathetic endings. We conclude that IH produces a bias in the integration of the input arising from the CB with a diminished drive of ventilation and an exaggerated activation of brainstem sympathetic neurons. © 2010 Wiley-Liss, Inc..Peer Reviewe

Effects of cigarette smoke and hypoxia on pulmonary circulation in the guinea pig

Producción CientíficaCigarette smoke (CS) and chronic hypoxia (CH) can produce pulmonary hypertension. Similarities and differences between both exposures and their interaction have not been explored. The aim of the present study was to investigate the effects of CS and CH, as single factors or in combination, on the pulmonary circulation in the guinea pig. 51 guinea pigs were exposed to CS for 12 weeks and 32 were sham-exposed. 50% of the animals in each group were additionally exposed to CH for the final 2 weeks.We measured pulmonary artery pressure (Ppa), and the weight ratio between the right ventricle (RV) and left ventricle plus the septum. Pulmonary artery contractility in response to noradrenaline (NA), endothelium-dependent vasodilatation and distensibility were evaluated in organ bath chambers. The number of small intrapulmonary vessels showing immunoreactivity to smooth muscle (SM) a-actin and double elastic laminas was assessed microscopically. CS and CH induced similar increases of Ppa and RV hypertrophy (p,0.05 for both), effects that were further enhanced when both factors were combined. CH increased the contractility to NA (p,0.01) and reduced the distensibility (p,0.05) of pulmonary arteries. Animals exposed to CS showed an increased number of small vessels with positive immunoreactivity to SM a-actin (p,0.01) and those exposed to CH a greater proportion of vessels with double elastic laminas (p,0.05). We conclude that CH amplifies the detrimental effects of CS on the pulmonary circulation by altering the mechanical properties of pulmonary arteries and enhancing the remodelling of pulmonary arterioles.The study was funded by grants from FIS (04/1424), the European Union (2005-018725, Pulmotension), BFU2007-61848 (DGICYT), CIBER CB06/06/0050 (ISCIII) and JCyL-GR242