Increased expression of glomerular AT1 receptors in rats with myocardial infarction.
Rats with congestive heart failure demonstrate striking intrarenal vasoconstriction that contributes to reduced renal excretory function. We previously demonstrated that inhibition of angiotensin action reverses intrarenal vasoconstriction in rats 4-6 wk after coronary artery ligation. In the present study we tested the hypothesis that abnormalities in the expression and regulation of glomerular angiotensin receptors contribute to the intrarenal vasoconstriction. Because glomerular angiotensin type 1 (AT1) receptors normally downregulate in response to high local ANG II concentrations, we anticipated that glomerular AT1-receptor expression would be reduced in rats after myocardial infarction (MI). To our surprise, the density of glomerular AT1 receptors was nearly double (97% increase, P < 0.002) that of controls, indicating an acquired abnormality in angiotensin receptor regulation. This was specific for renal glomeruli, because the density of angiotensin receptors on renal vasculature was decreased in rats after MI compared with normal controls. Glomerular AT1-receptor expression was downregulated by an acute pharmacological infusion of ANG II and upregulated by acute angiotensin-converting enzyme inhibition to a similar extent in MI and control rats. Renal cortical mRNA expression showed an increase in the renin mRNA-to-actin ratio and angiotensinogen-to-actin ratio, indicating stimulation of the intrarenal angiotensin system in rats after MI. The data indicate a specific dysregulation of AT1 receptors in glomeruli but not blood vessels after MI.
Mento
P F
PF
Division of Nephrology and Hypertension, Department of Medicine, North Shore University Hospital, and Department of Medicine, New York University School of Medicine, Manhasset, New York 11030, USA.
Pica
M E
ME
Hilepo
J
J
Chang
J
J
Hirsch
L
L
Wilkes
B M
BM
D000199:Actins / Q000235:genetics; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D007672:Kidney Cortex / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000096:biosynthesis / Q000235:genetics*; D012016:Reference Values; D012079:Renal Circulation / Q000502:physiology*; D012083:Renin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation
D000199:Actins; D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D000804:Angiotensin II; D012083:Renin