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

Higgs Messengers

We explore the consequences of the Higgs fields acting as messengers of supersymmetry breaking. The hidden-sector paradigm in the gauge mediation framework is relaxed by allowing two types of gauge-invariant, renormalizable operators that are typically discarded: direct coupling between the Higgses and supersymmetry breaking singlets, and Higgs-messenger mixing terms. The most important phenomenological consequence is a flavor-dependent shift in sfermion masses. This is from a one-loop contribution, which we compute for a general set of weak doublet messengers. We also study a couple of explicit models in detail, finding that precision electroweak constraints can be satisfied with a spectrum significantly different from that of gauge mediation.Comment: 20 pages, 5 figure

Surveying Pseudomoduli: the Good, the Bad and the Incalculable

We classify possible types of pseudomoduli which arise when supersymmetry is dynamically broken in infrared-free low-energy theories. We show that, even if the pseudomoduli potential is generated only at higher loops, there is a regime where the potential can be simply determined from a combination of one-loop running data. In this regime, we compute whether the potential for the various types of pseudomoduli is safe, has a dangerous runaway to the UV cutoff of the low-energy theory, or is incalculable. Our results are applicable to building new models of supersymmetry breaking. We apply the results to survey large classes of models.Comment: 34 page

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

On a modular property of N=2 superconformal theories in four dimensions

In this note we discuss several properties of the Schur index of N=2 superconformal theories in four dimensions. In particular, we study modular properties of this index under SL(2,Z) transformations of its parameters.Comment: 23 page, 2 figure

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

Testing the Nambu-Goldstone Hypothesis for Quarks and Leptons at the LHC

The hierarchy of the Yukawa couplings is an outstanding problem of the standard model. We present a class of models in which the first and second generation fermions are SUSY partners of pseudo-Nambu-Goldstone bosons that parameterize a non-compact Kahler manifold, explaining the small values of these fermion masses relative to those of the third generation. We also provide an example of such a model. We find that various regions of the parameter space in this scenario can give the correct dark matter abundance, and that nearly all of these regions evade other phenomenological constraints. We show that for gluino mass ~700 GeV, model points from these regions can be easily distinguished from other mSUGRA points at the LHC with only 7 fb^(-1) of integrated luminosity at 14 TeV. The most striking signatures are a dearth of b- and tau-jets, a great number of multi-lepton events, and either an "inverted" slepton mass hierarchy, narrowed slepton mass hierarchy, or characteristic small-mu spectrum.Comment: Corresponds to published versio

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

General Gauge Mediation with Gauge Messengers

We generalize the General Gauge Mediation formalism to allow for the possibility of gauge messengers. Gauge messengers occur when charged matter fields of the susy-breaking sector have non-zero F-terms, which leads to tree-level, susy-breaking mass splittings in the gauge fields. A classic example is that SU(5) / SU(3) x SU(2) x U(1) gauge fields could be gauge messengers. We give a completely general, model independent, current-algebra based analysis of gauge messenger mediation of susy-breaking to the visible sector. Characteristic aspects of gauge messengers include enhanced contributions to gaugino masses, (tachyonic) sfermion mass-squareds generated already at one loop, and also at two loops, and significant one-loop A-terms, already at the messenger scale.Comment: 79 pages, 5 figure

Simplified R-Symmetry Breaking and Low-Scale Gauge Mediation

We argue that some of the difficulties in constructing realistic models of low-scale gauge mediation are artifacts of the narrow set of models that have been studied. In particular, much attention has been payed to the scenario in which the Goldstino superfield in an O'Raifeartaigh model is responsible for both supersymmetry breaking and R-symmetry breaking. In such models, the competing problems of generating sufficiently massive gauginos while preserving an acceptably light gravitino can be quite challenging. We show that by sharing the burdens of breaking supersymmetry and R-symmetry with a second field, these problems are easily solved even within the O'Raifeartaigh framework. We present explicit models realizing minimal gauge mediation with a gravitino mass in the eV range that are both calculable and falsifiable.Comment: 31 pages, 4 figures, references added, minor change