Dionysios Adamopoulos

Acute Effects of Passive Smoking on Peripheral Vascular Function

Environmental tobacco smoke (ETS) acutely affects peripheral and coronary vascular tone. Whether ETS exerts specific deleterious effects on aortic wave reflection through nicotine exposure, whether they persist after ETS cessation, and whether the smoke environment impairs microvascular function and increases asymmetrical dimethyl-arginine levels are not known. We tested these hypotheses in a randomized, crossover study design in 11 healthy male nonsmokers. The effects of 1 hour of exposure to ETS, as compared with a nontobacco smoke and normal air, on augmentation index corrected for heart rate and skin microvascular hyperemia to local heating were examined. Augmentation index increased both during (P=0.01) and after (P<0.01) the ETS session but remained unchanged in the nontobacco smoke session when compared with normal air. Nicotine levels after the exposure were related to the peak rise in augmentation index (r=0.84; P<0.01), denoting a predominant role of nicotine in ETS vascular effects. This was confirmed in a second set of experiments (n=14), where the sublingual administration of nicotine was associated with an acute impairment in wave reflection as compared with placebo (P=0.001). Both ETS and nontobacco smokes increased plasma asymmetrical dimethyl-arginine levels (P<0.001), but only ETS reduced the late rise in skin blood flow in response to heating (P=0.03). In conclusion, passive smoking specifically increases aortic wave reflection through a nicotine-dependent pathway and impairs microvascular function, even after the end of the exposure. However, both tobacco and nontobacco passive smoking inhalation increase plasma asymmetrical dimethyl-arginine levels.

NEW INSIGHTS INTO THE SYMPATHETIC, ENDOTHELIAL AND CORONARY EFFECTS OF NICOTINE

1 Nicotine is a well studied pleiotropic agent which occurs naturally in tobacco smoke and has been largely accused for many of the adverse effects of smoking on the cardiovascular system, including autonomic imbalance, endothelial dysfunction and coronary blood flow dysregulation. 2 The acute sympathoexcitatory effects of smoking on the cardiovascular system are partially mediated by catecholamine release, muscle sympathetic nerve excitation and peripheral chemoreceptor sensitivity increase, consecutive to nicotinic receptor stimulation in the autonomic nervous system. 3 Recent animal data suggest that nicotine promotes the oxidative and inflammatory stress to the endothelium and induces pathological angiogenesis, leading to the progression of the atherosclerotic lesions. 4 Nicotine increases myocardial work without impairing the physiological coronary vasodilatation. Consequently, nicotine per se cannot explain the sudden reduction in coronary flow reserve after exposure to both active and passive smoking. 5 Nicotines biological effects are characterized by a rapid onset of tolerance, which can explain why nicotine administration does not elicit acute coronary and chemoreflex side‐effect in smokers.

Validation of the Microlife WatchBP Home device for self home blood pressure measurement according to the International Protocol.

ObjectiveCurrent guidelines recommend that only validated devices for blood pressure measurement should be used. This study presents the validation results of the Microlife BPA100 Plus monitor for self-home blood pressure measurement, according to the European Society of Hypertension International Protocol. MethodsFifteen study participants were included in phase 1 and an additional 18 in phase 2 (total 33). Simultaneous blood pressure measurements were taken by two trained observers (Y tube connected mercury sphygmomanometers) four times, sequentially with three measurements taken using the tested device. Absolute differences between observer and device blood pressure were classified into three zones (within 5, 10 and 15 mmHg). The number of readings with a difference within 5 mmHg was calculated for each individual. ResultsIn phase 1, the device produced 32, 42 and 43 measurements within 5, 10 and 15 mmHg, respectively, for systolic blood pressure and 31, 45 and 45 for diastolic blood pressure. In phase 2.1, the device produced 71, 87 and 96 measurements within 5, 10 and 15 mmHg, respectively, for systolic blood pressure, and 71, 98 and 99 measurements for diastolic blood pressure. In phase 2.2, 26 participants had at least two of their differences within 5 mmHg and three participants had no differences within 5 mmHg for systolic blood pressure, whereas for diastolic blood pressure 24 and three participants, respectively. Mean systolic blood pressure differences were −2.0±6.0 mmHg and diastolic blood pressure differences were −3.1±4.1 mmHg. ConclusionsThe Microlife BPA100 Plus device for self-home blood pressure measurement comfortably passes the validation requirements of the International Protocol and therefore can be recommended for clinical use in the adult population.

Acute effect of sidestream cigarette smoke extract on vascular endothelial function.

Acute exposure to passive smoking adversely affects vascular function by promoting oxidative stress and endothelial dysfunction. However, it is not known whether tobacco sidestream (SS) smoke has a greater deleterious effect on the endothelium than non-tobacco SS smoke and whether these effects are related to nicotinic endothelial stimulation. To test these hypotheses, endothelial-dependent relaxation and superoxide anion production were assessed in isolated rat aortas incubated with tobacco SS smoke, non-tobacco SS smoke, or pure nicotine. Tobacco SS smoke decreased the maximal relaxation to acetylcholine (Ach) from 79 ± 6% to 57 ± 7.3% (% inhibition of phenylephrine-induced plateau, P < 0.001) and increased superoxide anion production from 31 ± 9.7 to 116 ± 24 count/10sec/mg (P < 0.01, lucigenin-enhanced chemiluminescence technique). The non-tobacco SS smoke extract had no significant effect on the response to Ach but increased superoxide anion production in the aortic wall to 133 ± 2 count/10sec/mg (P < 0.001). Furthermore, concentration-response curves to Ach and superoxide production remained unaltered with nicotine (0.001, 0.01, or 0.1 mM). In conclusion, despite similar increases in vascular wall superoxide production with tobacco and non-tobacco SS smoke, only the tobacco SS smoke extracts affected endothelium-dependent vasorelaxation. Nicotine alone does not reproduce the effects seen with tobacco SS smoke, suggesting that the acute endothelial toxicity of passive smoking cannot simply be ascribed to a nicotine-dependent mechanism.

Nocturnal blood pressure fall and metabolic syndrome score in hypertensive patients.

BackgroundData relating dipping status to metabolic syndrome (MS) scores are not available. The purpose of this study is to investigate any possible association of different dipping patterns to MS scores in untreated patients with essential hypertension. MethodsThe study included 6256 consecutive, treatment-naive patients with essential hypertension who attended our outpatient clinics. All underwent repeated office blood pressure measurements, 24-h ambulatory blood pressure monitoring, and full clinical and laboratory evaluation. The diagnosis of MS was made according to the Adult Treatment Panel III criteria and patients were classified into five groups: group I (hypertension), group II (hypertension+any one component), group III (hypertension+any two components), group IV (hypertension+any three components), and group V (all five components). Dipping pattern was defined as ‘dippers’ with nocturnal systolic blood pressure (NSBP) falling ≥10 but <20%, ‘nondippers’ with NSBP falling ≥0% but <10%, ‘extreme dippers’ with NSBP falling ≥20%, and ‘reverse dippers’ with NSBP increasing. ResultsHypertensive patients with MS (n=2573) had higher clinical and ambulatory blood pressure values (P<0.001), whereas the dominant dipping pattern in the non-MS group was nondippers (47.6%), and in the MS group, extreme dippers (37.8%). Furthermore, a considerable decrease in the prevalence of dippers was noticed with the increasing number of MS components (21.1 vs. 19.2 vs. 14.5 vs. 8.4 vs. 7.2%, P<0.001). In contrast, a significant rise in the prevalence of reverse dippers was observed with the increasing number of MS components (7.4 vs. 10.1 vs. 14.9 vs. 20.4 vs. 31.2%, P<0.001). ConclusionsIt seems that hypertensive patients have an increased prevalence of abnormal dipping patterns as the number of MS components rises.

Beta-adrenergic blockade and metabo-chemoreflex contributions to exercise capacity.

PURPOSE Exercise-induced dyspnea in patients with cardiopulmonary diseases may be related to sympathetic nervous system activation, with increased metabo- and/or chemosensitivities. Whether this mechanism plays a role in exercising normal subjects remains unclear. METHODS Muscle sympathetic nerve activity (MSNA), HR, ventilation (V(E)), O2 saturation (SpO2), and end-tidal PCO2 (PetCO2) were measured in 14 healthy young adults after 1 wk of beta1-receptor blockade with bisoprolol 5 mg x d(-1) versus placebo after a double-blind, placebo-controlled, randomized crossover design. The MSNA and the ventilatory responses to hyperoxic hypercapnia (7% CO2 in O2), DeltaV(E)/DeltaPetCO2, and isocapnic hypoxia (10% O2 in N2), DeltaV(E)/DeltaSpO2, and to an isometric muscle contraction followed by a local circulatory arrest (metaboreflex) were determined at rest followed by an incremental cardiopulmonary exercise test. RESULTS Bisoprolol did not change the V(E) and MSNA responses to hypercapnia, hyperoxia, or isometric muscle contraction or ischemia. Bisoprolol decreased maximum O2 uptake (P < 0.05), workload (P < 0.05), and HR (P < 0.0001) and both V(E)/VO2 and V(E)/VCO2 slopes (P < 0.05). CONCLUSIONS These results suggest that decreased aerobic exercise capacity after intake of beta-blockers is accompanied by decreased ventilation at any metabolic rate. However, this occurs without detectable change in the sympathetic nervous system tone or in metabo- or chemosensitivity and is therefore probably of hemodynamic origin.

Differential effects of metaboreceptor and chemoreceptor activation on sympathetic and cardiac baroreflex control following exercise in hypoxia in human.

Muscle metaboreceptors and peripheral chemoreceptors exert differential effects on the cardiorespiratory and autonomic responses following hypoxic exercise. Whether these effects are accompanied by specific changes in sympathetic and cardiac baroreflex control is not known. Sympathetic and cardiac baroreflex functions were assessed by intravenous nitroprusside and phenylephrine boluses in 15 young male subjects. Recordings were performed in random order, under locally circulatory arrested conditions, during: (1) rest and normoxia (no metaboreflex and no chemoreflex activation); (2) normoxic post‐handgrip exercise at 30% of maximum voluntary contraction (metaboreflex activation without chemoreflex activation); (3) hypoxia without handgrip (10% O2 in N2, chemoreflex activation without metaboreflex activation); and (4) post‐handgrip exercise in hypoxia (chemoreflex and metaboreflex activation). When compared with normoxic rest (−42 ± 7% muscle sympathetic nerve activity (MSNA) mmHg−1), sympathetic baroreflex sensitivity did not change during normoxic post‐exercise ischaemia (PEI; −53 ± 9% MSNA mmHg−1, P= 0.5) and increased during resting hypoxia (−68 ± 5% MSNA mmHg−1, P < 0.01). Sympathetic baroreflex sensitivity decreased during PEI in hypoxia (−35 ± 6% MSNA mmHg−1, P < 0.001 versus hypoxia without exercise; P= 0.16 versus normoxic PEI). Conversely, when compared with normoxic rest (11.1 ± 1.7 ms mmHg−1), cardiac baroreflex sensitivity did not change during normoxic PEI (8.3 ± 1.3 ms mmHg−1, P= 0.09), but decreased during resting hypoxia (7.3 ± 0.8 ms mmHg−1, P < 0.05). Cardiac baroreflex sensitivity was lowest during PEI in hypoxia (4.3 ± 1 ms mmHg−1, P < 0.01 versus hypoxia without exercise; P < 0.001 versus normoxic exercise). The metaboreceptors and chemoreceptors exert differential effects on sympathetic and cardiac baroreflex function. Metaboreceptor activation is the major determinant of sympathetic baroreflex sensitivity, when these receptors are stimulated in the presence of hypoxia.

Acute effects of nicotine on arterial stiffness and wave reflection in healthy young non-smokers.

1 Recently, we have demonstrated that cigarette smoke exposure proportionally increases plasma nicotine levels and arterial wave reflection to the aorta. However, the exact contribution of nicotine to the smoke‐induced enhancement of wave reflection and the potential underlying mechanisms have not been fully investigated. 2 The present study was a prospective study in 15 healthy male non‐smokers. All received a placebo and a 2 mg nicotine tablet, according to a randomized double‐blind cross‐over study design. Each subject underwent repeated measurements at baseline and for 1 h after nicotine or placebo intake, using carotid–femoral pulse wave velocity (PWV) to assess arterial compliance. Concurrently, aortic pressures and the augmentation index were evaluated using applanation tonometry. 3 Plasma nicotine concentrations achieved 1 h after intake of the nicotine tablet reached comparable levels to those achieved after 1 h exposure to passive smoke (3.6 ± 0.4 vs 3.2 ± 0.4 ng/mL, respectively; P = 0.4). 4 Nicotine enhanced arterial wave reflection to the aorta, as assessed by the augmentation index corrected for heart rate (4.2 ± 1.3 vs–0.7 ± 0.8% with placebo; P = 0.001). In addition, a progressive increase in carotid–femoral PWV was noted after nicotine administration (0.3 ± 0.1 vs–0.02 ± 0.1 m/s with placebo; P = 0.04). This remained significant even after adjustment for changes in mean blood pressure and heart rate (P = 0.01). 5 Plasma nicotine concentrations comparable to those achieved after exposure to passive smoke enhance arterial wave reflection to the aorta. This is accompanied by an increase in carotid–femoral PWV, denoting a deterioration of arterial compliance by nicotine.

Nicotine increases chemoreflex sensitivity to hypoxia in non-smokers.

Background The peripheral chemoreflex contributes to cardiovascular regulation and represents the first line of defence against hypoxia. The effects of nicotine on chemoreflex regulation in non-smoking humans are unknown. Method We conducted a prospective, randomized, crossover, and placebo-controlled study in 20 male non-smokers to test the hypothesis that nicotine increases chemoreflex sensitivity. The effects of two intakes of 2 mg nicotine tabs and placebo on sympathetic nerve activity to muscle circulation (muscle sympathetic nerve activity; MSNA), minute ventilation (Ve), blood pressure and heart rate were assessed during normoxia, moderate isocapnic hypoxia, hyperoxic hypercapnia and an isometric handgrip in 10 subjects. Maximal end-expiratory apnoeas were performed at baseline and at the end of the fifth minute of hypoxia. In a second experimental setting, we studied the ventilatory response to a more marked isocapnic hypoxia in 10 other volunteers. Results Mean MSNA and Ve were not modified by nicotine during the 5 min of normoxia or moderate hypoxia. In the presence of nicotine MSNA was related to oxygen desaturation (P < 0.01). The sympathoexcitatory effects of nicotine became especially evident when apnoeas achieved oxygen saturations less than 85% (511 ± 44% increase in MSNA after the first intake, and 436 ± 43% increase after the second intake versus 387 ± 56% and 338 ± 31% with placebo, respectively, P < 0.05). Nicotine also increased the ventilatory response compared with placebo when oxygen saturation decreased to less than 85% (P < 0.05). Conclusion This is the first study to demonstrate that nicotine increases peripheral chemoreflex sensitivity to large reductions in arterial oxygen content in healthy non-smokers.

Nocturnal blood pressure fall and metabolic syndrome score in patients with white coat hypertension.

BackgroundAccumulating data report that white coat hypertension (WCH) is associated with target organ damage. Metabolic syndrome (MS), and nondipping pattern is also associated with increased cardiovascular risk. The purpose of this study was to explore the nocturnal blood pressure fall in WCH patients according to their MS score. MethodsThe study comprised 2300 patients with WCH who attended our outpatient clinics. All underwent repeated office blood pressure measurements, 24-h ambulatory blood pressure monitoring, full clinical and laboratory evaluation. The diagnosis of MS was made according to the Adult Treatment Panel III criteria and patients were classified into five groups: group I (hypertension), group II (hypertension and any one component), group III (hypertension and any two components), group IV (hypertension and any three components), and group V (all five components). Dipping pattern was defined as ‘dippers’ with nocturnal systolic blood pressure (NSBP) fall greater than or equal to 10% but less than 20%, ‘nondippers’ with NSBP fall greater than or equal to 0% but less than 10%, ‘extreme dippers’ with NSBP fall greater than or equal to 20%, and ‘reverse dippers’ with NSBP increase. ResultsPatients were divided into two groups according to the presence (n=522) and absence (n=1778) of MS. The overall prevalence of MS in the study population was 22.7%. Comparing the non-MS group with the MS we observed significant differences for nondippers (24.5% vs. 38.9%, P<0.001), dippers (54.4% vs. 43.5%, P<0.001), extreme dippers (17.8% vs. 11.3%, P<0.001), and reverse dippers (3.3% vs. 6.3%, P=0.007). ConclusionPatients with WCH and increased number of MS components present with elevated nighttime SBP levels. This observation is of a great significance in the assessment of the cardiovascular risk in these patients.