Einfluss antihypertensiver Medikamente auf die Endothelfunktion

Zusammenfassung: Bei Patienten mit arterieller Hypertonie liegt eine Endotheldysfunktion vor. Eine reduzierte Verfügbarkeit von gefäßerweiterndem Stickstoffmonoxid (NO) sowie ein Überschuss an vasokonstriktiven Substanzen (z.B. Endothelin oder Angiotensin II) sind als Ursache der gestörten endothelabhängigen Vasodilatation anzusehen. Das Vorhandensein einer Endotheldysfunktion korreliert mit kardiovaskulären Ereignissen und hat auch prognostische Bedeutung. Die Reduktion des Blutdrucks per se ist nicht ausreichend, um die Endothelfunktion zu verbessern. Die verschiedenen Substanzklassen der Antihypertensiva beeinflussen die Gefäßfunktion in unterschiedlicher Art und Weis

Interactions between sympathetic nervous system and endogenous endothelin in patients with essential hypertension

Experimental evidence indicates that endothelin 1 stimulates the sympathetic nervous system by activation of the subtype A receptor. The aim of the present study was to assess whether this mechanism is active in humans and to investigate its potential role in the pathogenesis of essential hypertension. In 15 hypertensive patients and 12 normotensive subjects, blood pressure, heart rate, and muscle sympathetic nerve activity were evaluated during intravenous 20-minute infusion of BQ123 (0.1 mg/kg per hour), an endothelin A receptor antagonist, and sodium nitroprusside (SNP; 0.4 μg/kg per minute). In hypertensive patients, blood pressure was reduced similarly by BQ123 and SNP. In contrast, the increase in muscle sympathetic nerve activity induced by BQ123 (from 52.0±4.9 to 56.8±5.5 bursts per 100 heartbeats; P<0.05 versus baseline) was significantly lower (P<0.05) than that induced by SNP (from 50.6±4.9 to 61.1±5.1 bursts per 100 heartbeats; P<0.05 versus baseline). In normotensive subjects, SNP reduced blood pressure and increased muscle sympathetic activity, whereas BQ123 was ineffective. Thus, in a subgroup (n=9) of normotensive subjects, we administered BQ123 at a higher dose (0.2 mg/kg per hour), representing an equidepressor dose of SNP, inducing a blunted increase in sympathetic activity (from 44.1±2.4 to 50.1±6.4 bursts per 100 heartbeats; P<0.05 versus baseline). Finally, administration of a different vasodilator (papaverine, 0.5 mg/kg per hour) exerted results superimposable to SNP. Endogenous endothelin 1 appears to have a sympathoexcitatory effect both in normotensive and hypertensive subjects through endothelin A receptors, contributing to basal sympathetic vasomotor tone. Moreover, essential hypertension shows an increased susceptibility to the sympathoexcitatory effect of endogenous endothelin 1

Acute effect of nitroglycerin on cyclosporine-induced hypertension after cardiac transplantation

BACKGROUND: Cyclosporine represents a milestone in immunosuppression following organ transplantation. Its use, however, comes at the cost of significant side effects, such as arterial hypertension which is rarely controllable by currently available anti-hypertensive drugs. The aim was to investigate the effect of acute administration of nitroglycerin in heart-transplanted patients with cyclosporine-induced hypertension. METHODS: The sample included 18 cyclosporine-induced hypertensive patients (HTX group) scheduled for elective cardiac catheterization following heart transplantation, as well as 6-matched essential hypertensive patients (HT group). The blood pressure (BP) in the aorta and pulmonary artery, before and after administration of nitroglycerin, was measured simultaneously. RESULTS: After injection of 50 microg and 100 microg nitroglycerin, BP significantly decreased both in HTX (systolic (s) BP p = 0.0001; diastolic (d) BP p = 0.0001) and in controls (sBP p = 0.006; dBP p = 0.05). This reduction was more pronounced in HTX (sBP p = 0.022; dBP p = 0.018 for group-comparison). Following analysis of the data in relation to its individual baseline, a significantly higher reduction of the BP induced by 100 microg nitroglycerin was observed in the HTX group compared to the HT group (p = 0.02 for sBP and p = 0.03 for dBP). 8 +/- 3 minutes after the last nitrate infusion, BP remained significantly reduced compared to baseline in HTX (p <0.001), whereas it came back to baseline in controls. The reduction in sBP was correlated to cyclosporine A levels (p = 0.04 after 50microg nitroglycerin; p = 0.05 after 100 microg nitroglycerin). CONCLUSION: After application of nitroglycerin, sBP is reduced immediately in HTX with uncontrolled cyclosporine-induced hypertension. Further studies are needed to evaluate the long-term effect of nitrates in these patients

Chronic treatment with long-acting nifedipine reduces vasoconstriction to endothelin-1 in essential hypertension

Essential hypertension is associated with enhanced biological activity of endothelin-1 (ET-1) and impaired endothelium-dependent vasodilatation. Dihydropyridine calcium antagonists have antioxidant activity in vitro, and they improve endothelial function in vivo. We tested whether calcium antagonists also influence the biological activity of ET-1 in essential hypertensive (EH) patients in the presence and absence of hypercholesterolemia. In 9 healthy subjects (normotensive [NT] subjects, age: 48.3+/-7.6 years; blood pressure: 118+/-8.6/69+/-5.4 mm Hg) and 21 EH subjects (age: 50.0+/-7.8 years; blood pressure: 164.4+/-5.4/103.8+/-4.4 mm Hg), we studied forearm blood flow and its modification induced by intrabrachial administration of ET-1, phenylephrine, acetylcholine, and sodium nitroprusside at baseline and after 24 weeks of treatment with a nifedipine gastrointestinal therapeutic system (30 to 60 mg per day). At baseline, the first dose of ET-1 (0.5 microg/100 mL of forearm tissue per minute) caused a slight vasodilatation in NT but not in EH subjects, whereas the following higher doses caused a comparable dose-dependent vasoconstriction in EH and NT subjects. The effect of acetylcholine was significantly reduced in EH as compared with NT subjects. In contrast, sodium nitroprusside and phenylephrine had similar effects in NT and EH subjects. After chronic treatment with the nifedipine gastrointestinal therapeutic system, the vasoconstrictor effect induced by both ET-1 and phenylephrine was significantly blunted, whereas the response to acetylcholine was significantly increased and the vasodilation to sodium nitroprusside unchanged. Hypercholesterolemic EH subjects showed a further reduced response to acetylcholine compared with normocholesterolemic EH subjects, and the nifedipine gastrointestinal therapeutic system restored the vasodilation to acetylcholine in this subgroup. In conclusion, in EH subjects, chronic treatment with a long-acting dihydropyridine calcium antagonist not only exhibits a blood pressure-lowering effect but also reduces ET-1-induced vasoconstriction and improves endothelium-dependent vasodilation. Those vasculoprotective effects may importantly contribute to a reduction in major clinical events seen during treatment with these compound

Spontanous periodic breathing is associated with sympathetic hyperreactivity and baroreceptor dysfunction in hypertension

OBJECTIVES: Intermittent periods of hypoxemia such as during periodic breathing are associated with hypertension and increased sympathetic activity. In patients with sleep apnea syndrome, hypertension is common. Treating apnea improves hypertension and reduces sympathetic outflow. The aim of the present study was to investigate the phenomenon and mechanisms of spontaneous periodic breathing in patients with hypertension. METHOD: We examined 43 hypertensive patients with untreated hypertension without left-ventricular dysfunction, heart failure or sleep apnea syndrome. Muscle sympathetic nerve activity (MSA), heart rate (HR), blood pressure (BP) and respiration were continuously recorded at rest and during cold-pressor testing. Oxygen and a CO2-enriched gas were used to test central and peripheral chemoreceptors, respectively. Baroreceptor gain was measured using the alpha method. RESULTS: Seven out of 43 patients showed spontaneous periodic breathing while awake. No difference in MSA, HR and BP was seen between patients with and without periodic breathing at rest except the breathing pattern. However, the cold-pressor test caused a larger increase of MSA in patients with periodic breathing (203 +/- 62 vs. 62 +/- 8%, P < 0.0001 by ANOVA), as well as systolic (46 +/- 6 vs. 25 +/- 3 mmHg, P = 0.002) and diastolic BP (26 +/- 5 vs. 12 +/- 1 mmHg, P = 0.004, ANOVA). Baroreceptor gain was markedly higher in patients with periodic breathing. Chemoreceptor sensitivity was comparable. CONCLUSION: Spontaneous periodic breathing is relatively common in patients with hypertension and is associated with greatly enhanced responses to cold-pressor testing. We suggest increased baroreceptor gain and sympathetic outflow as a cause for the oscillatory respiration pattern via barorespiratory coupling

Renale Denervation: Schweizer Erfahrungen im Langzeitverlauf

Despite great advances in pharmacological and non-pharmacological treatment of patients with arterial hypertension, a significant proportion of patients do not reach the target values suggested by the guidelines. A therapy-resistant hypertension is defined as a blood pressure above the suggested target values despite an antihypertensive therapy with three medications at maximal dosis, including a diuretic. The renal denervation is a new and promising method for the treatment of refractory arterial hypertension. An optimal selection of the patients undergoing a renal denervation is extremely important, and this intervention should be performed in highly specialized centers only

Effect of Home Blood Pressure Monitoring on Patient's Awareness and Goal Attainment Under Antihypertensive Therapy: The Factors Influencing Results in Anti-HypertenSive Treatment (FIRST) Study.

Despite availability of a broad spectrum of blood pressure (BP)-lowering drugs many hypertensive patients do not attain BP goals. We aimed to evaluate the influence of home blood pressure monitoring (HBPM) on patient's awareness and attainment of BP goals under antihypertensive treatment with irbesartan alone or in combination with hydro-chlorothiazide. In total, 1,268 patients with arterial hypertension were enrolled in the Factors Influencing Results in anti-hypertenSive Treatment (FIRST) study by 348 general practitioners and internal medicine specialists across Switzerland. Patients selected for HBPM received detailed information and training on BP self-management. The study endpoints included patient's awareness and attainment of BP goals, and the efficacy and tolerability of antihypertensive treatment at 3 months. Overall, the mean age was 61±13 years and 616 (49%) were women. The mean systolic/diastolic BP was 161±17/96±11 mmHg, and 239 (19%) patients had diabetes mellitus. 758 (60%) patients were instructed to use HBPM. Both the proportion of patients aware of their BP goals (81% vs. 70%; p&lt; 0.001) and the percentage of patients reaching their BP goal (64% vs. 57%; p=0.028) were higher in those with vs. without HBPM. The mean reduction in systolic/diastolic BP was 23.8/13.2 mmHg. Only 35 (3.0%) patients discontinued antihypertensive therapy. In a large Swiss cohort of patients with arterial hypertension, information and training on BP self-measurement and direct involvement of patients by using HBPM led to improvement in BP control. Treatment with irbesartan alone or in combination with hydrochlorothiazide was well tolerated and markedly reduced BP

Global Symmetries and D-Terms in Supersymmetric Field Theories

We study the role of D-terms in supersymmetry (SUSY) breaking. By carefully analyzing the SUSY multiplets containing various conserved currents in theories with global symmetries, we obtain a number of constraints on the renormalization group flow in supersymmetric field theories. Under broad assumptions, these results imply that there are no SUSY-breaking vacua, not even metastable ones, with parametrically large D-terms. This explains the absence of such D-terms in models of dynamical SUSY-breaking. There is, however, a rich class of calculable models which generate comparable D-terms and F-terms through a variety of non-perturbative effects; these D-terms can be non-abelian. We give several explicit examples of such models, one of which is a new calculable limit of the 3-2 model.Comment: 34 pages, 2 figures; reference added, minor change

Sex differences in arterial hypertension.

There is strong evidence that sex chromosomes and sex hormones influence blood pressure (BP) regulation, distribution of cardiovascular (CV) risk factors and co-morbidities differentially in females and males with essential arterial hypertension. The risk for CV disease increases at a lower BP level in females than in males, suggesting that sex-specific thresholds for diagnosis of hypertension may be reasonable. However, due to paucity of data, in particularly from specifically designed clinical trials, it is not yet known whether hypertension should be differently managed in females and males, including treatment goals and choice and dosages of antihypertensive drugs. Accordingly, this consensus document was conceived to provide a comprehensive overview of current knowledge on sex differences in essential hypertension including BP development over the life course, development of hypertension, pathophysiologic mechanisms regulating BP, interaction of BP with CV risk factors and co-morbidities, hypertension-mediated organ damage in the heart and the arteries, impact on incident CV disease, and differences in the effect of antihypertensive treatment. The consensus document also highlights areas where focused research is needed to advance sex-specific prevention and management of hypertension