Arginase inhibition reduces endothelial dysfunction and blood pressure rising in spontaneously hypertensive rats

Abstract

Our results showed that arginase inhibition reduced endothelial dysfunction and blood pressure rising in SHR.

Endothelial dysfunction in rat adjuvant‐induced arthritis: Up‐regulation of the vascular arginase pathway

“…In contrast, nor-NOHA had no effect on ACh-induced relaxation in control rats. These findings indicate that increased arginase contributes to endothelial dysfunction, probably by limiting the L-arginine availability for NOS, as previously observed in animal models of cardiovascular diseases (19)(20)(21)(22)24). It is noteworthy that beyond its effect on vascular NO production, decreased L-arginine availability secondary to arginase up-regulation might theoretically contribute to the eNOS uncoupling recently identified in vessels of AIA rats (12).…”

“…Arginase uses L-arginine (the substrate of NOS) as substrate and can thereby limit the availability of L-arginine for NO synthesis. Consistent with this theory are the studies demonstrating that arginase inhibition enhanced NOmediated vasodilatory function under pathologic conditions such as aging, hypertension, diabetes, and atherosclerosis (19)(20)(21)(22)(23)(24). Therefore, inhibition of vascular arginase activity might represent a new pharmacologic strategy for increasing availability of arginine for NO synthesis in conditions associated with endothelial dysfunction.…”

“…Because NOS and arginase use L-arginine as a common substrate, arginase may down-regulate NO biosynthesis by competing with NOS for L-arginine degradation. Consistent with this hypothesis, increased vascular arginase activity was reported to contribute to decreased endotheliumdependent NO production in pathologic conditions such as hypertension (19,20), atherosclerosis (21), diabetes (22), and erectile dysfunction (23), or in aging (24). Moreover, even though the regulating factors of arginase expression/activity remain largely unknown, it was demonstrated that various proinflammatory cytokines can act as inducers of arginase expression in cultured endothelial cells (18,25,26).…”

“…Arginase activity was determined in thoracic aorta according to the method of Corraliza et al (28), as previously described in detail (19). Briefly, frozen aortic tissue was pulverized and homogenized in lysis buffer (phos-phate buffered saline containing 1% sodium dodecyl sulfate, 2 mmoles/liter EDTA, 1 mmole/liter phenylmethylsulfonyl fluoride, 2 g/ml aprotinin, 2 g/ml leupeptin, and 1 g/ml pepstatin).…”

“…Thoracic aorta was excised, cleaned of connective tissue, and cut into rings of ϳ2 mm in length. Rings were suspended in Krebs solution (118 mmoles/ liter NaCl, 4.65 mmoles/liter KCl, 2.5 mmoles/liter CaCl 2 , 1.18 mmoles/liter KH 2 PO 4 , 24.9 mmoles/liter NaHCO 3 , 1.18 mmoles/liter MgSO 4 , 12 mmoles/liter glucose, pH 7.4), maintained at 37°C, and continuously aerated with 95% O 2 /5% CO 2 for isometric tension recording in organ chambers, as previously described (19). In some rings, endothelium was mechanically removed.…”