Angiotensin receptor subtypes in thin and muscular juxtamedullary efferent arterioles of rat kidney.
ANG II controls the vascular tone of pre- and postglomerular arterioles, and thereby 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 the ANG II response. To evaluate whether these differences are associated with differential expression of ANG 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 ANG II-induced increases in intracellular Ca2+ in both arteriolar types, but with different kinetics. In muscular arterioles, inhibition was monoexponential, 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.
Institut National de la Santé et de la Recherche Médicale Unité 367, Physiologie et Pathologie Expérimentale Vasculaires, Université Paris VI, Paris, France.
Claudia M B
CM
Helou
Martine
M
Imbert-Teboul
Alain
A
Doucet
Rabary
R
Rajerison
Catherine
C
Chollet
François
F
Alhenc-Gelas
Jeannine
J
Marchetti
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D005786:Gene Expression Regulation; D007606:Juxtaglomerular Apparatus / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D014633:Valine; D002118:Calcium