Changes in arterial function in a mouse model of human familial hypercholesterolaemia.

AIM: Atherosclerosis is the most common cause of cardiovascular disease. The ApoB mouse is a model for human familial hypercholesterolaemia and has a lipoprotein profile similar to that of humans with atherosclerosis. Therefore, it is a suitable model to investigate the changes in vasoreactivity during atherogenesis. This study investigates contractile and dilatative properties of arteries in this model in relation to age. METHODS: Male ApoB mice and B6, wild-type (WT), mice were examined at age four or 18 months. Isometric measurements of 2-mm ring preparations of the aorta thoracica were performed using a wire myograph. Histological and biochemical methods served to determine atherosclerosis, lipid status and endothelial markers respectively. RESULTS: Morphometric analysis showed that all old ApoB mice had severe atherosclerosis in the aorta. Atherosclerotic alteration of the aorta of the ApoB mice coincided with a diminished vasodilatation to acetylcholine. The phenylephrine response was significantly attenuated already to the same degree in the non-atherosclerotic aorta of the young ApoB mice as in the atherosclerotic aorta of the older ApoB mice. Serum parameters showed a rise in total cholesterol and triglycerides in the ApoB strain compared to WT mice. Soluble intercellular adhesion molecule (sICAM)-1 and soluble vascular adhesion molecule (sVCAM)-1 were increased in old compared to young ApoB mice. CONCLUSION: The study shows that reduced acetylcholine-induced dilatation is related to the presence of atherosclerosis in old ApoB mice. Remarkably, the impaired vessel reactivity to phenylephrine already in young ApoB mice indicates early changes in vascular function in this model.

Renal outcome in equipotent antihypertensive treatment with telmisartan, ramipril and in combination in SHR-SP rats.

BACKGROUND: The ONTARGET trial revealed an association of ACEI/ARB combination treatment (telmisartan and ramipril) with adverse renal outcome versus respective monotherapy; preclinical evidence regarding renal outcome in ACEI/ARB combination treatment is scarce. METHODS: Spontaneously hypertensive stroke prone rats (SHR-SP) rats on a salt-rich diet were randomly allocated to 4 groups: SHR (untreated, n = 24), SHR + telmisartan (SHR-T, 2.39 +/- 0.69 mg/kg bw; n = 27), SHR + ramipril (SHR-R, 6.28 +/- 3.48 mg/kg bw; n = 27) and combination treatment (SHR-TR, 0.51 +/- 0.14 mg/kg bw; same dose for telmisartan and ramipril; n = 26). Study duration was 12 weeks, blood pressure was assessed weekly and doses were adjusted to maintain equal blood pressure. Finally, blood and urine samples were obtained and kidneys were harvested for histological studies. RESULTS: Blood pressure in untreated rats rose to a maximum of 239 mmHg, whereas in all treatment groups it remained stable between 140 and 150 mmHg. Mortality was 50% in the untreated group, whereas all treatment groups survived completely. Renal function--as indicated by plasma urea and cystatin c--was significantly worse in SHR-TR animals compared to all other groups. With plasma creatinine a similar trend was observed. All treatment options significantly decreased albuminuria. Renal glomerulosclerosis was decreased by monotherapy, whereas combination therapy failed to have a significant effect. Interstitial fibrosis was decreased to a similar extent by all treatment options. CONCLUSIONS: ACEI/ARB combination treatment failed to render significant additional benefits on renal outcome in hypertensive rats when compared to monotherapy. Instead our data indicate that dual RAAS blockade might have an adverse effect on kidney function and histology when compared to monotherapy in salt-loaded SHR-SP.

[Uncommon mycobacterial infections in domestic and zoo animals: four cases with special emphasis on pathology]. / Ungewöhnliche Mykobakterien-Infektionen bei Haus- und Zootieren: eine Kasuistik unter besonderer Berücksichtigung der Pathologie.

Infections caused by classical tubercle bacilli are rare during the last years. Nevertheless, diseases caused by other mycobacteria have to be considered clinically and in diagnostic pathology especially in cases of immunosuppression and due to their potential zoonosis risk. An infection by mycobacteria was diagnosed in four animals (Mayotte Maki, Blue-headed Parrot, Patagonian sealion, Beagle) necropsied between 1995 and 2002 in the Institute of Veterinary-Pathology of the University of Leipzig. The Maki, the blue-headed parrot and the dog showed a disseminated character of the disease caused by Mycobacterium genavense (monkey and bird) resp. Mycobacterium avium (dog), while an open chronical tuberculosis of the lungs due to a pathogenic member of Mycobacterium tuberculosis complex was observed in the seal. All these bacteria are potential causes of zoonoses. So, if granulomatous or disseminated histiocytic alterations are detected in diagnostic pathology, mycobacterial infections should always be included in differential diagnoses and require careful aetiological investigations by histopathological and bacteriological methods.