Angiotensin-(1-7) stimulates water transport in rat inner medullary collecting duct: evidence for involvement of vasopressin V2 receptors.
The peptide angiotensin-(1-7) [Ang-(1-7)] is known to enhance water transport in rat inner medullary collecting duct (IMCD). The aim of this study was to determine the mechanism of the Ang-(1-7) effect on osmotic water permeability (Pf). Pf was measured in the normal rat IMCD perfused in vitro in presence of agonists [Ang-(1-7), arginine vasopressin (AVP) and Ang-(3-8)], and antagonists of the angiotensin and the vasopressin cascade. Ang-(1-7), but not Ang-(3-8), increased Pf significantly. The effect of Ang-(1-7) on Pf was abolished by its selective antagonist, A-779, added before or after Ang-(1-7). Prostaglandin E2 and the protein kinase A inhibitor H8 also blocked the Ang-(1-7) effect. Blockade of vasopressin V1 receptors by antagonists did not change the Ang-(1-7) effect, but pre-treatment with a V2 antagonist abolished the effect of Ang-(1-7) on Pf. Similarly, pre-treatment with A-779 inhibited AVP's effect on Pf. Forskolin-stimulated Pf was blocked both by A-779 and by the V2 antagonist. Finally, Ang-(1-7) increased cAMP levels in fresh IMCD cell suspensions whilst the forskolin-stimulated cAMP synthesis was decreased by A-779 and the V2 antagonist. These data provide evidence that Ang-(1-7) interacts via its receptor with the AVP V2 system through a mechanism involving adenylate-cyclase activation.
Magaldi
Antonio J
AJ
Laboratório de Pesquisa Básica, LIM 12, Hospital das Clínicas, Faculdade de Medicina, Disciplina de Nefrologia, Universidade de São Paulo, Ave. Dr Arnaldo 455, SP 01246-903 São Paulo, Brazil. biomag@usp.br
Cesar
Katia R
KR
de Araújo
Magali
M
Simões e Silva
Ana C
AC
Santos
Robson A S
RA
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D009995:Osmosis; D010446:Peptide Fragments / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017483:Receptors, Vasopressin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014867:Water / Q000378:metabolism*
C092006:7-Ala-angiotensin (1-7); D065092:Antidiuretic Hormone Receptor Antagonists; D010446:Peptide Fragments; D020033:Protein Isoforms; D017483:Receptors, Vasopressin; D014867:Water; D000804:Angiotensin II; D005576:Colforsin; D000803:Angiotensin I; D000242:Cyclic AMP; C118790:angiotensin I (1-7)