Renal and cardiac effects of renal sympathetic denervation and carotid baroreceptor stimulation.

Cumulative evidence nowadays supports the dominant role of sympathetic nervous system (SNS) activation in patients with hypertension, congestive heart failure, and renal dysfunction. During the last years innovative interventional treatments [renal sympathetic denervation (RSD) and baroreflex activation therapy (BAT)] have emerged and accompanied by sustained reductions of blood pressure (BP) levels. Moreover, these promising therapies are favorable not only on BP regulation but also on the SNS overdrive-related organ damage. The present review focuses on the association of SNS activation with renal and cardiac diseases and presents the cardiorenal effects of RSD and BAT in experimental and clinical settings.

The activation of endothelin-1 pathway during methionine-induced homocysteinemia mediates endothelial dysfunction in hypertensive individuals.

OBJECTIVES: Endothelin-1 (ET-1) is a key regulator of arterial blood pressure in humans, and homocysteinemia is associated with increased oxidative stress. It is still unclear whether homocysteine-induced oxidative stress is implicated in the regulation of ET-1 expression. We examined the impact of acute homocysteinemia on endothelial function in hypertensive patients and healthy individuals, and the potential role of ET-1. METHODS: In this double-blind, placebo-controlled study, 39 hypertensive and 49 healthy individuals were randomized to receive high-dose vitamins (2 g vitamin C and 800IU vitamin E) or placebo followed by methionine loading 100 mg/kg body weight. Endothelium-dependent dilation (EDD) and endothelium-independent dilation (EID) of the brachial artery were evaluated by plethysmography, at baseline and 4 h postloading (4 h PML). ET-1 was measured by ELISA, whereas total lipid hydroperoxides (per-ox) levels were measured by a commercially available photometric technique. RESULTS: Acute, methionine-induced homocysteinemia decreased EDD in all study groups (P < 0.001 for all), whereas vitamins pretreatment failed to prevent this effect, despite the vitamins-induced reduction of peroxidation in the hypertensives group (P < 0.05). On the contrary, methionine loading significantly increased plasma ET-1 levels only in hypertensives (P < 0.05), an effect which was not prevented by antioxidant vitamins (P < 0.05). EID remained unchanged after methionine loading, in all study groups (P = NS for all groups). CONCLUSION: Experimental homocysteinemia rapidly blunts endothelial function in both hypertensive individuals and healthy individuals. The rapid elevation of ET-1 levels observed only in hypertensives, suggests that ET-1 may be the key mediator of homocysteine-induced endothelial dysfunction, independently of oxidative stress.

Managing hypertension in obstructive sleep apnea: the interplay of continuous positive airway pressure, medication and chronotherapy.

Hypertension is highly prevalent and usually uncontrolled among patients with obstructive sleep apnea despite multiple interventions, namely lifestyle modifications, use of antihypertensive drugs and continuous positive airway pressure application. Main prognosticators of the blood pressure (BP) reduction with continuous positive airway pressure therapy are high levels of BP, severity of apnea and daytime sleepiness. The long-term effect of continuous positive airway pressure on BP is still inconclusive, and compliance issues constitute a major limitation. There is no clear evidence for preference for a specific type of antihypertensive drug, and selection should primarily be guided by the patient's cardiometabolic profile and associated clinical conditions. Furthermore, as hypertensive patients with obstructive sleep apnea frequently exhibit a disturbed circadian BP pattern, chronotherapy emerges as a possible therapeutic supplement.

Early initiation of low-dose atorvastatin treatment after an acute ST-elevated myocardial infarction, decreases inflammatory process and prevents endothelial injury and activation.

BACKGROUND: High-dose statin treatment improves clinical outcome of ST-elevated myocardial infarction (STEMI). However, the effect of low-dose atorvastatin treatment on inflammatory and pro-thrombotic molecules during the post-STEMI period is unclear. We investigated the effect of low-dose atorvastatin treatment on the kinetics of cytokine IL-6, vascular cell adhesion molecule (sVCAM-1) and endothelium-derived markers of thrombosis/fibrinolysis such as von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA), post STEMI. METHODS: Twenty-four normocholesterolemic patients with STEMI were randomised to receive atorvastatin 10mg/day or no statin treatment for 6 weeks after the event. Blood samples were obtained by their admission to the hospital as well as at weeks 1 and 6. Circulating levels of IL-6, sVCAM-1, vWF, PAI-1 and tPA were determined by ELISA. RESULTS: Atorvastatin induced a decrease of IL-6 at 1 week, an effect which reached significance compared to baseline at 6 weeks post STEMI (p<0.05 vs baseline). Serum sVCAM-1 was increased in controls both at 1 and 6 weeks post-STEMI (p<0.05 vs baseline), an effect prevented by atorvastatin. Plasma vWF was increased 1 week post-STEMI in controls (p<0.05 vs baseline) and returned to baseline at 6 weeks, an effect prevented by atorvastatin. Plasma PAI-1, tPA and the PAI-1/tPA ratio remained unchanged in both groups. CONCLUSION: Early initiation of low-dose atorvastatin treatment decreases the expression of IL-6 and sVCAM-1 and the release of vWF in patients with STEMI. Therefore, low-dose atorvastatin, modulates inflammatory response and decreases endothelial injury and activation in patients with recent STEMI.

Effects of antioxidant vitamins C and E on endothelial function and thrombosis/fibrinolysis system in smokers.

Smoking is associated with endothelial dysfunction and abnormalities in thrombosis/fibrinolysis system, possibly through increased oxidative stress. In this study we investigated the effect of combined antioxidant treatment with vitamins C and E on endothelial function and plasma levels of plasminogen activator inhibitor (PAI-1), von Willebrand factor (vWF), tissue plasminogen activator (tPA) and factor VII (fVII), in smokers. Forty-one healthy smokers were randomly divided into 4 groups receiving vitamin C 2g/day (group A), vitamin C 2g/day plus vitamin E 400 IU/day (group B), vitamin C 2g/day plus vitamin E 800 IU/day (group C) or no antioxidants (controls, group D), for 4 weeks. Forearm blood flow was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to sublingual nitroglycerin administration (NTG%) were considered as indexes of endothelium dependent or independent dilation respectively. After treatment, RH% was increased only in groups B (p <0.05) and C (p <0.001) but not in groups A and D. Plasma levels of PAI-1 and vWF were decreased only in group C (p <0.05 for both), while PAI-1/tPA ratio was significantly decreased in both groups B and C (p <0.05 for both). NTG% and plasma levels of tPA and fVII remained invariable in all groups. In conclusion, combined administration of vitamin C and vitamin E at high dosages, improved endothelial function and decreased plasma levels of PAI-1, vWF and PAI-1/tPA ratio in chronic smokers.

Exaggerated carotid sinus massage responses are related to severe coronary artery disease in patients being evaluated for chest pain.

BACKGROUND: Previous studies have reported that carotid sinus massage responses are associated with advancing age and carotid or coronary artery disease. HYPOTHESIS: This study was undertaken to investigate the potential role of carotid sinus hypersensitivity as a marker for the presence of coronary artery disease, and especially left main stem disease, in patients who were referred for evaluation of chest pain. METHODS: Toward this end, carotid sinus stimulation with simultaneous recordings of the electrocardiogram and aortic pressure was performed before coronary arteriography in 150 selected consecutive patients (mean age 59.4+/-9 years) who were referred for evaluation of chest pain. RESULTS: Coronary artery disease was present in 118 patients (78.7%); of these, 35 had single-vessel disease, 35 had double-vessel disease, 33 had triple-vessel disease, and 15 had left main stem with or without such vessel disease. Carotid sinus hypersensitivity was found in 40 patients (26.6%). The incidence of hypersensitivity in patients with single-, double-, or triple-vessel disease and left main stem disease was 8.5, 14.2, 57.5, and 73.3%, respectively. Stepwise multiple logistic regression analysis revealed that left main stem disease was significantly and independently related to the presence of carotid sinus hypersensitivity (p < 0.05). In addition, the presence of hypersensitivity had 73.3% sensitivity, 86.2% specificity, and 96.3% negative predictive value for the presence of left main stem disease. CONCLUSION: In patients being evaluated for suspected ischemic heart disease, carotid sinus massage responses are related to severe coronary disease. The absence of hypersensitivity may reflect absence of left main stem disease.