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The sleep apnea-hypopnea syndrome (SAHS) involves periods of intermittent hypoxia, experimentally reproduced by exposing animal models to oscillatory PO 2 patterns. In both situations, chronic intermittent hypoxia (CIH) exposure produces carotid body (CB) hyperactivation generating an increased input to the brainstem which originates sympathetic hyperactivity, followed by hypertension that is abolished by CB denervation. CB has dopamine (DA) receptors in chemoreceptor cells acting as DA-2 autoreceptors. The aim was to check if blocking DA-2 receptors could decrease the CB hypersensitivity produced by CIH, minimizing CIH-related effects. Domperidone (DOM), a selective peripheral DA-2 receptor antagonist that does not cross the blood-brain barrier, was used to examine its effect on CIH (30 days) exposed rats. Arterial pressure, CB secretory activity and whole-body plethysmography were measured. DOM, acute or chronically administered during the last 15 days of CIH, reversed the hypertension produced by CIH, an analogous effect to that obtained with CB denervation. DOM marginally decreased blood pressure in control animals and did not affect hypoxic ventilatory response in control or CIH animals. No adverse effects were observed. DOM, used as gastrokinetic and antiemetic drug, could be a therapeutic opportunity for hypertension in SAHS patients' resistant to standard treatments.

Objective: To determine the efficacy and tolerability of a long-acting dihydropyridine in the clinical settings of general practice., Material and Methods: 110 essential hypertensives were included (age 62.3 +/- 10.8 years, 51 men and 53 women, 38/ obese -IMC >30 kg/m2, ten diabetics). 104 patients ended the followup. Patients were treated with lercanidipine 10 mg once daily in the morning. Follow-up lasted 6 months. When blood pressure was not controlled (BP < 140/90 mmHg) in any visit, a second drug was added, excluding calcium channel blockers. Antiadrenergic drugs were recommended. If patients were not controlled ittwo consecutive visits they were excluded from follow-up., Results: Significant reductions in both systolic (baseline 157.4 +/- 11.7 vs 131.1 +/- 6.8 mmHg, p < 0,001) and diastolic BP (baseline 94.7 +/- 5.8 vs 80.0 +/- 5.5 mmHg, p < 0,001) were attained at six months. Mean SBP decrease was 26.7 mmHg and mean DBP reduction was 15.6 mmHg. At the study end, 84.3/ of the patients achieved a BP < 140/90 mmHg. Thirty patients needed a second drug to become controlled (26 at the study end). The overall incidence of adverse effects was 4,4/ (n=6) and just three patients withdrew the treatment due to untoward effects. Plasmatic cholesterol lowered from 225.3 +/- 41.0 to 216.7 +/- 25.3 mg/dl (p = 0,03) and urate decreased from 5.6 +/- 1.6 to 5.1 +/- 1.4 mgldl, p = 0,03)., Conclusions: Lercanidipine is a calcium channel blockers of high efficacy and low incidence of adverse effects in the clinical settings of general practice. It seems to have a positive metabolic effects on plasmatic levels of cholesterol and urate.

Key points: Episodes of intermittent hypoxia, as produced in obstructive sleep apnoea, cause a carotid‐driven sympathetic hyperactivity and an oxidative status leading to cardiovascular and metabolic pathologies, which are less pronounced in patients >60–65 years old.In young rats (3–4 months) chronic intermittent hypoxia augments carotid body hypoxic responses, plasma catecholamine, renal catecholamine content and turnover, produces an oxidative status, and causes hypertension.In aged rats (22–24 months) chronic intermittent hypoxia does not alter carotid body responses, catecholamine‐related parameters or redox status, and does not cause hypertension.It is concluded that age affords protection to harmful effects produced by chronic intermittent hypoxia.Possible mechanisms involved in age protection and the significance of our findings in the diagnosis and therapeutic approaches to obstructive sleep apneoa in the elderly are considered. Obstructive sleep apnoea (OSA) affects an estimated 3–7% of the adult population, the frequency doubling at ages >60–65 years. As it evolves, OSA becomes frequently associated with cardiovascular, metabolic and neuropsychiatric pathologies defining OSA syndrome (OSAS). Exposing experimental animals to chronic intermittent hypoxia (CIH) can be used as a model of the recurrent hypoxic and O2 desaturation patterns observed in OSA patients. CIH is an important OSA event triggering associated pathologies; CIH induces carotid body (CB)‐driven exaggerated sympathetic tone and overproduction of reactive oxygen species, related to the pathogenic mechanisms of associated pathologies observed in OSAS. Aiming to discover why OSAS is clinically less conspicuous in aged patients, the present study compares CIH effects in young (3–4 months) and aged (22–24 months) rats. To define potential distinctive patterns of these pathogenic mechanisms, mean arterial blood pressure as the final CIH outcome was measured. In young rats, CIH augmented CB sensory responses to hypoxia, decreased hypoxic ventilation and augmented sympathetic activity (plasma catecholamine levels and renal artery content and synthesis rate). An increased brainstem integration of CB sensory input as a trigger of sympathetic activity is suggested. CIH also caused an oxidative status decreasing aconitase/fumarase ratio and superoxide dismutase activity. In aged animals, CIH minimally affected CB responses, ventilation and sympathetic‐related parameters leaving redox status unaltered. In young animals, CIH caused hypertension and in aged animals, whose baseline blood pressure was augmented, CIH did not augment it further. Plausible mechanisms of the differences and potential significance of these findings for the diagnosis and therapy of OSAS are discussed. Key points: Episodes of intermittent hypoxia, as produced in obstructive sleep apnoea, cause a carotid‐driven sympathetic hyperactivity and an oxidative status leading to cardiovascular and metabolic pathologies, which are less pronounced in patients >60–65 years old.In young rats (3–4 months) chronic intermittent hypoxia augments carotid body hypoxic responses, plasma catecholamine, renal catecholamine content and turnover, produces an oxidative status, and causes hypertension.In aged rats (22–24 months) chronic intermittent hypoxia does not alter carotid body responses, catecholamine‐related parameters or redox status, and does not cause hypertension.It is concluded that age affords protection to harmful effects produced by chronic intermittent hypoxia.Possible mechanisms involved in age protection and the significance of our findings in the diagnosis and therapeutic approaches to obstructive sleep apneoa in the elderly are considered. [ABSTRACT FROM AUTHOR]

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. J. Cell. Physiol. 226: 1961-1969, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]