Developmental regulation of ACE gene expression by endogenous kinins and angiotensin II.
Angiotensin converting enzyme (ACE, i.e., kininase II), a key regulator of kinins and angiotensin II (ANG II) generation, is developmentally regulated and its expression is induced at a specific time point (day 15) of postnatal kidney development. The present study tested the hypothesis that endogenous kinins and ANG II regulate the developmental expression of the renal ACE gene. In the first protocol, newborn rats received the kallikrein inhibitor, aprotinin (100,000 KIU.kg-1.day-1 sc), or the kinin B2 receptor antagonist, HOE-140 (600 micrograms.kg-1.day-1 sc), or 0.9% saline, from birth until postnatal days 5, 15, or 20. Aprotinin prevented the postnatal rise in renal kallikrein activity without affecting blood pressure in either developing or adult rats. Chronic kallikrein blockade significantly attenuated the postnatal induction of both serum ACE activity (-11% vs. controls) and kidney ACE activity and mRNA (-50% vs. controls). In addition, aprotinin attenuated the postnatal rise of ACE activity in the developing lungs. Kidney renin mRNA and ANG II contents were not altered by aprotinin. HOE-140 also attenuated the postnatal rise in kidney ACE mRNA (-25%) and activity (-40%) without affecting blood pressure. Infusion of aprotinin or HOE-140 via osmotic minipumps for 7 days in adult rats was not associated with any changes in renal or pulmonary ACE.(ABSTRACT TRUNCATED AT 250 WORDS)
Yosipiv
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Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
el-Dahr
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D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D005786:Gene Expression Regulation; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007704:Kininogens / Q000378:metabolism; D007705:Kinins / Q000502:physiology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D007704:Kininogens; D007705:Kinins; D012333:RNA, Messenger; D000804:Angiotensin II; C065679:icatibant; D007611:Aprotinin; D007703:Peptidyl-Dipeptidase A; D007610:Kallikreins; D012083:Renin; D001920:Bradykinin