Decreased cardiac Ang-(1-7) is associated with salt-induced cardiac remodeling and dysfunction.
OBJECTIVE
Angiotensin II has a critical role in the regulation of blood pressure and cell growth and excess activity of the peptide is implicated in the pathogenesis of salt-induced cardiovascular injury. On the other hand, the role of counteracting angiotensin-(1-7) in cardiac structural and functional responses to high salt diet has not been elucidated. Therefore, the present study examined the changes in cardiac angiotensin-(1-7), its forming enzyme angiotensin converting enzyme 2 (ACE2) and receptor mas in response to a high salt diet in spontaneously hypertensive rats (SHR).


METHODS
Eight-week-old male spontaneously hypertensive rats (SHR) were given an 8% salt diet for 5 weeks (n = 8). Age- and gender-matched controls received standard chow (n = 6).


RESULTS
Salt excess increased arterial pressure (p < 0.05) and plasma renin and angiotensin II concentrations (p < 0.05). Salt-induced left ventricular remodeling and diastolic dysfunction were associated with diminished levels of angiotensin-(1-7) in the heart (p < 0.05) and no changes in cardiac angiotensin II levels. Exposure to high salt intake decreased cardiac ACE2 mRNA and protein level (p < 0.05). There was no difference in the protein levels of angiotensin II type 1 and mas receptors between the two experimental groups.


CONCLUSIONS
The adverse cardiac effects of excessive salt intake may result not only from the undesirable action of angiotensin II but may also be a consequence of diminished protective effects of the angiotensin-(1-7).
Varagic
Jasmina
J
Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. jvaragic@wfubmc.edu
Ahmad
Sarfaraz
S
Brosnihan
K Bridget
KB
Groban
Leanne
L
Chappell
Mark C
MC
Tallant
E Ann
EA
Gallagher
Patricia E
PE
Ferrario
Carlos M
CM
D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000097:blood; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001794:Blood Pressure; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012083:Renin / Q000097:blood; D017673:Sodium Chloride, Dietary / Q000633:toxicity*; D018487:Ventricular Dysfunction, Left / Q000209:etiology*; D020257:Ventricular Remodeling
D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D012083:Renin; C118790:angiotensin I (1-7)