Oxidative stress enhances the production and actions of adenosine in the kidney

Abstract

The purpose of this study was to determine whether superoxide anions (O.) activate 5'-nucleotidase (5'-ND), thereby increasing the production of renal adenosine and regulating renal function. Using HPLC analysis, we found that incubation of renal tissue homogenate with the O. donor KO(2) doubled adenosine production and increased the maximal reaction velocity of 5'-ND from 141 to 192 nmol. min(-1). mg protein(-1). The O.-generating system, xanthine/xanthine oxidase increased the maximal reaction velocity of 5'-ND from 122 to 204 nmol. min(-1). mg protein(-1). Superoxide dismutase (SOD) with catalase produced a concentration-dependent reduction of 5'-ND activity in renal tissue homogenate, while the SOD inhibitor diethyldithiocarbamic acid significantly increased 5'-ND activity. Inhibition of disulfide bond formation by thioredoxin or thioredoxin reductase significantly decreased xanthine/xanthine oxidase-induced activation of renal 5'-ND. In in vivo experiments, inhibition of SOD by diethyldithiocarbamic acid (0.5 mg. kg(-1). min(-1) iv) enhanced renal vasoconstriction induced by endogenously produced adenosine and increased renal tissue adenosine concentrations under control condition and in ischemia and reperfusion. We conclude that oxidative stress activates 5'-ND and increases adenosine production in the kidney and that this redox regulatory mechanism of adenosine production is important in the control of renal vascular tone and glomerular perfusion.

Adenosine A1-receptor deficiency diminishes afferent arteriolar and blood pressure responses during nitric oxide inhibition and angiotensin II treatment

“…2, D-E). In the end of ANG II treatment (days [11][12][13][14], blood pressure was significantly higher in wild-type mice than in the knockouts (Fig. 2F).…”

NO-independent mechanism mediates tempol-induced renal vasodilation in SHR

“…Another possibility is that oxidative stress might lead to increased renal production of adenosine (9). The increased adenosine levels may, in turn, lead to preglomerular vasoconstriction and elevated RVR (19).…”

“…The increased adenosine levels may, in turn, lead to preglomerular vasoconstriction and elevated RVR (19). Chen et al (9) found that treating kidney homogenate with the O 2 Ϫ donor KO 2 led to an increased V max of 5Ј-nucleotidase and doubling of adenosine production. Furthermore, SOD caused a concentration-dependent reduction of 5Ј-nucleotidase.…”

Nitric Oxide May Prevent Hypertension Early in Diabetes by Counteracting Renal Actions of Superoxide

“…The mechanism for superoxide-mediated vasoconstriction per se is not known and was not the focus of this study, but there is evidence that superoxide can affect thromboxane A 2 /PGH 2 receptor signaling 6,20,36,37 and other cell-signaling pathways in vascular smooth muscle 3,4,38 to cause vasoconstriction. In addition, Chen et al 39 reported that oxidative stress in the kidney increases production of adenosine, which is a powerful renal vasoconstrictor. The superoxide dismutase mimetic action of tempol also can lead to increased cyclooxygenase activity through metabolism of hydrogen peroxide, 3 and this may explain the increase in PG excretion that we measured in the tempol-treated rats.…”