Hoe 140 (d‐Arg‐[Hyp3, Thi5, d‐Tic7, Oic8]bradykinin) is a new bradykinin (BK)‐antagonist. It was tested in several in vitro assays and compared with d‐Arg‐[Hyp2, Thi5,8,d‐Phe7]BK. In receptor binding studies in guinea‐pig ileum preparations, Hoe 140 showed an IC50 of 1.07 × 10−9mol l−1 and a KI value of 7.98 × 10−10 mol l−1. In isolated organ preparations Hoe 140 and d‐Arg‐[Hyp2, Thi5,8, d‐Phe7]BK inhibited bradykinin‐induced contractions concentration dependently, with IC50‐values in the guinea‐pig ileum preparation of 1.1 × 10−8 mol l−1 and 3 × 10−5 mol l−1, respectively. pA2 values in this tissue were 8.42 and 6.18, respectively. In the rat uterus preparation the IC50 value was 4.9 × 10−9 mol l−1 for Hoe 140. d‐Arg‐[Hyp2, Thi5,8, d‐Phe7]BK showed an IC50 of 4.0 × 10−6 mol l−1. The IC50 values in the guinea‐pig isolated pulmonary artery were 5.4 × 10−9 mol l−1 and 6.4 × 10−6 mol l−1, respectively. In the rabbit aorta no inhibitory effects on Des‐Arg9‐BK induced contractions were observed. In cultured bovine endothelial cells, Hoe 140 antagonized (IC50 = 10−8 mol l−1) bradykinin‐induced endothelium‐derived relaxing factor (EDRF) release and the bradykinin‐induced increase in cytosolic free calcium (IC50 = 10−9 mol l−1). Hoe 140 (10−7 mol l−1) totally suppressed the bradykinin‐induced (10−8 to 10−4mol l−1) prostacyclin (PGI2) release from cultured endothelial cells of bovine aorta. d‐Arg‐[Hyp2, Thi5,8, d‐Phe7]BK (10−7 mol l−1) showed a weaker antagonism. Taken together these results show that Hoe 140 is a highly potent bradykinin antagonist. It was two to three orders of magnitude more potent than d‐Arg‐[Hyp2, Thi5,8, d‐Phe7]BK.

In conscious dogs, intravenous doses of 0.01 and 0.1 mgkg-1 of Hoe 140 and D-Arg-[Hyp2, Thi5'8, D-Phe7]BK were well tolerated. At doses of 1 mg kg-adverse effects occurred that were attributed to the residual BK agonistic activity of both compounds. 6 Hoe 140 has been shown to be a highly potent and long acting BK antagonist in vivo in different animal species and models. This makes it appropriate to investigate further the physiological and pathophysiological role of BK.

HOE642 is a very selective NHE subtype 1 inhibitor showing cardioprotective and antiarrhythmic effects in ischaemic and reperfused hearts. Further development of well tolerated compounds like HOE642 could lead to a new therapeutic approach in clinical indications related to cardiac ischaemia and reperfusion.

known among most individuals involved in laboratory animal care and use. Most of the time insiders refer to it as the 'Guide'. In the year 2011, ILAR published its eighth edition. This new edition gathered the latest facts, incorporated up-to-date knowledge and reorganized the contents to provide better guidance to laboratory animal care and use programmes.The history of the Guide began in 1946, when Dr Nathan R Brewer and his colleagues in the Chicago area started to improve the care and wellbeing of laboratory animals by exchanging ideas at monthly meetings. The activities of this group led, in 1950, to the foundation of the Animal Care Panel (ACP), which became a growing non-profit organization and was later renamed as American Association for Laboratory Animal Science (AALAS). In 1963, the Animal Facilities Standards Committee of the ACP prepared the first edition of the Guide for the Care and Use of Laboratory Animals. Gradually, the Guide has become the primary reference in many research organizations in the USA, and compliance with it is obligatory for the Public Health Service (PHS)-assured institutions. When the Association for the Assessment and Accreditation for Laboratory Animal Care (AAALAC International) expanded its activities beyond the USA and went international, the Guide became a resource for animal care and use programmes around the world. Today the Guide is one of three primary standards AAALAC uses to evaluate an institution's animal care and use programme. The other two documents are the Guide for the Care and Use of Agricultural Animals in Research and Teaching (Ag Guide), FASS 2010; and the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes, Council of Europe (ETS 123).Over time, the Guide was updated several times culminating in the seventh edition being published in 1996. In the last decade, laboratory animal science advanced so significantly that another update was considered necessary to promote the best animal care and use practices. In 2006, a committee was appointed by the National Research Council in the USA, and started the process of updating the Guide. This process was accompanied by extensive public hearings and solicited comments from a wide range of scientific communities and the public. Fifteen years after its seventh edition, the new eighth edition of the Guide was finally completed and published.

1 The benzoylguanidine derivative Hoe 694 ((3-methylsulphonyl-4-piperidino-benzoyl) guanidine methanesulphonate) was characterized as an inhibitor of Na+/H+ exchange in rabbit erythrocytes, rat platelets and bovine endothelial cells. The potency of the compound was slightly lower or comparable to ethylisopropyl amiloride (EIPA). 2 To investigate a possible cardioprotective role of the Na+/H+ exchange inhibitor Hoe 694, rat isolated working hearts were subjected to ischaemia and reperfusion. In these experiments all untreated hearts suffered ventricular fibrillation on reperfusion. Addition of 1O-7M Hoe 694 to the perfusate almost abolished reperfusion arrhythmias in the rat isolated working hearts. 3 Hoe 694 reduced the release of lactate dehydrogenase (LDH) and creatine kinase (CK), which are indicators of cellular damage during ischaemia, into the venous effluent of the hearts by 60% and 54%, respectively. 4 The tissue content of glycogen at the end of the experiments was increased by 60% and the high energy phosphates ATP and creatine phosphate were increased by 240% and 270% respectively in the treated hearts as compared to control hearts. 5 Antiischaemic effects of the Na+/H+ exchange inhibitor, Hoe 694, were investigated in a second experiment in anaesthetized rats undergoing coronary artery ligation. In these animals, pretreatment with Hoe 694 caused a dose-dependent reduction of ventricular premature beats and ventricular tachycardia as well as a complete suppression of ventricular fibrillation down to doses of 0.1 mg kg-', i.v. Blood pressure and heart rate remained unchanged. 6 We conclude that the new Na+/H+ exchange inhibitor, Hoe 694, shows cardioprotective and antiarrhythmic effects in ischaemia and reperfusion in rat isolated hearts and in anaesthetized rats. In view of the role which Na+/H+ exchange seems to play in the pathophysiology of cardiac ischaemia these effects could probably be attributed to Na+/H+ exchange inhibition.