Renal hemodynamics in rats with myocardial infarction: selective antagonism of angiotensin receptor subtypes.
Rats with congestive heart failure demonstrate striking intrarenal vasoconstriction that contributes to reduced renal excretory function. The importance of specific angiotensin II receptor subtypes (AT1, AT2) for mediating changes in renal hemodynamics was studied in anesthetized rats 1 mo after myocardial infarction (MI) created by coronary artery ligation. AT1 antagonism with losartan alone decreased mean arterial pressure (MAP), total peripheral resistance (TPR), and renal resistance (RR) in control and MI rats to a similar extent without affecting renal blood flow (RBF) or RBF as a percentage of cardiac output (%RBF/CO). In contrast, AT2 antagonism with PD-123319 alone significantly reduced MAP and RR in MI rats without affecting these parameters in control rats. TPR and %RBF/CO were not changed significantly in either group. In contrast, combined AT1- and AT2-receptor inhibition lowered TPR and RR and increased RBF and %RBF/CO, thus the effects of renin or ACE inhibition were mimicked in MI rats. We conclude that angiotensin II acts at both AT1 and AT2 receptor sites in rats with reduced cardiac mass to modulate renal hemodynamics.
Mento
P F
PF
Department of Medicine, North Shore University Hospital, Manhasset, New York 11030, USA.
Maita
M E
ME
Wilkes
B M
BM
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D006439:Hemodynamics; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012079:Renal Circulation; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D013777:Tetrazoles; C073402:PD 123319; D019808:Losartan