Renal-specific actions of angiotensin II receptor antagonism in the anesthetized dog.
The role of angiotensin II (AII) in the regulation of systemic hemodynamic and renal function and sodium excretion, although important in states characterized by the activation of the renin-angiotensin system, remains unclear under basal conditions. The current studies were designed to define the role of AII in the basal regulation of cardiovascular and renal function using a specific AII receptor antagonist, DuP 753, in the normal anesthetized dog. No changes in mean arterial pressure, cardiac output, or systemic vascular resistance were observed during the infusion of DuP 753. In contrast, a significant increase in glomerular filtration rate (19.7 +/- 0.9 to 26.1 +/- 2.0 mL/min) and renal blood flow (151 +/- 20 to 188 +/- 26 mL/min), with a decrease in renal vascular resistance (0.85 +/- 0.10 to 0.66 +/- 0.06 mm Hg/mL/min) was observed. Associated with the renal hemodynamic changes, a diuretic (0.16 +/- 0.05 to 0.57 +/- 0.21 mL/min) and natriuretic (31.2 +/- 7.0 to 100.5 +/- 22.2 microEq/min) response was also demonstrated. Renal hemodynamic changes were also associated with a decrease in tubular sodium reabsorption characterized by an increase in the fractional excretion of sodium (1.10 +/- 0.3 to 2.61 +/- 0.62%), with an associated decrease in whole-kidney proximal tubular reabsorption indicated by an increase in fractional excretion of lithium (31.2 +/- 2.2 to 40.8 +/- 3.9%). In addition, a kaliuretic (17.9 +/- 2.1 to 27.1 +/- 2.4 microEq/min) response was observed despite a concurrent decrease in plasma aldosterone (10.8 +/- 1.5 to 8.1 +/- 1.0 ng/dL).(ABSTRACT TRUNCATED AT 250 WORDS)
Chan
D P
DP
Department of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, MN 55905.
Sandok
E K
EK
Aarhus
L L
LL
Heublein
D M
DM
Burnett
J C
JC
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects*; D019808:Losartan; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009994:Osmolar Concentration; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D014677:Pharmaceutical Vehicles; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan