Reduced circulating levels of angiotensin-(1--7) in systemic sclerosis: a new pathway in the dysregulation of endothelial-dependent vascular tone control.
OBJECTIVE
Systemic sclerosis (SSc) impairs endothelium-dependent vasodilatation. Among angiotensin I (Ang I)-derived compounds, vasoconstrictor angiotensin II (Ang II) and vasodilator angiotensin-(1-7) (Ang-(1-7)), cleaved from ACE and neutral endopeptidase (NEP) 24.11, respectively, play an important role in vascular tone regulation. Ang-(1-7) may act independently or by activating other vasodilating molecules, such as nitric oxide (NO) or prostaglandin I2 (PGI2). Our aim was to assess, in patients with SSc, circulating levels of Ang I, Ang II and Ang-(1-7), with their metabolising enzymes ACE and NEP, and levels of NO and PGI2, and to correlate them to the main characteristics of SSc.


METHODS
Levels of Ang I, Ang II, Ang-(1-7), NEP, ACE, NO and PGI2 were measured in 32 patients with SSc, who were also assessed for humoral and clinical characteristics, and 55 controls.


RESULTS
Plasma Ang I, Ang II and Ang-(1-7) levels were lower in patients with SSc than in controls (p<0.001in all cases). When Ang II and Ang-(1-7) levels were expressed as a function of the available Ang I, lower Ang-(1-7) levels in patients with SSc than in controls were confirmed (p<0.001), while no difference was found for Ang II levels. In patients with SSc, the Ang II/Ang-(1-7) ratio indicated a prevalence of Ang II over Ang-(1-7), while in controls Ang-(1-7) was prevalent (p<0.001). Levels of ACE, NEP, NO and PGI2 were lower in patients with SSc than in controls (p<0.05 in all cases).


CONCLUSIONS
In patients with SSc, prevalence of the vasoconstricting Ang II over the vasodilator Ang-(1-7) suggests a dysfunction of the angiotensin-derived cascade that may contribute to dysregulation of vascular tone.
Pignone
Alberto
A
Department of Medicine and Surgery, Division of Medicine I and II and Rheumatology, Villa Monna Tessa, University of Florence, Florence, Italy.
Rosso
Angela Del
AD
Brosnihan
K Bridget
KB
Perfetto
Federico
F
Livi
Riccardo
R
Fiori
Ginevra
G
Guiducci
Serena
S
Cinelli
Marina
M
Rogai
Veronica
V
Tempestini
Alessio
A
Bartoli
Francesca
F
Generini
Sergio
S
Ferrario
Carlos M
CM
Cerinic
Marco Matucci
MM
D000803:Angiotensin I / Q000097:blood*; D000804:Angiotensin II / Q000097:blood*; D000959:Antihypertensive Agents / Q000097:blood; D011464:Epoprostenol / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D010446:Peptide Fragments / Q000097:blood*; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D012595:Scleroderma, Systemic / Q000097:blood*; D014662:Vasoconstrictor Agents / Q000097:blood
D000959:Antihypertensive Agents; D010446:Peptide Fragments; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide; D000803:Angiotensin I; D011464:Epoprostenol; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin; C118790:angiotensin I (1-7)