Direkte Reninhemmer oder Kirene

Zusammenfassung: Die direkten Reninhemmer (DRI) bilden eine neue Klasse blutdrucksenkender Arzneimittel. Wie die ACE-Hemmer und die Angiotensinrezeptorblocker (ARB) dämpfen sie das Renin-Angiotensin-Aldosteronsystem (RAAS). Als gut verträgliche und hochspezifische Therapeutika senken sie die Plasmaspiegel sämtlicher Angiotensine und dürften in Zukunft erfolgreich bei Herz-Kreislauf- und Nierenkrankheiten eingesetzt werden. DRI verursachen weder Husten noch Angioödeme, was sie vor den ACE-Hemmern auszeichnet. Auch metabolische Nebenwirkungen fehlen (keine Dyslipidämie, Hyperurikämie, Diabetes...). DRI können als Alternative oder als Kombinationspartner zu anderen RAAS-Blockern (ARB, ACE-Hemmern, β-Blockern, Aldosteronantagonisten), Kalziumantagonisten oder Diuretika werden verwendet. Aliskiren/Rasilez® ist ein erster lang wirksamer und gut verträglicher Reninhemmer, der als Monotherapie oder in Kombination mit anderen Antihypertensiva eingesetzt wir

Social uncertainty is heterogeneous and sometimes valuable

To win friends, help the needy, avoid exploitation or influence strangers, people must make decisions that are inherently uncertain. In their compelling and insightful perspective on resolving social uncertainty1, FeldmanHall and Shenhav (henceforth F&S) join a growing movement combining computational approaches with social psychological theory. F&S identify a range of negative and positive aspects of social uncertainty. Here we offer additional ways to think about social uncertainty and suggest potential avenues for future research

Plasma Angiotensin II and the Antihypertensive Action of Angiotensin-Converting Enzyme Inhibition

The measurement of immunoreactive "angiotensin II” in plasma cannot provide an accurate reflection of the efficacy of angiotensin-converting enzyme (ACE) inhibition because different angiotensin fragments interfere in all radioimmunoassays available so far. More complex methods are necessary in order to measure specifically angiotensin-(1-8)octapeptide. With such methodology it can be shown that no tolerance develops to the angiotensin II-reducing effect of ACE inhibitors after prolonged administration. Marked reduction of angiotensin II levels can be shown even in patients with primary aldosteronism. At peak blockade, the level of plasma angiotensin II is still related to circulating active renin and angiotensin I. Accordingly, because ACE inhibitors raise circulating angiotensin I in a dose-dependent fashion, this should be taken into account when dosing ACE inhibitors. The hypothesis that tissue renin-angiotensin systems play an important independent role in determining vasomotor tone is very interesting. However, any discussion on whether tissue or plasma renin determines the pharmacological effect of ACE inhibitors should be based on the simultaneous measurement of true angiotensin II in tissue and plasma under steady-state conditions. Am J Hypertens 1989;2:286-29

Dose-Response Relationships Following Oral Administration of DuP 753 to Normal Humans

We assessed the inhibitory effect of DuP 753, an orally active angiotensin II receptor antagonist, on the pressor action of exogenous angiotensin I and II in healthy volunteers. In a single dose study, doses of 2.5, 5, 10, 20, and 40 mg of DuP 753 or placebo were tested serially at one week intervals. In the multiple dose study, the administration of placebo or DuP 753 (5, 10, 20, or 40 mg, per os once daily) for eight consecutive days was evaluated. The blood pressure response to angiotensin I and II was inhibited in a dose-dependent fashion with a blocking effect still present 24 h post drug. DuP 753 also induced a dose-dependent compensatory rise in plasma renin. This new compound was well tolerated by these normal volunteers. Thus, DuP 753 appears to be a well tolerated, orally active, potent and long-lasting antagonist of angiotensin II in humans. Am J Hypertens 1991;4:350S-354

Uncertainty about the impact of social decisions increases prosocial behaviour

Uncertainty about how our choices will affect others infuses social life. Past research suggests uncertainty has a negative effect on prosocialbehaviour by enabling people to adopt self-serving narratives about their actions. We show that uncertainty does not always promote selfishness. We introduce a distinction between two types of uncertainty that have opposite effects on prosocial behaviour. Previous work focused on outcome uncertainty (uncertainty about whether or not a decision will lead to a particular outcome). However, as soon as people’s decisions might have negative consequences for others, there is also impact uncertainty (uncertainty about how others’ well-being will be impacted by the negative outcome). Consistent with past research, we found decreased prosocial behaviour under outcome uncertainty. In contrast, prosocial behaviour was increased under impact uncertainty in incentivized economic decisions and hypothetical decisions about infectious disease threats. Perceptions of social norms paralleled the behavioural effects. The effect of impact uncertainty on prosocial behaviour did not depend on the individuation of others or the mere mention of harm, and was stronger when impact uncertainty was made more salient. Our findings offer insights into communicating uncertainty, especially in contexts where prosocial behaviour is paramount, such as responding to infectious disease threats

Clinical Experience With Angiotensin II Receptor Antagonists

This series of studies was designed to assess in normal volunteers the relationships between various doses (5, 10, 20, 40, 80, and 120 mg) of the orally active angiotensin II antagonist losartan (DuP 753, MK-954) and their inhibitory effect on the pressure response to a given bolus of angiotensin I or II. It was found that the maximal inhibitory effect was reached with a dose of 80 mg. The minimal dose necessary for maximal efficacy would therefore be expected to be between 40 and 80 mg. The effect lasted for more than 24 h and was related almost exclusively to the circulating levels of the active metabolite EXP3174. It remains to be demonstrated in hypertensive patients that the same dose relationship holds for the antihypertensive effect, but preliminary data already suggest that this is the case. Am J Hypertens 1992;5:243S-246

Dose-Related Effects of ACE Inhibition in Man: Quinapril in Patients with Moderate Congestive Heart Failure

Early treatment with ACE inhibitors of even moderate heart failure is clinically beneficial, even though haemodynamic measurements cannot adequately quantitate such improvement. Neurohumoral assessment is, however, supposed to be more accurate In 55 patients with moderate heart failure (ejection fraction ≤ 35%), we investigated the dose-dependent effects of ACE inhibition with quinapril taken orally (2.5, 5 or 10 mg b.i.d.) following a placebo-controlled, parallel design protocol over 12 weeks. Plasma components of the renin angiotensin system, catecholamines and ANF were measured together with haemodymmics both at rest and during exercise. Before ACE inhibitor treatment, median PRA, Ang I and II and catecholamines were normal, while ANF was increased All these parameters including ACE activity, rose during exercise. Chronic inhibition of ACE activity was dose-dependent and the maximal fall in Ang If occurred with quinapril 20 mg.day−1. Humoral changes appeared more assessible than haemodymmic alterations even though many of these changes were reasonably correlated. The effects of chronic ACE inhibition on circulating neurohumoral components in patients with moderate heart failure are small and dose-dependent. Since humoral changes are related to haemodynamics they should account for the clinical benefit. Appropriately high doses of ACE inhibitors should be chosen for treatment of heart failur