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

• Published in: Brain research Vol. 873; no. 1; pp. 75 - 82
• Main Authors: Feterik, Kristian, Smith, Leslie, Katusic, Zvonimir S
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 04-08-2000; Amsterdam Elsevier; New York, NY
• Subjects: Angiotensin I - pharmacology; Angiotensin receptor; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Biological and medical sciences; Bradykinin; Bradykinin Receptor Antagonists; Cerebral Arteries - drug effects; Cerebral Arteries - metabolism; Cerebral Arteries - physiology; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cerebral vessel; Converting enzyme inhibitor; Cyclic GMP - biosynthesis; Cyclooxygenase Inhibitors - pharmacology; Dogs; Endothelium, Vascular - physiology; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Nitric oxide; Peptide Fragments - pharmacology; Vertebrates: nervous system and sense organs; Other systems of the CNS; cGMP, cyclic guanosine 3′5′-monophosphate; Converting enzyme inhibitor; ACE, angiotensin-converting enzyme; l-NAME, N-ω-nitro- l-arginine methyl ester; UTP, uridine 5′-triphosphate; Angiotensin receptor; ODQ, 1H-[1, 2, 4]oxadiazolo[43- a]quinozalin-1-one; HOE 140, [ d-Arg 0, Hyp 3, Thi 5, d-Tic 7, Oic 8]-bradykinin; Cerebral vessel; Sarthran, [Sar 1, Thr 8]-angiotensin II; Bradykinin; Nitric oxide; Dogs; Saralasin, [Sar 1, Val 5, Ala 8]-angiotensin II; Fissipedia; Carnivora; Middle cerebral artery; Vasodilation; Endothelium; Renin angiotensin system; Vasomotricity; Vertebrata; Mammalia; Angiotensin; Dog; Biological receptor
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(00)02482-3

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, 3×10
−6 to 10
−5 mol/l), angiotensin-(1–7) (10
−9 to 3×10
−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, 3×10
−4 mol/l), and selective soluble guanylate cyclase inhibitor, 1 H-[1,2,4]oxadiazolo[4,3-
a]quinozalin-1-one (ODQ, 3×10
−6 mol/l), abolished angiotensin-(1–7)-induced relaxations. Angiotensin receptor antagonists, losartan (10
−5 mol/l), PD 123 319 (10
−5 mol/l), [Sar
1,Thr
8]-angiotensin II (10
−5 mol/l) [Sar
1,Val
5,Ala
8]-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 B
2 receptor antagonist, [
d-Arg
0,Hyp
3,Thi
5,
d-Tic
7,Oic
8]-bradykinin (HOE 140, 5×10
−8 mol/l) significantly reduced the effect of angiotensin-(1–7), while bradykinin B
1 receptor antagonist, des-Arg
9, [Leu
8]-bradykinin (6×10
−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.