Dependence of intestinal arteriolar regulation on flow-mediated nitric oxide formation

2000 ◽  
Vol 279 (5) ◽  
pp. H2249-H2258 ◽  
Author(s):  
H. Glenn Bohlen ◽  
Geoffrey P. Nase

Our hypothesis was that a large fraction of resting nitric oxide (NO) formation is driven by flow-mediated mechanisms in the intestinal microvasculature of the rat. NO-sensitive microelectrodes measured the in vivo perivascular NO concentration ([NO]). Flow was increased by forcing the arterioles to perfuse additional nearby arterioles; flow was decreased by lowering the mucosal metabolic rate by reducing sodium absorption. Resting periarteriolar [NO] of large arterioles (first order; 1A) and intermediate-sized arterioles (second order; 2A) was 337 ± 20 and 318 ± 21 nM. The resting [NO] was higher than the dissociation constant for the NO-guanylate cyclase reaction of vascular smooth muscle; therefore, resting [NO] should be a potent dilatory signal at rest. Over flow velocity and shear rate ranges of ∼40–180% of control, periarteriolar [NO] changed 5–8% for each 10% change in flow velocity and shear rate. The relationship of [NO] to flow velocity and shear rate demonstrated that 60–80% of resting [NO] depended on flow-mediated mechanisms. Therefore, moment-to-moment regulation of [NO] at rest is an ongoing process that is highly dependent on flow-dependent mechanisms.

2004 ◽  
Vol 286 (2) ◽  
pp. H492-H497 ◽  
Author(s):  
H. Glenn Bohlen

In severe obesity, microvascular endothelial regulation of nitric oxide (NO) formation is compromised in response to muscarinic stimulation, and major arteries have suppressed flow-mediated dilation. Because normal microvessels are highly dependent on flow-mediated stimulation of NO generation and are responsive to intra- and extravascular oxygen availability, they are likely a major site of impaired endothelial regulation. This study evaluated the blood flow and oxygen-dependent aspects of intestinal microvascular regulation and NO production in Zucker obese rats just before the onset of hyperglycemia. Ruboxistaurin (LY-333531) was used to inhibit PKC-βII to determine whether flow or oxygen-related NO regulation was improved. Blood flow velocity was increased by forcing arterioles to perfuse ∼50% larger tissue areas by occlusion of nearby arterioles, and oxygen tension in the bath was lowered to create a modest oxygen depletion. When compared with lean Zucker rats, the periarteriolar NO concentration ([NO]) for obese rats was ∼30% below normal. At elevated shear rates, the [NO] for arterioles of obese animals was 20–30% below those in the arterioles of lean rats, and the NO response to decreased oxygen was about half normal in obese rats. All of these regulatory problems were essentially corrected in obese rats by PKC blockade with only minor changes in the microvascular behavior in lean rats. Therefore, activation of PKC-βII in endothelial cells during obesity suppressed NO regulation both at rest and in response to increased flow velocity and decreased oxygen availability.


Membranes ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 299
Author(s):  
Monica De Caroli ◽  
Fabrizio Barozzi ◽  
Luciana Renna ◽  
Gabriella Piro ◽  
Gian-Pietro Di Sansebastiano

Plants rely on both actin and microtubule cytoskeletons to fine-tune sorting and spatial targeting of membranes during cell growth and stress adaptation. Considerable advances have been made in recent years in the comprehension of the relationship between the trans-Golgi network/early endosome (TGN/EE) and cytoskeletons, but studies have mainly focused on the transport to and from the plasma membrane. We address here the relationship of the cytoskeleton with different endoplasmic reticulum (ER) export mechanisms toward vacuoles. These emergent features of the plant endomembrane traffic are explored with an in vivo approach, providing clues on the traffic regulation at different levels beyond known proteins’ functions and interactions. We show how traffic of vacuolar markers, characterized by different vacuolar sorting determinants, diverges at the export from the ER, clearly involving different components of the cytoskeleton.


2013 ◽  
Vol 304 (4) ◽  
pp. H559-H566 ◽  
Author(s):  
Ashkan Javadzadegan ◽  
Andy S. C. Yong ◽  
Michael Chang ◽  
Austin C. C. Ng ◽  
John Yiannikas ◽  
...  

Flow recirculation zones and shear rate are associated with distinct pathogenic biological pathways relevant to thrombosis and atherogenesis. The interaction between stenosis severity and lesion eccentricity in determining the length of flow recirculation zones and peak shear rate in human coronary arteries in vivo is unclear. Computational fluid dynamic simulations were performed under resting and hyperemic conditions on computer-generated models and three-dimensional (3-D) reconstructions of coronary arteriograms of 25 patients. Boundary conditions for 3-D reconstructions simulations were obtained by direct measurements using a pressure-temperature sensor guidewire. In the computer-generated models, stenosis severity and lesion eccentricity were strongly associated with recirculation zone length and maximum shear rate. In the 3-D reconstructions, eccentricity increased recirculation zone length and shear rate when lesions of the same stenosis severity were compared. However, across the whole population of coronary lesions, eccentricity did not correlate with recirculation zone length or shear rate ( P = not signficant for both), whereas stenosis severity correlated strongly with both parameters ( r = 0.97, P < 0.001, and r = 0.96, P < 0.001, respectively). Nonlinear regression analyses demonstrated that the relationship between stenosis severity and peak shear was exponential, whereas the relationship between stenosis severity and recirculation zone length was sigmoidal, with an apparent threshold effect, demonstrating a steep increase in recirculation zone length between 40% and 60% diameter stenosis. Increasing stenosis severity and lesion eccentricity can both increase flow recirculation and shear rate in human coronary arteries. Flow recirculation is much more sensitive to mild changes in the severity of intermediate stenoses than is peak shear.


2018 ◽  
Vol 616 ◽  
pp. A76 ◽  
Author(s):  
Marko Sestovic ◽  
Brice-Olivier Demory ◽  
Didier Queloz

Context. As of today, hundreds of hot Jupiters have been found, yet the inflated radii of a large fraction of them remain unexplained. A number of mechanisms have been proposed to explain these anomalous radii, however most of these can only work under certain conditions and may not be sufficient to explain the most extreme cases. It is still unclear whether a single mechanism can sufficiently explain the entire distribution of radii, or whether a combination of these mechanisms is needed. Aims. We seek to understand the relationship of radius with stellar irradiation and mass and to find the range of masses over which hot Jupiters are inflated. We also aim to find the intrinsic physical scatter in their radii, caused by unobservable parameters, and to constrain the fraction of hot Jupiters that exhibit inflation. Methods. By constructing a hierarchical Bayesian model, we inferred the probabilistic relation between planet radius, mass, and incident flux for a sample of 286 gas giants. We separately incorporated the observational uncertainties of the data and the intrinsic physical scatter in the population. This allowed us to treat the intrinsic physical scatter in radii, due to latent parameters such as the heavy element fraction, as a parameter to be inferred. Results. We find that the planetary mass plays a key role in the inflation extent and that planets in the range ~0.37−0.98  MJ show the most inflated radii. At higher masses, the radius response to incident flux begins to decrease. Below a threshold of 0.37 ± 0.03  MJ we find that giant exoplanets as a population are unable to maintain inflated radii ≿1.4  RJ but instead exhibit smaller sizes as the incident flux is increased beyond 106 W m−2. We also find that below 1  MJ, there is a cut-off point at high incident flux beyond which we find no more inflated planets, and that this cut-off point decreases as the mass decreases. At incident fluxes higher than ~1.6 × 106 W m−2 and in a mass range 0.37−0.98  MJ, we find no evidence for a population of non-inflated hot Jupiters. Our study sheds a fresh light on one of the key questions in the field and demonstrates the importance of population-level analysis to grasp the underlying properties of exoplanets.


1996 ◽  
Vol 1996 ◽  
pp. 111-111
Author(s):  
V.C. Flamarique ◽  
R.M. Lewis ◽  
G. Simm

Excess fat in lamb is regarded as an important reason for less lamb meat being purchased by consumers. This has encouraged the development and use (particularly in Terminal Sire breeds) of selection indices that can identify animals that will sire leaner progeny. These indices usually include live weight and in vivo predictors of body composition, such as an ultrasonic measurement of muscle and fat depth, as selection criteria (Simm and Dingwall, 1989). But the usefulness of such in vivo measurements as predictors of carcass composition depends on the correlation between, and the variation in, live and carcass measures. The objectives of this study were to determine the strength of the relationship between ultrasound and dissection measures of carcass composition, and the degree of genetic variation in these measures, in crossbred progeny of Suffolk rams.


2018 ◽  
Vol 67 (2) ◽  
pp. 338-345 ◽  
Author(s):  
Jianshuang Li ◽  
Tong Li ◽  
Shuo Li ◽  
Lipeng Xie ◽  
Yi-Lin Yang ◽  
...  

Previous studies have demonstrated that CXCL12/CXCR4 axis is closely related to tumors such as malignant pleural mesothelioma (MPM). This research was conducted in order to detect whether CXCL12/CXCR4 inhibitors could restrain MPM and have a synergistic effect with chemotherapy, also to investigate the relationship of CXCL12/CXCR4 with other gene expressions in MPM. Forty mice were injected MPM cells and randomly divided into four groups: the PBS (control group), AMD3100 (CXCR4-CXCL12 antagonist), pemetrexed and AMD3100 plus pemetrexed. The mice were treated respectively for duration of 3 weeks. The size, bioluminescence and weight of tumors were measured. The differences between gene expressions in each group were analyzed. The tumor weights of each treatment group were lower than that of the control group (p<0.05). The bioluminescence of the tumor of the AMD3100 treatment group and the AMD3100 plus pemetrexed treatment group were lower than that of the control group (p<0.05), and AMD3100 was shown to have synergistic effects with pemetrexed (p<0.05). Among the 2.5 billion genes, several hundreds of genes expressed differently between groups. Results show that AMD3100 and pemetrexed can inhibit the growth of MPM in vivo, also that there is a better result if both are used together. Our findings suggest that CXCL12/CXCR4 axis affects a certain amount of gene expression in MPM.


1977 ◽  
Vol 43 (5) ◽  
pp. 839-843 ◽  
Author(s):  
J. A. Severson ◽  
R. D. Fell ◽  
J. G. Tuig ◽  
D. R. Griffith

Plasma corticosterone concentrations and in vitro adrenal secretion of corticosterone were determined in exercise-trained rats. Rats, 100, 200, and 300 days of age, were trained for a 10-wk period by treadmill running. Following the training program, rats were subjected to an acute bout of swimming. Acute swimming elevated plasma corticosterone concentrations in all age groups. At 170 days of age, the plasma corticosterone concentration following swimming was higher in exercise-trained rats than in controls. The opposite was true of acutely swum rats at 270 and 370 days of age. Acute swimming elevated the in vitro adrenal gland response to adrenocorticotropic hormone stimulation in control rats at all ages and in trained rats at 170 days of age. The in vivo relationship of epinephrine and the pituitary adrenal system is suggested as a mechanism which could have caused this response. The relationship of secretion rates to plasma corticosterone concentrations indicated that extra-adrenal mechanisms, such as decreased turnover, were also responsible for the elevated plasma corticosterone levels observed in response to acute swimming.


2017 ◽  
Vol 313 (6) ◽  
pp. H1249-H1260 ◽  
Author(s):  
Mohammad S. Razavi ◽  
Tyler S. Nelson ◽  
Zhanna Nepiyushchikh ◽  
Rudolph L. Gleason ◽  
J. Brandon Dixon

The intrinsic contraction of collecting lymphatic vessels serves as a pumping system to propel lymph against hydrostatic pressure gradients as it returns interstitial fluid to the venous circulation. In the present study, we proposed and validated that the maximum opposing outflow pressure along a chain of lymphangions at which flow can be achieved increases with the length of chain. Using minimally invasive near-infrared imaging to measure the effective pumping pressure at various locations in the rat tail, we demonstrated increases in pumping pressure along the length of the tail. Computational simulations based on a microstructurally motivated model of a chain of lymphangions informed from biaxial testing of isolated vessels was used to provide insights into the pumping mechanisms responsible for the pressure increases observed in vivo. These models suggest that the number of lymphangions in the chain and smooth muscle cell force generation play a significant role in determining the maximum outflow pressure, whereas the frequency of contraction has no effect. In vivo administration of nitric oxide attenuated lymphatic contraction, subsequently lowering the effective pumping pressure. Computational simulations suggest that the reduction in contractile strength of smooth muscle cells in the presence of nitric oxide can account for the reductions in outflow pressure observed along the lymphangion chain in vivo. Thus, combining modeling with multiple measurements of lymphatic pumping pressure provides a method for approximating intrinsic lymphatic muscle activity noninvasively in vivo while also providing insights into factors that determine the extent that a lymphangion chain can transport fluid against an adverse pressure gradient. NEW & NOTEWORTHY Here, we report the first minimally invasive in vivo measurements of the relationship between lymphangion chain length and lymphatic pumping pressure. We also provide the first in vivo validation of lumped parameter models of lymphangion chains previously developed through data obtained from isolated vessel testing.


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