Angiotensin-(1-7) causes endothelium-dependent relaxation in canine middle cerebral artery

Kristian Feterik, Leslie Smith, Zvonimir S. Katusic

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62 Scopus citations


The heptapeptide, angiotensin-(1-7), is an active member of the renin-angiotensin system. The present study was designed to characterize the role of endothelium in relaxations of large cerebral arteries to angiotensin-(1-7). Rings of canine middle cerebral arteries were suspended in organ chambers for isometric force recording. The levels of cyclic guanosine 3',5'-monophosphate (cGMP) were assessed by radioimmunoassay. During contraction to uridine 5'-triphosphate (UTP, 3x10-6 to 10-5 mol/l), angiotensin-(1-7) (10-9 to 3x10-5 mol/l) caused concentration-dependent relaxations in arteries with endothelium, but not in endothelium-denuded vessels. Angiotensin-(1-7) significantly increased formation of cGMP. Nitric oxide synthase inhibitor, N-ω-nitro-L-arginine methyl ester (L-NAME, 3x10-4 mol/l), and selective soluble guanylate cyclase inhibitor, 1 H-(1,2,4)oxadiazolo(4,3-a)quinozalin-1-one (ODQ, 3x10-6 mol/l), abolished angiotensin-(1-7)-induced relaxations. Angiotensin receptor antagonists, losartan (10-5 mol/l), PD 123 319 (10-5 mol/l), (Sar1, Thr8)-angiotensin II (10-5 mol/l) (Sar1, Val5, Ala8)-angiotensin II (10-5 mol/l) or (7-D-Ala)-angiotensin 1-7 (10-6 mol/l) did not affect these relaxations. However, angiotensin-converting enzyme inhibitor, captopril (10-5 mol/l) augmented relaxations to angiotensin-(1-7). Finally, bradykinin B2 receptor antagonist, (D-Arg0, Hyp3, Thi5, D-Tic7, Oic8)-bradykinin (HOE 140, 5x10-8 mol/l) significantly reduced the effect of angiotensin-(1-7), while bradykinin B1 receptor antagonist, des-Arg9, (Leu8)-bradykinin (6x10-9 mol/l) did not influence the vascular response to the heptapeptide. These findings indicate that (1) angiotensin-(1-7) produces relaxation of canine middle cerebral arteries by the release of nitric oxide from endothelial cells, (2) angiotensin receptors do not mediate endothelium-dependent relaxations to the heptapeptide, and (3) this effect appears to be dependent on activation of local production of kinins. Our studies support the concept that angiotensin-(1-7), as a natural vasodilator hormone, may counterbalance the hemodynamic actions of angiotensin II.

Original languageEnglish (US)
Pages (from-to)75-82
Number of pages8
JournalBrain Research
Issue number1
StatePublished - Aug 4 2000


  • Angiotensin receptor
  • Bradykinin
  • Cerebral vessel
  • Converting enzyme inhibitor
  • Dogs
  • Nitric oxide

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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