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1 Unite 367, Physiologie et Pathologie Experimentale Vasculaire, Institut National de la Sante et de la Recherche Medicale, Universite Paris VI, paris, France
2 Unite de Recherche Associee 1859, Centre National de la Recherche Scientifique, Saclay, France
* To whom correspondence should be addressed. E-mail: marchett{at}ifm.inserm.fr.
Angiotensin II controls the vascular tone of pre- and post-glomerular arterioles, and thereby the glomerular filtration, through binding to either AT1A, AT1B, or AT2 receptors. AT1 receptors, which are coupled to intracellular Ca2+ signaling, have vasoconstricting effects whereas AT2 receptors, whose signaling mechanism is unknown, induce vasodilatation. The angiotensin receptors have been characterized in afferent arterioles, which express the three types of receptors, but not in efferent arterioles. Two subpopulations of juxtamedullary efferent arterioles, muscular ones which terminate as vasa rectae and thin ones which terminate as peritubular capillaries, have been described. They display functional heterogeneity with regard to angiotensin II response. To evaluate whether these differences are associated with differential expression of angiotensin II receptors, we examined the expression pattern of AT1A, AT1B and AT2 receptor mRNAs by RT-PCR in these arterioles, and studied the effect of valsartan, a specific AT1 receptor antagonist. Results indicate that muscular arterioles express AT1A, AT1B and AT2 receptors whereas thin arterioles only express the AT1A and AT2 types, and at a much lower level. Valsartan fully inhibited angiotensin II-induced increases in intracellular calcium in both arteriole types, but with different kinetics. In muscular arterioles, inhibition was mono-exponential whereas it displayed a marked positive cooperativity in thin arterioles. Finally, the apparent affinity for valsartan was higher in muscular than in thin arterioles. In conclusion, this study further documents the differences between muscular and thin efferent arterioles with regard to Ang II signalization in the rat kidney.
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