Increased arginase levels in heart failure represent a therapeutic target to rescue microvascular perfusion.
OBJECTIVE
Heart failure (HF) is defined as the incapability of the heart to serve the tissues adequately with blood. This includes changes in microvascular perfusion. A mechanism aggravating perfusion disturbances in HF is endothelial dysfunction by reduced bioavailability of nitric oxide (NO). A mechanism possibly contributing to low NO bioavailability is the upregulation of arginase. Therefore, we investigated circulating arginase levels in patients with HF and its consequences for microvascular perfusion.


METHODS
A first group consisted of eighty patients with chronic HF. Patients were characterized by echocardiography and laboratory values. Arginase 1 levels were determined using a commercially available ELISA. A second experimental group included eight patients with severe heart failure. Using sidestream darkfield intravital microscopy sublingual microcirculation was quantified before and after the topical incubation of nor-NOHA as arginase inhibitor and L-NMMA as NO synthase inhibitor.


RESULTS
Circulating arginase-1 levels were significantly higher in patients with heart failure compared to controls (p < 0.001). Patients with severe heart failure (NYHA III/IV) had significantly higher arginase-1 levels compared to patients with mild heart failure (p < 0.01, NYHA I/II). Sublingual perfused capillary density increased significantly (p < 0.01) following incubation with nor-NOHA. However, this effect was abolished when nor-NOHA was co-incubated with L-NMMA.


CONCLUSIONS
In conclusion, circulating arginase 1 levels are elevated in patients with HF. A topical inhibition of arginase in these patients leads to improved microcirculation by a NO dependent mechanism. Inhibition of arginase is a possible therapeutic target to rescue microcirculation in patients with HF.
Clinic of Internal Medicine I, Friedrich-Schiller-University, Erlanger Allee 11, Jena, Germany.
Felix
F
Quitter
Hans R
HR
Figulla
Markus
M
Ferrari
John
J
Pernow
Christian
C
Jung
D000368:Aged; D001119:Arginase / Q000097:blood*; D004452:Echocardiography; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged
D001119:Arginase