Effect of intrarenal infusion of angiotensin-(1-7) in the dog.
Angiotensin-(1-7), (Ang-(1-7)), a metabolite of Ang II and /or Ang I, was infused into the renal artery (i.r.a) of anesthetized dogs in order to demonstrate its possible direct renal action. The dose administered, 15 Ig/kg BW/min in isotonic saline (0.072 ml/kg BW/min) throughout the experiment, did not influence the systemic arterial pressure and water and sodium excretion from the contralateral noninfused kidney. Renal blood flow (RBF) was measured by an electromagnetic flowmeter, glomerular filtration rate (GFR) by (exogenous) creatinine clearance. In other groups of animals, either EXP 3174, an AT-1 receptor antagonist alone (30 Ig/kg BW/ min) or together with Ang-(1-7) (15 Ig/kg BW/min), were infused. In the last group, the AT-2 receptor antagonist PD 123319, 10 Ig/kg BW/min, was added to the infusion of Ang-(1-7). A small but significant decrease of RBF from 4.51+/-0.32 to 3.8+/-0.29 ml/g BW/min occurred after Ang-(1-7); this decrease was very similar when PD 123319 was added. However, an increase to 4.98+/-0.34 ml/g BW/min was seen after the addition of EXP 3174 to the i.r.a. infusion of Ang-(1-7); this increase was similar to the increase observed after EXP 3174 alone (5.21+/-0.33; p<0.02 in both cases). A very small but significant increase in GFR was seen after Ang-(1-7) + EXP 3174 or after the AT-1 blocker alone (0.64+/-0.049 and 0.62+/-0.05 vs. 0.6+/-0.05 ml/g BW/min in the Time Control Group, p<0.01 and 0.05, respectively). Water, sodium and urea excretion rates were increased in all groups infused with Ang-(1-7); after the combination of Ang-(1-7) + EXP 3174, all increases were higher than after every substance alone; however, statistical significance (p<0.05) was reached in sodium excretion values only. Potassium excretion rates were increased just in those groups in which EXP 3174 was present in the infusion fluid. In summary, Ang-(1-7) i.r.a. infusion in the dog is followed by increases in water, sodium and urea (but not potassium) excretion rates, highly probably of tubular origin. This effect is not completely blocked by the AT-1 - and not at all by the AT-2 receptor antagonist - thus indirectly suggesting another receptor could play a role. A small decrease in RBF disappears after EXP 3174, thus indicating an AT-1 receptor action.
Heller
J
J
Department of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. jihe@medicon.cz
Kramer
H J
HJ
Malý
J
J
Cervenka
L
L
Horácek
V
V
D000803:Angiotensin I; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019808:Losartan; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011945:Receptors, Angiotensin / Q000378:metabolism; D012077:Renal Artery / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology; D014563:Urodynamics / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D010446:Peptide Fragments; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D014665:Vasodilator Agents; D000804:Angiotensin II; D000803:Angiotensin I; C066026:losartan carboxylic acid; C118790:angiotensin I (1-7); D019808:Losartan