1. In a new animal model which mimics the cellular events of early human atherosclerosis, atheroma-like lesions were produced by positioning a hollow silastic collar around the common carotid ...arteries of rabbits. The functional significance of these arterial lesions on blood flow responses to vasoactive agents was then studied in anaesthetized rabbits in vivo. 2. After 1 week of lesion development, resting blood flow was lower in atherosclerotic (cuffed) carotid arteries compared with the contralateral, sham-operated control arteries. 3. Intra-carotid injection of serotonin (0.01-1 microgram) produced dose-dependent increases in blood flow in control arteries, but produced either smaller increases or decreases in flow in cuffed arteries. Serotonin caused complete vasospasm (zero blood flow) in one of six rabbits. 4. Acetylcholine (0.0001-0.01 microgram, intra-carotid) produced smaller increases in blood flow in cuffed arteries compared with controls. 5. These data support the proposal that morphological and functional alterations in large arteries in the early stages of atherogenesis play an important role in determining blood flow in vivo. The increased vascular reactivity to serotonin which accompanies development of the lesions might contribute to vasospasm.
1. The vascular contractile effects of polymorphonuclear leucocytes (PMN) isolated from control rabbits and from rabbits made atherosclerotic by 1% cholesterol feeding for 8 weeks were examined. 2. ...Rings of control rabbit thoracic aorta with or without endothelium were mounted at 2 g tension in 10 mL organ baths and were submaximally contracted by phenylephrine (0.1 mumol/L). After 30 min incubation at 37 degrees C, the supernatant of PMN (5 x 10(7)/mL, in Tyrode solution containing 0.25% bovine serum albumin) was obtained by centrifugation for addition to the vascular preparation. 3. Control PMN supernatant (443 microL) caused contraction (0.58 +/- 0.15 g, n = 11) of phenylephrine-contracted aortic rings, which was prevented by removal of the endothelium (0.11 +/- 0.07 g, n = 5, P < 0.05). However, the control PMN supernatant had no contractile effect on aortic rings at resting tension (0.00 +/- 0.00 g, n = 8). 4. By comparison, atherosclerotic PMN supernatant (443 microL) caused a significantly greater contraction of the aortic rings (1.41 +/- 0.13 g, n = 9, P < 0.05 vs control PMN supernatant) that was only partly inhibited by removal of the endothelium (0.45 +/- 0.20 g, n = 9, P < 0.05). Moreover, PMN supernatants from four of seven atherosclerotic rabbits contracted aortic rings at resting tension (3.5 +/- 1.4 g, n = 7). 5. These results suggest that the release of a stable vasoconstrictor substance(s) by PMN is enhanced under conditions of atherosclerosis.
We tested the hypothesis that cerebral vasodilatation in response to arachidonate is dependent on activation of cyclooxygenase and cytochrome P-450 pathways and formation of endogenous reactive ...oxygen species and is mediated by activation of potassium channels. The diameter of cerebral arterioles was measured using cranial windows in anesthetized rats. Under control conditions baseline diameter = 45 ± 1 μm (mean ± SE), arachidonate (1-100 μM) and papaverine (10-50 μM) produced concentration-dependent vasodilatation. Cerebral vasodilator responses to arachidonate, but not papaverine, were abolished during topical application of indomethacin (10 μM, an inhibitor of cyclooxygenase) or catalase (100 U/ml, which inactivates hydrogen peroxide). In contrast, clotrimazole (10 μM) and 17-ODYA (20 μM), inhibitors of cytochrome P-450 activity, had no effect on dilator responses of cerebral arterioles to arachidonate. Superoxide dismutase (SOD, 100 U/ml) had no effect on vasodilator responses to papaverine or lower concentrations of arachidonate, whereas dilator responses to 100 μM arachidonate were inhibited modestly (by 22%) by SOD. Similarly, deferoxamine (1 mM) partly inhibited dilator responses to 10 and 100 μM arachidonate (by ∼30% at each concentration). Tetraethylammonium ion (1 mM) or iberiotoxin (50 nM), inhibitors of calcium-activated potassium channels, markedly inhibited vasodilatation in response to arachidonate (by 70-90%) but not papaverine. These findings suggest that dilatation of cerebral arterioles in response to arachidonate is mediated largely by endogenously formed reactive oxygen species, which are generated from cyclooxygenase activity, and activation of calcium-activated potassium channels. Thus activation of potassium channels appears to be a major mechanism of cerebral vasodilatation in response to reactive oxygen species produced endogenously.
Oxidative stress is a hallmark of all cardiovascular risk states (e.g. hypertension, diabetes, hypercholesterolemia, cigarette smoking) and a major underlying cause of endothelial dysfunction, ...vascular inflammation and blood vessel pathology. Under physiological conditions, cells of the vessel wall produce reactive oxygen species (ROS) such as superoxide (O2•–) and hydrogen peroxide (H2O2) in a deliberate and tightly regulated manner for use as second messengers in redox signalling pathways. However, in vascular pathophysiology, the production of ROS in vascular cells is elevated such that these molecules escape detoxification by cellular antioxidant pathways. When present at higher concentrations, ROS may undergo direct chemical interactions with other biomolecules. Of particular importance are the reactions between O2•– and nitric oxide (NO), which give rise to peroxynitrite (ONOO–), and the iron-catalysed Haber-Weiss reaction between O2 and H2O2, which gives rise to hydroxyl radicals (OH•).Peroxynitrite and OH• are extremely powerful oxidising species and, along with O2•– and H2O2, cause endothelial dysfunction through direct oxidative damage to cellular macromolecules, impairment of the NO signalling pathway, and activation of pro-inflammatory signalling cascades. Recent evidence suggests that the elevated ROS production in vascular pathophysiology is the result of a complex feed-forward mechanism whereby a primary source of ROS (NADPH oxidases) leads to dysfunction of endothelial nitric oxide synthase, xanthine oxidase and the mitochondrial electron transport chain, so that these enzymes become secondary sources of ROS and major contributors to vascular oxidative stress.
Full text
Available for:
FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This work gives an update to existing reconstructions of the Galactic Faraday rotation sky by processing almost all Faraday rotation data sets available at the end of the year 2020. Observations of ...extra-Galactic sources in recent years have, among other regions, further illuminated the previously under-constrained southern celestial sky, as well as parts of the inner disc of the Milky Way. This has culminated in an all-sky data set of 55,190 data points, which is a significant expansion on the 41,330 used in previous works, hence making an updated separation of the Galactic component a promising venture. The increased source density allows us to present our results in a resolution of about \(1.3\cdot 10^{-2}\, \mathrm{deg}^2\) (\(46.8\,\mathrm{arcmin}^2\)), which is a twofold increase compared to previous works. As for previous Faraday rotation sky reconstructions, this work is based on information field theory, a Bayesian inference scheme for field-like quantities which handles noisy and incomplete data. In contrast to previous reconstructions, we find a significantly thinner and pronounced Galactic disc with small-scale structures exceeding values of several thousand \(\mathrm{rad}\,\mathrm{m}^{-2}\). The improvements can mainly be attributed to the new catalog of Faraday data, but are also supported by advances in correlation structure modeling within numerical information field theory. We furthermore give a detailed discussion on statistical properties of the Faraday rotation sky and investigate correlations to other data sets.
PDF
