title: Intrarenal infusion of angiotensin-(1-7) modulates renal functional responses to exogenous angiotensin II in the rat.
abstract: In the present study we investigated the possible role of angiotensin-(1-7) [Ang-(1-7)] in modulating renal functional responses to intrarenal (i.e.) infusion of angiotensin II (ANG II) in normotensive anesthetized rats. ANG II (6 ng/min, n = 14) decreased glomerular filtration rate (GFR), renal plasma flow (RPF), absolute and fractional sodium excretion by -24 +/- 5, -25 +/- 6, -44 +/- 6 and -28 +/- 7%, respectively (p < 0.05). i.r. infusion of Ang-(1-7) (50 ng/min, n = 13) did not significantly alter GFR (+6 +/- 4%) but reduced RPF by -19 +/- 7% (p < 0.05). Ang-(1-7) increased absolute and fractional sodium excretion by +36 +/- 6 and +37 +/- 8%, respectively (p < 0.05). Infusion of Ang-(1-7) did not prevent the decreases in GFR and RPF but completely blunted the decreases in absolute (-2 +/- 2%) and fractional sodium excretion (-4 +/- 4%) induced by ANG II (n = 11). Blockade of the Ang-(1-7) receptor by [7-D-Ala]-Ang-(1-7) (5 microg/min, n = 11) significantly decreased GFR, RPF, absolute and fractional sodium excretion by -28 +/- 7, -20 +/- 5, -32 +/- 7 and -24 +/- 4%, respectively (p < 0.05), suggesting that the action of endogenous ANG II is unopposed by compensatory effect of endogenous Ang-(1-7). i.r. infusion of Ang-(1-7) (n = 10) did not alter the effect of Ang-(1-7) receptor blockade on RPF (-21 +/- 6%) but blunted its effects on GFR (+4 +/- 3%) and absolute (+7 +/- 5%) and fractional (+6 +/- 4%) urinary sodium excretion probably by displacing the receptor blocker. While exogenous ANG II during blockade of the Ang-(1-7) receptor and the AT(2) receptor (by PD 123319; 1 microg/min i.r., n = 9) resulted in the same decreases in absolute and fractional sodium excretion (-39 +/- 8 and -38 +/- 6%, respectively, p < 0.05) as did ANG II in the absence of Ang-(1-7) receptor blockade. These results suggest that in normotensive rats high i.r. Ang-(1-7) concentration attenuates the tubular, i.e. sodium reabsorptive effect, but not the vascular effect of exogenous i.r. ANG II. Results obtained during blockade of Ang-(1-7) and of AT(2) receptors imply that AT(2) receptors play a role in tubular sodium reabsorption in the presence of high ANG II concentration.
authors.affiliation: Transplant Center, Department of Nephrology, Institute for Clinical and Experimental Medicine, 1858/9 Videnská, 140 00 Prague 4, Czech Republic.
authors.forename: Marcela
authors.initials: M
authors.lastname: Bürgelová
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Kramer
authors.forename: Vladimir
authors.initials: V
authors.lastname: Teplan
authors.forename: Gabriela
authors.initials: G
authors.lastname: Velicková
authors.forename: Stefan
authors.initials: S
authors.lastname: Vítko
authors.forename: Jirí
authors.initials: J
authors.lastname: Heller
authors.forename: Jan
authors.initials: J
authors.lastname: Malý
authors.forename: Ludĕk
authors.initials: L
authors.lastname: Cervenka
mesh_terms: D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044139:Receptor, Angiotensin, Type 2; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D014563:Urodynamics / Q000187:drug effects
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319; D000803:Angiotensin I; D012964:Sodium; C118790:angiotensin I (1-7)