Reduced perivascular Po₂ increases nitric oxide release from endothelial cells

Abstract

Many studies have suggested that endothelial cells can act as "oxygen sensors" to large reductions in oxygen availability by increasing nitric oxide (NO) production. This study determined whether small reductions in oxygen availability enhanced NO production from in vivo intestinal arterioles, venules, and parenchymal cells. In vivo measurements of perivascular NO concentration ([NO]) were made with NO-sensitive microelectrodes during normoxic and reduced oxygen availability. During normoxia, intestinal first-order arteriolar [NO] was 397 +/- 26 nM (n = 5), paired venular [NO] was 298 +/- 34 nM (n = 5), and parenchymal cell [NO] was 138 +/- 36 nM (n = 3). During reduced oxygen availability, arteriolar and venular [NO] significantly increased to 695 +/- 79 nM (n = 5) and 534 +/- 66 nM (n = 5), respectively, whereas parenchymal [NO] remained unchanged at 144 +/- 34 nM (n = 4). During reduced oxygenation, arteriolar and venular diameters increased by 15 +/- 3% and 14 +/- 5%, respectively: NG-nitro-L-arginine methyl ester strongly suppressed the dilation to lower periarteriolar Po2. Micropipette injection of a CO2 embolus into arterioles significantly attenuated arteriolar dilation and suppressed NO release in response to reduced oxygen availability. These results indicated that in rat intestine, reduced oxygen availability increased both arteriolar and venular NO and that the main site of NO release under these conditions was from endothelial cells.

Vascular and perivascular nitric oxide release and transport: Biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3)

“…This relationship is consistent with some experimental reports [42]; however, reports of other experiments [43] have indicated that small reductions in perivascular PO 2 increase NO release. This apparent discrepancy could be explained by the phenomenon of the peak values of NOS1 catalysis.…”

Venular endothelium-derived NO can affect paired arteriole: a computational model

“…The model predictions of ϳ30% lower NO concentration in the venular endothelium compared with the arteriolar endothelium are also similar to the reported ϳ 25% lower NO concentration in paired venules and arterioles by Nase et al (32). Although the magnitude of the difference is similar, the NO concentration predicted in the present model is significantly different from the measured one.…”

“…Although the magnitude of the difference is similar, the NO concentration predicted in the present model is significantly different from the measured one. The predicted NO concentrations are in the range of 104 and 69 nM for the arteriolar and the venular endothelium, respectively ( Table 2, case 1), compared with a measured NO concentration of 397 and 298 nM, respectively (32). This high NO concentration can be obtained from the present model by 1) increasing endothelial NO release (see Fig.…”

Sodium channels are required during in vivo sodium chloride hyperosmolarity to stimulate increase in intestinal endothelial nitric oxide production

“…Carbon fiber, recessed-tip glass microelectrodes were used with a polarographic technique to measure [NO] in the intestine. NO-sensitive microelectrodes have been used in past studies in our laboratory (8,10,27). The production and calibration of the NO-sensitive microelectrodes were based on our lab's experience and techniques developed by Buerk and colleagues (13) and Freidemann et al (16).…”