Angiotensin-(1-9) reverses experimental hypertension and cardiovascular damage by inhibition of the angiotensin converting enzyme/Ang II axis.
BACKGROUND
Little is known about the biological effects of angiotensin-(1-9), but available evidence shows that angiotensin-(1-9) has beneficial effects in preventing/ameliorating cardiovascular remodeling.


OBJECTIVE
In this study, we evaluated whether angiotensin-(1-9) decreases hypertension and reverses experimental cardiovascular damage in the rat.


RESULTS
Angiotensin-(1-9) (600  ng/kg per min for 2 weeks) reduced already-established hypertension in rats with early high blood pressure induced by angiotensin II infusion or renal artery clipping. Angiotensin-(1-9) also improved cardiac (assessed by echocardiography) and endothelial function in small-diameter mesenteric arteries, cardiac and aortic wall hypertrophy, fibrosis, oxidative stress, collagen and transforming growth factor type β - 1 protein expression (assessed by western blot). The beneficial effect of angiotensin-(1-9) was blunted by coadministration of the angiotensin type 2(AT2) receptor blocker PD123319 (36  ng/kg per min) but not by coadministration of the Mas receptor blocker A779 (100  ng/kg per min). Angiotensin-(1-9) treatment also decreased circulating levels of Ang II, angiotensin-converting enzyme activity and oxidative stress in aorta and left ventricle. Whereas, Ang-(1-9) increased endothelial nitric oxide synthase mRNA levels in aorta as well as plasma nitrate levels.


CONCLUSIONS
Angiotensin-(1-9) reduces hypertension, ameliorates structural alterations (hypertrophy and fibrosis), oxidative stress in the heart and aorta and improves cardiac and endothelial function in hypertensive rats. These effects were mediated by the AT2 receptor but not by the angiotensin-(1-7)/Mas receptor axis.
aDivision de Enfermedades Cardiovasculares, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago bMillennium Institute on Immunology and Immunotherapy cInstituto de Ciencias Biomedicas, Facultad de Medicina, Santiago dAdvanced Center for Chronic Diseases & Centro Estudios Moleculares de la Celula, Facultad Ciencias Quimicas y Farmaceuticas & Facultad Medicina, Universidad de Chile, Santiago, Chile eDepartment of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Maria Paz
MP
Ocaranza
Jackeline
J
Moya
Victor
V
Barrientos
Rodrigo
R
Alzamora
Daniel
D
Hevia
Cristobal
C
Morales
Melissa
M
Pinto
Nicolás
N
Escudero
Lorena
L
García
Ulises
U
Novoa
Pedro
P
Ayala
Guillermo
G
Díaz-Araya
Ivan
I
Godoy
Mario
M
Chiong
Sergio
S
Lavandero
Jorge E
JE
Jalil
Luis
L
Michea
D000803:Angiotensin I / Q000737:chemistry*; D000804:Angiotensin II / Q000737:chemistry*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D000818:Animals; D001011:Aorta / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000517:prevention & control; D004195:Disease Models, Animal; D004452:Echocardiography; D004730:Endothelium, Vascular / Q000473:pathology; D006352:Heart Ventricles; D006439:Hemodynamics; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000737:chemistry; D008297:Male; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; C506331:angiotensin I (1-9); D000804:Angiotensin II; C073402:PD 123319; D000803:Angiotensin I