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The purpose of this investigation was to study the effect of the presence of red blood cells (RBCs) in the plasma layer near the arteriole wall on nitric oxide (NO) and oxygen (O2) transport. To this end, we extended a coupled NO and O2 diffusion-reaction model in the arteriole, developed by our group, to include the effect of the presence of RBCs in the plasma layer and the effect of convection. Two blood flow velocity profiles (plug and parabolic) were tested. The average hematocrit in the bloodstream was assumed to be constant in the central core and decreasing to zero in the boundary layer next to the endothelial surface layer. The effect of the presence or absence of RBCs near the endothelium was studied while varying the endothelial surface layer and boundary layer thickness. With RBCs present in the boundary layer, the model predicts that 1) NO decreases significantly in the endothelium and vascular wall; 2) there is a very small increase in endothelial and vascular wall Po2; 3) scavenging of NO by hemoglobin decreases with increasing thickness of the boundary layer; 4) the shape of the velocity profile influences both NO and Po2 gradients in the bloodstream; and 5) the presence of RBCs in the boundary layer near the endothelium has a much larger effect on NO than on O2 transport. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) regulates vascular tone and mitochondrial respiration. We investigated the hypothesis that there is reduced NO concentration in the renal cortex of diabetic rats that mediates reduced renal cortical blood perfusion and oxygen tension (P O2). Streptozotocin-induced diabetic and control rats were injected with l-arginine followed by Nomega-nitro-L-arginine-metyl-ester (L-NAME). NO and P O2 were measured using microsensors, and local blood flow was recorded by laser-Doppler flowmetry. Plasma arginine and asymmetric dimethylarginine (ADMA) were analyzed by high-performance liquid chromatography. L-Arginine increased cortical NO concentrations more in diabetic animals, whereas changes in blood flow were similar. Cortical P O2 was unaffected by L-arginine in both groups. L-NAME decreased NO in control animals by 87 +/- 15 nmol/l compared with 45 +/- 7 nmol/l in diabetic animals. L-NAME decreased blood perfusion more in diabetic animals, but it only affected P O2 in control animals. Plasma arginine was significantly lower in diabetic animals (79.7 +/- 6.7 vs. 127.9 +/- 3.9 mmol/l), whereas ADMA was unchanged. A larger increase in renal cortical NO concentration after l-arginine injection, a smaller decrease in NO after L-NAME, and reduced plasma arginine suggest substrate limitation for NO formation in the renal cortex of diabetic animals. This demonstrates a new mechanism for diabetes-induced alteration in renal oxygen metabolism and local blood flow regulation. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) and oxygen (02) transport in the microcirculation are coupled in a complex manner, since enzymatic production of NO depends on O2 availability, NO modulates vascular tone and O2 delivery, and tissue O2 consumption is reversibly inhibited by NO. The authors investigated whether NO bioavailability is influenced by the well-known Fåhraeus effect, which has been observed for over 70 years. This phenomenon occurs in small-diameter blood vessels, where the tube hematocrit is reduced below systemic hematocrit as a plasma boundary layer forms near the vascular wall when flowing red blood cells (rbcs) migrate toward the center of the bloodstream. Since hemoglobin iii the bloodstream is thought to be the primary scavenger of NO in vivo, this might have a significant impact on NO transport. To investigate this possibility, the authors developed a multilayered mathematical model for mass transport in arterioles using finite element numerical methods to simulate coupled NO and O2 transport in the blood vessel lumen, plasma layer, endothelium, vascular wall, and surrounding tissue. The Fahraeus effect was modeled by varying plasma layer thickness while increasing core hematocrit based on conservation of mass. Key findings from this study are that (1) despite an increase in the NO scavenging rate in the core with higher hematocrit, the model predicts enhanced vascular wall arid tissue NO bioavailability due to the relatively greater resistance for NO diffusion through the plasma layer; (2) increasing the plasma layer thickness also increases the resistance for O2 diffusion, causing a larger PO2 gradient near the vascular wall and decreasing tissue O2 availability, although this can be partially offset with inhibition of O2 consumption by higher tissue NO levels; (3) the Fåhraeus effect can become very significant in smaller blood vessels (diameters <30 µm); and (4) models that ignore the Fãhraeus effect may underestimate NO concentrations in blood and tissue. Objective: To examine whether prostaglandins are involved in endotheliurn-dependent vasodilatory responses of the skin microcirculation. Methods: Twenty-three young male volunteers were studied on 2 different days 1-3 weeks apart. On each experimental day the forearm skin blood flow response to iontophoretically applied acetylcholirie (Ach, an endothelium-dependent vasodilator) was determined with laser Doppler imaging following the intravenous administration of either the cyclo-oxygenase inhibitor lysine acetylsalicylate (L-AS), 900 mg, or the oral intake of indornethacin, 75 mg. Acetylcholine was iontophoresed both in presence and in absence of surface anesthesia. In some subjects, the effects of L-AS on skin reactive hyperemia were also assessed. Results: Acute cyclo-oxygenase inhibition with either drug influenced neither the skin blood flow response to 4 different doses of Ach (0.28, 1.4, 7, and 14 mC/cm²) nor reactive hyperemia. The peak vasodilatory response to Ach was significantly increased by skin anesthesia, regardless of whether the subjects received the cyclo-oxygenase inhibitor or not. For example, the mean response (+SD) to the largest dose of Ach (tested in 6 subjects, expressed in perfusion units) were as follows: in absence of anesthesia: L-AS 339 ± 105, placebo 344 ± 68; with anesthesia: L-AS 453 + 76, placebo 452 + 65 (p < .01 for effect of anesthesia). Conclusions: These data give no support for a contribution of prostaglandins to acetylcholine-induced vasodilation or to reactive hyperemia in the skin microcirculation. In this vascular bed, local anesthesia seems to amplify acetylcholine-induced vasodilation via a prostaglandin-independent mechanism. [ABSTRACT FROM AUTHOR]

Blood flow studies in the brain, heart, and other organs suggest that there could be interaction between nitric oxide (NO) and adenosine. This possibility was investigated in the optic nerve head (ONH) during photic stimulation of the dark-adapted cat eye. Functional activation of ONH blood flow was measured by laser Doppler flowmetry, simultaneously with NO and PO2 using double-barrel recessed electrochemical sensors. Photic stimulation (diffuse luminance flickering light at 30 Hz) increased ONH blood flow to 127.4 ± 4.7% (mean ± SEM) of baseline with a transient increase in NO by 79.8 ± 12.8 nM, while PO2 decreased from 24.5 ± 2.7 to 22.7 ± 2.4 Torr (control responses, 15 trials, 10 cats). Adenosine (3 mg/kg iv) increased baseline ONH blood flow to 113.8 ± 8.4% of control within 5 min. Functional activation of ONH blood flow was enhanced during photic stimulation, reaching a maximum of 155.8 ± 8.1% within 5 min, and remained enhanced for 30 to 45 min. NO responses during photic stimulation were not different from control responses. Treatment with a nonspecific NO synthase inhibitor (NG-nitro-l-arginine methyl ester, 40 mg/kg iv, 5 cats) did not alter the increase in resting ONH blood flow or the enhanced functional activation after adenosine. We conclude that there is no interaction between NO and adenosine during functional activation of cat ONH blood flow by photic stimulation. [Copyright &y& Elsevier]

Increased neuronal activity induced by diffuse flickering illumination of the ocular fundus generates increases in blood flow and decreases in tissue pO[sub 2] in the optic nerve head (ONH). This suggests that in the ONH, as in the brain, a coupling exists between function, perfusion, and metabolism, in accordance with the hypothesis of Roy and Sherrington. Following a review of the characteristics of the activity-induced blood flow response in the cat ONH, the relationship between blood flow and metabolism is discussed. We then examine possible mediators of the neurovascular coupling, some of the factors which may interfere with it, and point out various problems which remain to be addressed in order to better understand this coupling. [ABSTRACT FROM AUTHOR]

Looks at a study which examined the radial pO2 profiles in vivo for the periarteriolar tissue of the rat mesentery, using noninvasive phosphorescence quenching microscopy. Identification of the major function of the blood circulation; Regulation of the blood flow; Methodology used to conduct the study; Results of the study.