TY - JOUR
T1 - Angiotensin-(1-7) causes endothelium-dependent relaxation in canine middle cerebral artery
AU - Feterik, Kristian
AU - Smith, Leslie
AU - Katusic, Zvonimir S.
N1 - Funding Information:
This work was supported in part by National Heart, Lung, and Blood Institute grant HL-53524 and National Institute of Neurological Disorders and Stroke grant NS-37491, funds from the Bruce and Ruth Rappaport Program in Vascular Biology, and the Mayo Foundation. The authors would like to thank Ms. Janet Beckman for preparing the manuscript and Dr. Gautam Khurana for valuable advice.
PY - 2000/8/4
Y1 - 2000/8/4
N2 - 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.
AB - 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.
KW - Angiotensin receptor
KW - Bradykinin
KW - Cerebral vessel
KW - Converting enzyme inhibitor
KW - Dogs
KW - Nitric oxide
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U2 - 10.1016/S0006-8993(00)02482-3
DO - 10.1016/S0006-8993(00)02482-3
M3 - Article
C2 - 10915812
AN - SCOPUS:0034604779
SN - 0006-8993
VL - 873
SP - 75
EP - 82
JO - Brain Research
JF - Brain Research
IS - 1
ER -