Renal-specific actions of angiotensin II receptor antagonism in the anesthetized dog

D. P. Chan, E. K. Sandok, L. L. Aarhus, D. M. Heublein, John C Jr. Burnett

Research output: Contribution to journalArticle

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Abstract

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 μEq/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 μEq/min) response was observed despite a concurrent decrease in plasma aldosterone (10.8 ± 1.5 to 8.1 ± 1.0 ng/dL). In a second group of dogs, a time control study was performed using a vehicle infusion in a similar protocol to the one used in the first group of studies. No significant changes were noted in the cardiovascular and renal hemodynamic and excretory functions listed above during vehicle infusion in a group of time-control animals. The present study demonstrates that, in the anesthetized dog, specific AII receptor antagonism with DuP 753 results in a greater renal, rather than cardiovascular, effect, such that AII antagonism has selective renal vasodilatory actions and promotes diuresis and natriuresis.

Original languageEnglish (US)
Pages (from-to)354-360
Number of pages7
JournalAmerican Journal of Hypertension
Volume5
Issue number6 I
StatePublished - 1992

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Angiotensin Receptors
Dogs
Kidney
Losartan
Hemodynamics
Angiotensin II
Sodium
Vascular Resistance
Natriuresis
Renal Circulation
Angiotensin Receptor Antagonists
Diuresis
Renin-Angiotensin System
Aldosterone
Glomerular Filtration Rate
Lithium
Diuretics
Cardiac Output
Arterial Pressure
Control Groups

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Renal-specific actions of angiotensin II receptor antagonism in the anesthetized dog. / Chan, D. P.; Sandok, E. K.; Aarhus, L. L.; Heublein, D. M.; Burnett, John C Jr.

In: American Journal of Hypertension, Vol. 5, No. 6 I, 1992, p. 354-360.

Research output: Contribution to journalArticle

Chan, DP, Sandok, EK, Aarhus, LL, Heublein, DM & Burnett, JCJ 1992, 'Renal-specific actions of angiotensin II receptor antagonism in the anesthetized dog', American Journal of Hypertension, vol. 5, no. 6 I, pp. 354-360.
Chan, D. P. ; Sandok, E. K. ; Aarhus, L. L. ; Heublein, D. M. ; Burnett, John C Jr. / Renal-specific actions of angiotensin II receptor antagonism in the anesthetized dog. In: American Journal of Hypertension. 1992 ; Vol. 5, No. 6 I. pp. 354-360.
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