Angiotensin II receptor expression in the conduction system and arterial duct of neonatal and adult rat hearts.
Paralleling the classic circulating system, recent evidence has demonstrated the presence of a cardiac renin-angiotensin system, as well as the synthesis of angiotensin II in the heart. Two receptors for angiotensin II have been identified and classified as AT1 and AT2. The proportions of these receptor subtypes vary with the tissues, species and stage of development. From the results of other studies, it might be generalized that the expression of angiotensin II receptors and the proportion of AT2 receptor subtype are much higher in fetal and neonatal tissues than in the same tissues from an adult. The aim of this study was to specifically evaluate the AT1/AT2 ratio in the neonatal and adult conduction systems of rat hearts by means of quantitative autoradiogrphy. In the neonatal hearts, angiotensin II binding sites were highly concentrated in the vasculature, arterial duct, and conduction system, whereas their concentrations were barely detectable in the myocardium. Incubation with selective angiotensin II receptor ligands (losartan and CGP 42112) revealed that AT2 was the major subtype in vasculature (86 +/- 3%) and conduction system (73 +/- 4%). In the adult conduction system, the total expression of angiotensin II receptors was greatly reduced meanwhile the AT1 receptors represented the major proportion of the binding sites (80 +/- 3%). Our results demonstrated that the pattern of angiotensin II receptor expression in the conduction system of the rat heart is developmentally regulated. We suggest, as others have already, that the renin-angiotensin system plays a role during the early stage of cardiac development.
Bastien
N R
NR
Department of Pharmacology, Université de Montréal, Québec, Canada.
Ciuffo
G M
GM
Saavedra
J M
JM
Lambert
C
C
D000804:Angiotensin II / Q000737:chemistry* / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D001283:Atrioventricular Node / Q000378:metabolism* / Q000648:ultrastructure*; D001345:Autoradiography; D001665:Binding Sites; D001713:Biphenyl Compounds / Q000032:analysis / Q000378:metabolism; D005260:Female; D007093:Imidazoles / Q000032:analysis / Q000378:metabolism; D007457:Iodine Radioisotopes; D019808:Losartan; D008297:Male; D009842:Oligopeptides / Q000032:analysis / Q000378:metabolism; D011247:Pregnancy; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism* / Q000648:ultrastructure; D013777:Tetrazoles / Q000032:analysis / Q000378:metabolism
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D007457:Iodine Radioisotopes; D009842:Oligopeptides; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C060894:CGP 42112A; D019808:Losartan