title: Effect of intratubular application of angiotensin 1-7 on nephron function.
abstract: Cleavage of the C-terminal tripeptide of angiotensin I (Ang I) by neutral endopeptidase 24.11 releases angiotensin 1-7 (Ang 1-7). Because Ang I and neutral endopeptidase 24.11 are present in proximal tubular fluid and brush border, respectively, Ang 1-7 could be released into proximal tubular fluid to affect nephron function. Therefore, we studied the effect of intratubular Ang 1-7 (10(-12) to 10(-8) M) on nephron function employing in vivo renal micropuncture in inactin-anesthetized Munich-Wistar-Frömter rats. We observed that: (i) Intratubular application of Ang 1-7 for 3, 15, or 30 min did not affect reabsorption in the microperfused proximal convoluted tubule determined as net fluid reabsorption. (ii) During perfusion of Henle's loop for 15 min with artificial tubular fluid (time control), we observed a decline in fluid, potassium and sodium reabsorption by 20, 18 and 5%, respectively. A similar decline in reabsorption was seen with intratubular application of Ang 1-7 in a concentration of 10(-12) or 10(-10) M. In contrast, intratubular application of Ang 1-7 in a concentration of 10(-8) M increased fluid, potassium and sodium reabsorption in that nephron segment by 11, 9 and 3%, respectively. The latter response was completely abolished by AT1 angiotensin II receptor antagonist losartan (10[-6] M). (iii) Intratubular application of Ang 1-7 did not affect net sodium, potassium, or fluid reabsorption in the distal tubule. (iv) TGF response assessed by measuring proximal tubular stop-flow pressure or single nephron filtration rate during orthograde open-loop perfusion of Henle's loop was not significantly altered by intratubular application of Ang 1-7. These findings show that intratubular application of Ang 1-7 in concentrations which possibly cover the physiological range does not significantly alter (i) tubular reabsorption in proximal convoluted or distal tubule, or (ii) TGF response. Intratubular Ang 1-7 at a concentration of 10(-8) M appears to increase reabsorption in Henle's loop by an AT1 angiotensin II receptor-mediated mechanism, the physiological relevance of which remains to be established.
authors.affiliation: Department of Pharmacology, University of Tübingen, Germany. volker.vallon@uni-tuebingen.de
authors.forename: V
authors.initials: V
authors.lastname: Vallon
authors.forename: K
authors.initials: K
authors.lastname: Richter
authors.forename: N
authors.initials: N
authors.lastname: Heyne
authors.forename: H
authors.initials: H
authors.lastname: Osswald
mesh_terms: D000042:Absorption; D000803:Angiotensin I; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D005246:Feedback; D007263:Infusions, Parenteral; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009399:Nephrons / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)