Biomedical subjects

Kerstin Steioff

Publications and source records attributed to Kerstin Steioff.

4 recordsLinked to original sources

PubMed2006

Transcutaneous vascular ultrasound in hypercholesterolaemic rabbits: a new method to evaluate endothelial function.

Measurement of endothelial function in patients with atherosclerosis and lipid disorders is an important tool for the risk evaluation of a cardiovascular event, such as acute myocardial infarction and stroke. The feasibility of measuring endothelial function non-invasively in animal models has been limited so far. Therefore, we compared the assessment of endothelial function by in vivo transcutaneous vascular ultrasound (TVU) with the classical method of ex vivo organ bath, using the carotid artery of hypercholesterolaemic and normocholesterolaemic rabbits. The assessments of endothelial function by both techniques were performed on the same segments of the carotid artery. Vascular ultrasound detected impaired endothelium-dependent vasorelaxation induced by acetylcholine in the common carotid artery of hypercholesterolaemic rabbits. These results strongly correlated with measurements of endothelial function of isolated carotid artery rings. Furthermore, atherogenic diet caused significant fatty streak formation in the aorta, as well as significant increase of C-reactive protein and cholesterol levels. Endothelial function, an early marker of cardiovascular risk, could be non-invasively assessed and graded by TVU measurements. It correlated highly with vasoreactivity of isolated vessels in an organ bath (r(2)=0.68). We conclude that vascular ultrasound in hypercholesterolaemic rabbits is a valid method for evaluating endothelial function associated with atherosclerosis.

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PubMed2005

Long term Rho-kinase inhibition ameliorates endothelial dysfunction in LDL-Receptor deficient mice.

Chronic inhibition of Rho-kinase has been recently implicated in retardation of atherogenesis induced by high-fat diet in low-density lipoprotein receptor deficient (LDLR-/-) mice. However, it remains to be examined whether long-term Rho-kinase inhibition will reduce vascular dysfunction in this model. LDLR-/- mice on a high-fat diet were treated either with saline (LDLR-/-) or with the Rho-kinase inhibitor Fasudil (HA1077, 5-Isoquinolinesulfonyl homopiperazine, 100 mg/kg/day by gavage, LDLR-/- +Fasudil) for 10 weeks. Fasudil-treatment normalized endothelial function (measured by means of endothelium-dependent vasorelaxation) in LDLR-/- +Fasudil, to the level of controls (C57BL/6J). No tolerance toward Rho-kinase inhibition has been detected in Fasudil-treated animals. We conclude that long-term Rho-kinase inhibition normalizes endothelial function without development of tolerance.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2004

Inhibition of Rho-kinase stimulates nitric oxide-independent vasorelaxation.

Vasoconstrictor factors, like urotensin, angiotensin and catecholamines, activate Rho-dependent serine-threonine kinase (Rho-kinase) and inhibition of this pathway represents a novel therapy for cardiovascular diseases with hypertensive syndrome. The disbalance of relaxing endothelial nitric oxide (NO)-producing and vasoconstrictive pathways can be especially important in diseases where hypertension is accompanied by endothelial dysfunction that compromises NO generation. However, a recent study reported that the efficacy of the Rho-kinase inhibitor (R)-(+)-trans-N-(4-Pyridyl)-4-(1-aminoethyl)cyclohexanecarboxamide (Y27632) is dramatically attenuated upon removal of endothelium or inhibition of endothelial NO synthase (eNOS). This raises the question whether Rho-kinase inhibition could be an effective treatment in case of hypertension associated with endothelial dysfunction. The purpose of the present study was to determine whether the vasorelaxing effect of Rho-kinase inhibition is mediated through eNOS-dependent mechanisms. We show here that in the models of genetically reduced endothelial NO production (eNOS-/- mice and spontaneous hypertensive rats (SHR)) or in models of pharmacologically reduced endogenous NO production (N(omega)-nitro-L-arginine methyl ester (LNAME) treatment), Rho-kinase inhibition induced a strong vasodilation and reduction of blood pressure indicating independence of Rho-kinase pathway from eNOS. An additional important finding of our study is that Rho-kinase inhibitors induce a strong vasorelaxation and blood pressure reduction upon intravenous injection not only in hypertensive but in normotensive animals, as well. Inhibition of Rho-kinase represents a promising possibility to treat hypertension that is accompanied by endothelial dysfunction.

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PubMed2004

Chronic vasopeptidase inhibition normalizes diabetic endothelial dysfunction.

Type 2 diabetes mellitus is a major cause of vascular morbidity but animal models for this disease have not been adequately characterized. We demonstrate that endothelial dysfunction is present in the Zucker diabetic fatty (ZDF) rat. Vasopeptidase inhibition with AVE7688 (7-[[(2S)-2-(acetylthio)-1-oxo-3-methylpropyl]amino]-1,2,3,4,6,7,8,12b-octahydro-6-oxo-(4S,7S,12bR)-pyrido[2,1-a][2]benzazepine-4-carboxic acid), 45 mg/kg/day in chow for 6 weeks, normalized acetylcholine mediated relaxation of mesenteric artery rings. Thus, chronic vasopeptidase inhibition may prevent vascular complications related to type 2 diabetes mellitus.

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