Vasomotor Regulation of Coronary Microcirculation by Oxidative Stress: Role of Arginase

Abstract

Overproduction of reactive oxygen species, i.e., oxidative stress, is associated with the activation of redox signaling pathways linking to inflammatory insults and cardiovascular diseases by impairing endothelial function and consequently blood flow dysregulation due to microvascular dysfunction. This review focuses on the regulation of vasomotor function in the coronary microcirculation by endothelial nitric oxide (NO) during oxidative stress and inflammation related to the activation of L-arginine consuming enzyme arginase. Superoxide produced in the vascular wall compromises vasomotor function by not only scavenging endothelium-derived NO but also inhibiting prostacyclin synthesis due to formation of peroxynitrite. The upregulation of arginase contributes to the deficiency of endothelial NO and microvascular dysfunction in various vascular diseases by initiating or following oxidative stress and inflammation. Hydrogen peroxide, a diffusible and stable oxidizing agent, exerts vasodilator function and plays important roles in the physiological regulation of coronary blood flow. In occlusive coronary ischemia, the release of hydrogen peroxide from the microvasculature helps to restore vasomotor function of coronary collateral microvessels with exercise training. However, excessive production and prolonged exposure of microvessels to hydrogen peroxide impairs NO-mediated endothelial function by reducing L-arginine availability through hydroxyl radical-dependent upregulation of arginase. The redox signaling can be a double-edged sword in the microcirculation, which helps tissue survival in one way by improving vasomotor regulation and elicits oxidative stress and tissue injury in the other way by causing vascular dysfunction. The impact of vascular arginase on the development of vasomotor dysfunction associated with angiotensin II receptor activation, hypertension, ischemia-reperfusion, hypercholesterolemia, and inflammatory insults is discussed.

The Physiological Responses to 5000 m Open Water Swimming Exercise in Children

“…Another study, which has used the same swimming distance demonstrated that serum UA level, one of the non-enzymatic antioxidant marker, significantly increased in young adults. 24 In the present study, although UA didn't show any significant change after the swimming, the negative relationship between UA and WBC may support our opinion mentioned about the decrease in TOS. After the last 1000 m swim, WGLU and La levels significantly decreased from the start of the test (Table 1).…”

“…It is well documented that OS can inhibit NOS activity and decrease blood NO levels. 17,24,25,50 In the current study, it is not possible to claim that the increase of NOx was inhibited by OS during swimming, because in fact it did not changes significantly. The endothelial NO system is up-regulated after short durations training and it may be the mechanism that causes longer term structural changes that ultimately normalize shear stress and it may be return basal NO levels of sedentary individuals.…”

“…25 Increased superoxide levels may also lead to the conversion of NO to a stronger radical (such as peroxynitrite), 2 which impairs vasomotor function by decreasing the bioavailability of endothelium-derived NO and by inhibiting the synthesis of the vasodilator prostacyclin. 24 However, the physiological stress and OS levels of OWS on children and NOx's related to these parameters are unknown. Therefore, we hypothesized that 5000 m OWS will significantly increase physiological stress (PS), OS and blood NOx levels in children and that NOx can be associated with related to PS, OS and 5000 m swimming performance time.…”

“…But NO has both oxidant and antioxidant features depending on physiological conditions. 17,24 Moderate-intense aerobic exercises improve endothelial function; while high intensity exercises increase OS levels and affect endothelial function negatively, decreasing the bioavailability of NO. 25 Increased superoxide levels may also lead to the conversion of NO to a stronger radical (such as peroxynitrite), 2 which impairs vasomotor function by decreasing the bioavailability of endothelium-derived NO and by inhibiting the synthesis of the vasodilator prostacyclin.…”

Linking LOX-1 and Arginase II Through Mitochondria

“…Arginase II is expressed in endothelial and vascular smooth muscle cells and has been identified in many vascular beds including the aorta, coronary, carotid, and pulmonary arteries. 3,4 The exact function of vascular mitochondrial arginase II still remains elusive, although there is growing evidence suggesting that arginase inhibits nitric oxide (NO) synthesis by competing with NO synthase (NOS) for l-arginine, which is the exclusive substrate for NOS. 5 Inhibition of arginase stimulates NO production in endothelial cells, whereas overexpression of arginase II decreases intracellular l-arginine content and reduces NO production.…”