Microvascular oxygen tension in the rat mesentery

Extracellular purines and pyrimidines have major effects on cardiac rhythm and contraction. ATP/UTP are released during various physiopathological conditions, such as ischemia, and despite degradation by ectonucleotidases, their interstitial concentrations can markedly increase, a fact that is clearly associated with arrhythmia. In the present whole cell patch-clamp analysis on ventricular cardiomyocytes isolated from various mammalian species, ATP and UTP elicited a sustained, nonselective cationic current, I(ATP). UDP was ineffective, whereas 2'(3')-O-(4-benzoylbenzoyl)-ATP was active, suggesting that P2Y(2) receptors are involved. I(ATP) resulted from the binding of ATP(4-) to P2Y(2) purinoceptors. I(ATP) was maintained after ATP removal in the presence of guanosine 5'-[gamma-thio]triphosphate and was inhibited by U-73122, a PLC inhibitor. Single-channel openings are rather infrequent under basal conditions. ATP markedly increased opening probability, an effect prevented by U-73122. Two main conductance levels of 14 and 23 pS were easily distinguished. Similarly, in fura-2-loaded cardiomyocytes, Mn(2+) quenching and Ba(2+) influx were significant only in the presence of ATP or UTP. Adult rat ventricular cardiomyocytes expressed transient receptor potential channel TRPC1, -3, -4, and -7 mRNA and the TRPC3 and TRPC7 proteins that coimmunoprecipitated. Finally, the anti-TRPC3 antibody added to the patch pipette solution inhibited I(ATP). In conclusion, activation of P2Y(2) receptors, via a G protein and stimulation of PLCbeta, induces the opening of heteromeric TRPC3/7 channels, leading to a sustained, nonspecific cationic current. Such a depolarizing current could induce cell automaticity and trigger the arrhythmic events during an early infarct when ATP/UTP release occurs. These results emphasize a new, potentially deleterious role of TRPC channel activation.     

Effect of convective flow on the oxygen tension profile in the cornea

The effect of convective flow on the distribution of a diffusing substance that is being consumed is analyzed. For the mammalian cornea, one of the few tissues where convection, diffusion and consumption simultaneously exist, the effect of convection on the distribution of oxygen is shown to be small.     

Influence of oxygen tension on the physiology ofSaccharomyces cerevisiae in continuous culture

The effect of decreasing oxygen tensions on the physiology and composition ofSaccharomyces cerevisiae was studied in galactose-limited continuous cultures. Between oxygen tensions of 75 and 3 mm Hg the metabolism of galactose was oxidative and cell composition constant. Below 3 mm Hg a more fermentative metabolism was operative resulting in low cell yields and accumulation of ethanol in culture filtrates. This correlated with an increased alcohol dehydrogenase and a decreased particulate NADH oxidase activity of cell extracts. While the cellular contents of RNA and protein were not altered at low oxygen tensions there were marked changes in those of carbohydrates and lipids. Below 3 mm Hg there were decreases in most lipid constituents but those of membrane constituents such as sterol esters and phosphatides together with unsaturated fatty acids were most evident. ATP pool size was lowest and amino acid pool size highest at low oxygen tensions. The increased amino acid pool size was due to higher concentrations of arginine and aspartate.This work was supported by grant B/SR/5780 from the Science Research Council. We are grateful to the Brewers Society for a research studentship to B. Johnson. We thank Mr. A. Bradley and Mrs. C. Jones for competent technical assistance.     

Effect of oxygen tension on chromosomal aberrations in Fanconi anaemia

Blood samples from four healthy individuals and from seven Fanconi anaemia (FA) patients were cultured at oxygen tensions ranging from 3% to 45% O2. Cultures were harvested at 72 h and scored for chromosomal aberrations. In the majority of FA patients the aberration frequency showed a tendency to increase as a function of oxygen tension over the culture, whereas the aberration frequency in healthy individuals was not affected. However, the response in FA cultures was variable among patients and in individual cases when assayed on different occasions. A much stronger effect of oxygen tension was observed when the FA blood samples had been treated with mitomycin C (0.25 microgram/ml, 30 min) before culture initiation.     

Transmural gradients of oxygen tension on cerebral microvessels in rats

Using modified oxygen needle microelectrodes, vital microscopy with video-recording facilities, measurements of tissue oxygen tension (PO2) profiles near the cortical arterioles and transmural PO2 gradients on pial arterioles of the rat were performed. At control transmural PO2 gradient averaged 1.17 +/- 0.06 mm Hg/microm (mean +/- SEM, n = 40). Local dilatation of the arteriolar wall (microapplication of sodium nitroprusside approximately 2 x 10(-7) M) resulted in marked drop of the transmural PO2 gradient to 0.68 +/- 0.04 mm Hg/microm (p < 0.001, n = 38). The important finding of the study is the dependence of the transmural PO2 gradient on the vascular tone of pial arterioles. The data presented allow to conclude that O2 consumption of the arteriolar wall lies within the range for surrounding tissue and O2 consumption of the endothelial layer and, apparently, has no substantial impact on transmural PO2 gradient.     

Microlymphatic and tissue oxygen tension in the rat mesentery

Oxygen phosphorescence quenching was used to measure tissue Po(2) of lymphatic vessels of 43.6 +/- 23.1 microm (mean +/- SD) diameter in tissue locations of the rat mesentery classified according to anatomic location. Lymph and adipose tissue Po(2) were 20.6 +/- 9.1 and 34.1 +/- 7.8 mmHg, respectively, with the difference being statistically significant. Rare microlymphatic vessels in connective tissue not surrounded by microvessels had a Po(2) of 0.8 +/- 0.2 mmHg, whereas the surrounding tissue Po(2) was 3.0 +/- 3.2 mmHg, with both values being significantly lower than those of adipose tissue. Lower of lymph fluid Po(2) relative to the surrounding tissue was also evident in paired measurements of Po(2) in the lymphatic vessels and perilymphatic adipose tissue, which was significantly lower than the Po(2) in paired adipose tissue. The Po(2) of the lymphatic fluid of the mesenteric microlymphatics is consistently lower than that of the surrounding adipose tissue by approximately 11 mmHg; therefore, lymph fluid has the lowest Po(2) of this tissue. The disparity between lymph and tissue Po(2) is attributed to the microlymphatic vessel wall and lymphocyte oxygen consumption.