NDT Advance Access originally published online on September 27, 2005
Nephrology Dialysis Transplantation 2005 20(12):2681-2689; doi:10.1093/ndt/gfi136
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Angiotensin II sensitivity of afferent glomerular arterioles in endothelin-1 transgenic mice
1 Johannes-Müller-Institute of Physiology, University Hospital Charité, Humboldt-University of Berlin, Berlin, Germany, 2 Department of Medical Cell Biology, Division of Physiology, University of Uppsala, Uppsala, Sweden, 3 Institute of Pathology, Hospital Braunschweig, Braunschweig, Germany, 4 Center for Cardiovascular Research (CCR)/Department of Pharmacology and Toxicology, University Hospital Charité, Humboldt-University of Berlin, Berlin, Germany, 5 Institute of Experimental and Clinical Pharmacology and Toxicology, University of Luebeck, Luebeck, Germany, 6 Division of Nephrology and Hypertension, Inselspital, University of Berne, Berne, Switzerland
Correspondence and offprint requests to: Andreas Patzak, Johannes-Müller-Institut für Physiologie, Humboldt-Universität zu Berlin, Universitätsklinikum Charité, Tucholskystr. 2, 10117 Berlin. Email: andreas.patzak{at}charite.de
Background. Although endothelin I (ET-1) is a very potent vasoconstrictor, ET-1 transgenic (ET-1 tg) mice are not hypertensive. This might be due to higher bioavailability of nitric oxide (NO) in ET-1 tg, which counteracts the effect of vasoconstrictors. We hypothesized lower angiotensin II (Ang II) sensitivity of afferent arterioles in ET-1 tg.
Methods. Afferent arterioles were manually dissected and microperfused. Changes of the luminal diameter due to application of vasoactive substances were used for assessment of the reactivity of afferent arterioles. We investigated the effect of L-NAME, an unspecific NO synthase inhibitor, on basal tone, and the sensitivity of afferent arterioles to Ang II with and without pre-treatment with L-NAME. The renin-angiotensin-system was characterized by expression analysis of angiotensin-receptors and renin at the mRNA level.
Results. L-NAME reduced afferent arterioles diameters similarly in ET-1 tg and wild-types (WT). Ang II sensitivity determined by calculation of EC50 for Ang II was less in ET-1 tg compared with WT (P<0.05). Ang II reduced luminal diameters to a lesser extent in ET-1 tg compared to WT (P<0.05). After pre-treatment with L-NAME, Ang II sensitivity and maximum constriction of afferent arterioles were similar in ET-1 tg and WT. The expression of renin- and Ang II-receptor-mRNA in the kidney did not differ between either group.
Conclusion. The loss of differences in the maximum constriction and Ang II sensitivity of afferent arterioles between ET-1 tg and WT in the absence of NO suggests pronounced NO effects in afferent arterioles of ET-1 tg. This might contribute to the maintenance of normal renal arteriolar tone in ET-1 tg mice.
Keywords: afferent arteriole; angiotensin II; endothelin; ET-1 transgenic mouse; nitric oxide
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