Angiotensin AT2 receptors directly stimulate renal nitric oxide in Bradykinin B2-receptor-null mice

Peter M. Abadir, Robert M. Carey, Helmy M. Siragy

Research output: Contribution to journalArticlepeer-review

Abstract

Both bradykinin B2 and angiotensin II type 2 (AT2) receptors are known to stimulate renal production of nitric oxide (NO). To evaluate the individual contributions of AT2 and B2 receptors to renal NO production, we monitored renal interstitial, stable NO metabolites and cGMP by a microdialysis technique in conscious, bradykinin B2-null and wild-type mice (n=8 in each group) during low sodium intake alone or with the angiotensin AT1 or AT2 receptor blockers, valsartan (0.5 μg/min) or PD123319 (0.15 μg/min), or both. During normal salt intake, renal interstitial fluid NO and cGMP levels in B 2-null mice were not different from those of wild-type mice. Low sodium intake increased NO and cGMP in wild-type mice but not in B 2-null mice. Valsartan increased NO and cGMP in both wild-type and B2-null mice but to a significantly greater degree in the wild-type than in B2-null mice. PD123319 decreased NO and cGMP in both wild-type and B2-null mice. Combined valsartan and PD123319 decreased NO and cGMP in both wild-type and B2-null mice, but there was no significant difference during combined treatment from their levels after administration of PD123319 alone. Our results indicate that during ingestion of a low-salt diet, production of NO is mediated mainly via the AT 2-B2 receptor cascade. Blockade of the AT1 receptor enhances the production of NO via the AT2 receptor in both wild-type and B2-null mice. We conclude that NO can be produced by 2 alternative pathways: directly through the AT2 receptor or indirectly from AT2 receptor stimulation of bradykinin via the B 2 receptor.

Original languageEnglish (US)
Pages (from-to)600-604
Number of pages5
JournalHypertension
Volume42
Issue number4 I
DOIs
StatePublished - Oct 1 2003
Externally publishedYes

Keywords

  • Angiotensin II
  • Animals, transgenic
  • Cyclic GMP
  • Nitric oxide
  • Receptors, angiotensin II
  • Receptors, bradykinin

ASJC Scopus subject areas

  • Internal Medicine

Fingerprint Dive into the research topics of 'Angiotensin AT<sub>2</sub> receptors directly stimulate renal nitric oxide in Bradykinin B<sub>2</sub>-receptor-null mice'. Together they form a unique fingerprint.

Cite this