Renal actions of the selective angiotensin AT2 receptor ligands CGP 42112B and PD 123319 in the sodium-depleted rat.
The purpose of this study was to investigate the renal actions of the new selective angiotensin AT2 receptor ligands, CGP 42112B and PD 123319, in comparison to those of the AT1 receptor antagonist losartan, in the sodium-depleted, anesthetized rat. Losartan (1, 3 and 10 mg/kg i.v.) produced a dose-dependent decrease in blood pressure and renal vascular resistance that was statistically significant. Effective renal blood flow tended to increase in response to all doses of losartan while glomerular filtration rate either did not change or decreased, leading to a significant fall in filtration fraction. Losartan did not induce significant changes in urine volume, urinary sodium excretion, urinary potassium excretion or free water formation. The selective AT2 receptor ligand CGP 42112B at infusion rates of 1-100 micrograms/kg per min i.v. had no significant effect on blood pressure or any measured parameter of renal function. However, when infused at 1000 micrograms/kg per min i.v., CGP 42112B did not affect blood pressure, but significantly increased effective renal blood flow, glomerular filtration rate, urinary sodium excretion, urinary potassium excretion and free water formation, while significantly decreasing renal vascular resistance. The selective AT2 receptor ligand PD 123319 at infusion rates between 1 and 100 micrograms/kg per min i.v. also had no significant effect on blood pressure or on any measured parameter of renal function. However, at an infusion rate of 1000 micrograms/kg per min i.v., PD 123319 tended to increase renal vascular resistance, urinary sodium excretion, urinary potassium excretion and free water formation, and to decrease effective renal blood flow, although none of these changes reached a level of statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
Macari
D
D
Cardiovascular Research, Ciba Ltd., Basel, Switzerland.
Bottari
S
S
Whitebread
S
S
De Gasparo
M
M
Levens
N
N
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000097:blood / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004039:Diet, Sodium-Restricted; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007093:Imidazoles / Q000097:blood / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D019808:Losartan; D008297:Male; D009842:Oligopeptides / Q000097:blood / Q000494:pharmacology*; D011188:Potassium / Q000652:urine; D011725:Pyridines / Q000097:blood / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013777:Tetrazoles / Q000097:blood / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D009842:Oligopeptides; D011725:Pyridines; D013777:Tetrazoles; D000804:Angiotensin II; C060894:CGP 42112A; C073402:PD 123319; D012964:Sodium; D019808:Losartan; D011188:Potassium