A-779 TFA

Sprague Dawley (female, 9 weeks old)^[1]

24 μg/kg/h

i.v.; continuous infusion; 8 days

Increased urine volume by 126%.
Tended to decrease urinary osmolality.
Did not alter chow consumption and water intake relative to vehicle controls.

Sprague Dawley (female, originally 9 weeks old virgin, pregnant)^[1]

24 μg/kg/h

i.v.; continuous infusion; 8 days pre-pregnancy through gestational day 19

Decreased water consumption by 83% relative to vehicle controls in mid-pregnancy (gestational day 15).
Decreased chow consumption by 83%, decreased water consumption by 80%, and reduced urine volume by 76% relative to vehicle controls in late pregnancy (gestational day 19).
Tended to increase urinary osmolality in late pregnancy.
Had no significant effect on fluid/food intake-output balance, urinary sodium or potassium concentrations, maternal body weight, or fetal characteristics (body weight, length, number).

Wistar (male, 230-320 g)^[3]

80 ng/min

i.v.; continuous infusion

Produced a significant shift of the intravenous bradykinin dose-response curve, requiring approximately two-fold higher bradykinin doses to achieve the same hypotensive effect observed with captopril alone.
Significantly attenuated the captopril-induced potentiation of intra-arterial bradykinin's hypotensive effect.
Did not significantly alter bradykinin's hypotensive effect or baseline MAP when infused alone (without captopril).
Did not modify the pressor effect of angiotensin II.
Did not change captopril's inhibitory effect on angiotensin I's pressor response.
Did not alter the captopril-induced decrease in baseline MAP.

Dahl salt-sensitive (male, 4-5 weeks of age, high 8.0% NaCl salt diet for 2 weeks or low 0.3% NaCl salt diet)^[4]

48 µg/kg (in vivo); 100 pmol (ex vivo tissue incubation)

i.v.; single dose (in vivo); incubated with isolated aortic rings (ex vivo)

Blocked the maximal MAP reduction of -14 mm Hg induced by Ang-(1-7) in high salt diet rats, resulting in a significantly attenuated blood pressure decrease.
Prevented the Ang-(1-7)-induced increase in plasma 6-keto-PGF₁α levels, maintaining levels near basal values.
Prevented the Ang-(1-7)-induced decrease in plasma TXB₂ levels, maintaining levels near basal values.
Prevented the Ang-(1-7)-induced increase in plasma nitric oxide levels, maintaining levels near basal values.
Prevented the Ang-(1-7)-induced increase in aortic ring 6-keto-PGF₁α levels (from 31 to 49 pg/mL/mg ring wt, maintained at 36 pg/mL/mg ring wt) and PGE₂ levels (from basal 22 to Ang-(1-7)-induced 33 pg/mL/mg ring wt, maintained at 21 pg/mL/mg ring wt) in high salt diet rats.
Attenuated the Ang-(1-7)-induced decrease in aortic ring TXB₂ levels (from basal 44 to Ang-(1-7)-induced 23 pg/mL/mg ring wt, increased to 37 pg/mL/mg ring wt) in high salt diet rats.
Prevented the Ang-(1-7)-induced increase in nitric oxide levels in aortic rings from both high and low salt diet rats.
Totally abolished the Ang-(1-7)-induced 52% increase in aortic ring cGMP levels (from basal 102 to Ang-(1-7)-induced 212 fmol/mg protein, maintained at 67 fmol/mg protein) in high salt diet rats.
Had no significant effect on MAP, plasma 6-keto-PGF₁α, TXB₂, nitric oxide, aortic ring 6-keto-PGF₁α, PGE₂, TXB₂, nitric oxide, or cGMP levels compared to basal values in either diet group.