Effects Of Intraluminal Pressure Research Articles

High intraluminal pressure promotes vascular inflammation via caveolin-1

The aetiology and progression of hypertension involves various endogenous systems, such as the renin angiotensin system, the sympathetic nervous system, and endothelial dysfunction. Recent data suggest that vascular inflammation may also play a key role in the pathogenesis of hypertension. This study sought to determine whether high intraluminal pressure results in vascular inflammation. Leukocyte adhesion was assessed in rat carotid arteries exposed to 1 h of high intraluminal pressure. The effect of intraluminal pressure on signaling mechanisms including reactive oxygen species production (ROS), arginase expression, and NFĸB translocation was monitored. 1 h exposure to high intraluminal pressure (120 mmHg) resulted in increased leukocyte adhesion and inflammatory gene expression in rat carotid arteries. High intraluminal pressure also resulted in a downstream signaling cascade of ROS production, arginase expression, and NFĸB translocation. This process was found to be angiotensin II-independent and mediated by the mechanosensor caveolae, as caveolin-1 (Cav1)-deficient endothelial cells and mice were protected from pressure-induced vascular inflammatory signaling and leukocyte adhesion. Cav1 deficiency also resulted in a reduction in pressure-induced glomerular macrophage infiltration in vivo. These findings demonstrate Cav1 is an important mechanosensor in pressure-induced vascular and renal inflammation.

Effects of Intraluminal Pressure on Motility in the Crop and Gizzard of the Earthworm, Lumbricus terrestris

The present study was designed to examine motility in the isolated earthworm gut. The physiological significance of, environmental stimuli that trigger, and cellular and molecular basis of gut motility in this species are unclear. Earthworms (Canadian Nightcrawlers) were obtained from a local fishing bait supplier. Worms were kept at 4 °C until the day of study. Worms were housed in worm bedding until 2–7 days prior to experimentation, at which time they were transferred into a petri dish lined with a water‐moistened paper towel to allow the gut to be partially emptied. On the day of study, worms were anesthetized by placing them in a beaker containing 200 ml of tap water and 1–2 Alka‐Seltzer tablets. Anesthetized worms were dissected, and the crop and gizzard was removed en bloc, cleaned of adhering septal and connective tissue, and transferred to a tissue bath containing worm saline at room temperature (~20 °C). The gut preparation was cannulated at both ends using 20G stainless steel hypodermic tubing. The lumen was filled with worm saline. The distal cannula was connected to a pressure transducer and closed by a stopcock. The proximal cannula was connected to a 30 ml syringe filled with worm saline that was open to atmospheric pressure. The height of the syringe could be raised and lowered to control intraluminal pressure. The preparation was equilibrated at ambient pressure for approximately 30 minutes. Following equilibration, intraluminal pressure was elevated incrementally every 5–10 minutes. A camera placed above the tissue bath recorded video (30 frames per second) during each pressure maneuver. The video was analyzed off line using a custom spatiotemporal mapping algorithm to assess luminal diameter. We found that the gut exhibited very low amplitude (<1 mmHg) pressure fluctuations at ambient pressure, and these pressure fluctuations were associated with waves of constriction/dilation in the gut lumen. Raising intraluminal pressure slightly from 0 to 2 mmHg induced a robust motor response such that the organ first passively dilated in response to the increase in intraluminal pressure, and then both gut regions constricted by up to 30%. The constrictions were followed by dilations, and this pattern continued, such that motility appeared as phasic waves of constriction/dilation. These robust phasic motor patterns were associated with large amplitude (20 mmHg) pressure pulsations. Larger motor events were in phase with larger pressure pulsations, and smaller motor events occurred in phase with smaller pressure pulsations. At higher intraluminal pressures (10 mmHg), the gut passively dilated, and motor events ceased, while intraluminal pressure passively tracked the applied hydrostatic pressure with no further pressure pulsations. Thus, we conclude that the earthworm crop/gizzard exhibits a robust mechanical response that is triggered by distention of the organ wall occurring with elevated intraluminal pressure. This response is likely to be of physiological significance, and may underlie peristalsis and propulsion of luminal contents in this species. The cellular and chemical basis of this response is not known.Support or Funding InformationSupport provided by Med Associates and Catamount Research and Development.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

L-Arginine and L-Nitroarginine Methylester Effects on Vasomotion in Isolated Rabbit Eyes

Background/Aims: Although nitric oxide (NO) has been shown to be essential for maintaining the basal blood flow in the retina and optic nerve head, its exact role in vasomotion is still controversial. This study investigated L-arginine (L-Arg) and N-nitro-L-arginine methylester (L-NAME) effects on vascular reactivity in a model of isolated rabbit eye. Methods: Rabbit external ophthalmic arteries (n = 12) in a head-mounted preparation were cannulated and perfused with warmed Tyrode solution. The effect of intraluminal pressure as a measure of total vascular resistance was assessed. Response curves to intra-arterial injections of 3 growing concentrations of L-Arg (n = 6) and L-NAME (n = 6) were obtained. Results: Without any drug administration, spontaneous oscillations were observed in all the models. L-Arg (NO precursor) induced vasodilation and decreased both frequency and amplitude of the periodic oscillations. L-NAME (NO synthase inhibitor) produced a strong vasoconstrictor tone and stimulated vasomotion, causing a faster rate of pulsatility. Conclusion:L-Arg and L-NAME acted as modulators of ocular vascular tone. L-Arg elicited vasodilation and decreased vasomotion while L-NAME produced a strong vasoconstrictor tone and caused a faster rate of pulsatility. These findings justify the need to investigate NO precursors and antagonists as possible alternative therapeutics in vascular eye diseases.

Endothelin-1 effects on spontaneous oscillations in choroidal arterioles

This study characterizes the effects of endothelin-1 (ET-1) on the perfusion pressure of the choroidal vasculature using in situ perfused isolated rabbit eyes. Rabbit external ophthalmic arteries (n = 12) in a head-mounted preparation were cannulated and perfused with warmed tyrode. The three-way polypropylene catheter was further connected to a pressure transducer and the effect of intraluminal pressure as a measure of total vascular resistance was assessed. Response curves to intra-arterial injections of ET-1 (group A; n = 6) and to an intravitreal injection followed by an intra-arterial injection of ET-1 (group B; n = 6) were obtained. Data were studied using paired t-test and fast Fourier transform. Before any drugs were administered, spontaneous oscillations were observed in the 12 rabbit models. In group A, ET-1 induced a short and weak vasodilating effect followed by a strong and long-lasting vasoconstrictor tone. Vasomotion became more evident, showing a higher frequency and shorter amplitude of oscillations. In group, B the intravitreal injection produced no significant changes in registered pressure or vasomotion characteristics. The intra-arterial injection produced effects similar to those observed in group A. Our study has three main findings: (i) the choroidal vasculature demonstrated spontaneous oscillations in perfusion pressure in basal conditions in all rabbit eye models; (ii) ET-1 applied intra-arterially induced a short drop in perfusion pressure followed by a long withstanding contraction; and (iii) intra-arterial ET-1 modulated the frequency and amplitude of the spontaneous oscillations, causing a faster rate of pulsatility.

Effect of intraluminal pressure and tone on smooth muscle Ca2+ oscillations in cremaster muscle arterioles

Arteriolar smooth muscle cells exhibit local variation in intracellular Ca2+ (Ca2+i) levels as shown by phenomena such as sparks, flashes and waves. The exact relationship of such events to levels of intraluminal pressure and myogenic tone, however, remains unclear. Using Fluo 4 (10 μM) loaded and cannulated rat cremaster muscle arterioles, the present studies examined variations in Ca2+i levels. Changes in fluorescence were measured using a spinning disk confocal system coupled to a microscope (x60, 1.2 N.A. objective) and high speed intensified CCD. Measurements of Ca2+i were collected at 30Hz and regions of interest defined within single cells of the vessel wall. Measurements were taken at 10, 40, 70 and 100 mmHg under baseline conditions and following treatment with nifedipine (1 μM) or adenosine (10μM). Under control conditions, increasing intraluminal pressure (10 – 70 mmHg) was associated with a greater number of cells exhibiting oscillations (26 ± 2.9 to 72 ± 3.6 % of cells in a given field) and which occurred with an increasing frequency (0.1 ± 0.02 to 0.27 ± 0.03 Hz). The increase in number of cells exhibiting oscillations and increased frequency of oscillations, with increments in pressure, persisted following either nifedipine or adenosine. In contrast to arterioles exhibiting active myogenic constriction to increases in pressure, vessels exposed to nifedipine or adenosine responded largely passively. Thus, oscillations in Ca2+i are not dependent on active myogenic constriction but are influenced by pressure‐induced distention.

Myogenic tone and reactivity of cerebral arteries in Type II diabetic BBZDR/Wor rat

BBZDR/Wor rat is a new model of type II diabetes with spontaneous obesity and clinical characteristics close to human diabetes. In this study the time-course of cerebroarterial dysfunction was characterized. Posterior cerebral arteries from BBZDR/Wor rats and their age-matched lean controls were pressurized to 70 mm Hg in an arteriograph. Effects of intraluminal pressure and different pharmacological agents on myogenic tone were evaluated. Pressure-myogenic tone curves in diabetic arteries were similar to that in non-diabetic arteries at pre-diabetic age, showed leftward shift at 4 weeks and were significantly different with higher myogenic tone at 5 and 8 months of diabetes. Age-dependent decrease in myogenic tone was observed in non-diabetic arteries. Dilation to histamine was similar to that in non-diabetic arteries at pre-diabetic and at 4 weeks but significantly reduced at 5 and 8 months of diabetes. Bradykinin-mediated dilation was significantly reduced in early and chronic diabetes, whereas (±)- S-nitroso- N-acetylpenicillamine (SNAP)-mediated dilation was decreased modestly at 8 months of diabetes. Sensitivity and constriction to 5-hydroxytryptamine were increased in early and chronic diabetes. Responses to bradykinin and 5-hydroxytryptamine were decreased and increased, respectively. Myogenic tone was significantly less sensitive to (lower pIC 50) U-73122 than normal arteries at 4 weeks and 8 months of diabetes suggesting an increased activation of phospholipase C (PLC). This study shows that pressure-mediated autoregulation of cerebral arteries in type II diabetes operates at higher resistance. Endothelium-dependent dilation was decreased with chronic diabetes with increased sensitivity to constrictor agonist. Endothelium-independent dilation was modestly affected. Arterial hyper-reactivity to pressure and constrictor agonist were likely due to increased PLC activation.

Myogenic tone and reactivity of the rat ophthalmic artery.

To study and quantify myogenic behavior and reactivity of the rat ophthalmic artery to pressure and different vasoactive substances in vitro. Rat ophthalmic arteries (diameter of 217 +/- 6 microm, n = 22) were isolated, cannulated with glass pipettes in an arteriograph and pressurized in a physiological buffer. Internal diameter was continuously monitored. The effect of intraluminal pressure on the diameter was assessed and concentration-response curves to different constrictor and dilator agonists were obtained at an intraluminal pressure of 70 mm Hg. Myogenic tone developed at an intraluminal pressure of 30 to 40 mm Hg, continued to increase, and was maintained up to a pressure of 199 mm Hg in these arteries. Arteries dilated and constricted in response to 16 and 60 mM potassium, respectively. Endothelin-1 was the most potent and efficacious constrictor, with a biphasic concentration-response curve, followed by vasopressin, serotonin, U-46619 and phenylephrine. Carbachol was the most efficacious dilator, followed by isoprenaline. The peptide dilators calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) were potent but less efficacious than carbachol and isoprenaline. Histamine and adenosine were even less potent and less efficacious dilators. NG-nitro-L-arginine methyl ester (L-NAME) constricted and indomethacin dilated the arteries. This study provides the first direct evidence for myogenic autoregulatory properties and pharmacological heterogeneity in the rat ophthalmic artery.

Pressure stimulates proliferation and DNA synthesis in rat intestinal epithelial cells

Effects of intraluminal pressure on cultured intestinal epithelial cells were assessed by measuring cell proliferation and DNA synthesis after exposure to various pressures. Pressures of 40 to 120 mm Hg promoted cell proliferation and DNA synthesis. Pressure-induced DNA synthesis was further enhanced by the addition of interleukin-2, suggesting the regulation of intestinal epithelial growth by pressure in coordination with cytokines. Pretreatment with either a phospholipase C inhibitor or protein kinase C inhibitor significantly inhibited DNA synthesis promoted by pressure and interleukin-2. This study demonstrates a novel mechanism whereby pressure regulates cell growth in intestinal epithelial cells, possibly via activation of phospholipase C and protein kinase C.

Lack of effect of intraluminal pressure on renin release from isolated afferent arterioles.

To evaluate the role of the proposed baroreceptor mechanism in the afferent arteriole in regulating renin release, we modified the isolated perfused tubule technique to perfuse afferent arterioles. Arterioles with attached glomeruli were isolated from rabbit kidneys and perfused using standard methods. To stop the arteriolar flow and allow perfusion pressure, as set by a mercury manometer, to be built up in the lumen of the vessel, the glomerulus was sucked into a constriction pipette. The preparation was continuously superfused with Krebs-Ringer solution in the first series of experiment, and a cell culture medium in the second series of experiment. The superfusate droplets were collected under mineral oil with 10-min collection intervals. The renin content of the samples was assayed by radioimmunoassay of the angiotensin I generated. In the two series of experiments we tested the effects of sequential changes in intraluminal pressure on renin release. In the first series of experiments (n = 6) the renin release was 56.3 nGU arteriole-1 min-1 in the first 10 min of sampling. The renin release was then constant for 80 min with an average of 21.6 nGU arteriole-1 min-1. In the last 30 min the renin release was 96.5 nGU arteriole-1 min-1. In the second series of experiments (n = 8) the renin release was 26.5 nGU arteriole-1 min-1 throughout the course of the experiment. These results indicate that under these conditions there is no relation between renin release and intraluminal pressure in afferent arterioles.

Hemodynamics During Increased Intraluminal Pressure in the Ileum of Suckling Swine

Studies of intestinal hemodynamics during increased abdominal and intraluminal pressure in adult animals (canine and feline) have shown that blood flow is practically unchanged at pressures up to 35-40 mm Hg. In the young animal, however, decreased total intestinal blood flow has been shown at pressures of 15 mm Hg or greater. To help characterize the effect of intraluminal pressure on intestinal circulation, we have studied pressure-flow relationships in an isolated loop of terminal ileum in piglets 2-14 days of age (mean, 6.1 +/- 3.7 SD, n = 14) with a mean weight of 1,745 +/- 345 SD. Intraluminal pressure was increased from 0-50 cm of water pressure in 10-cm steps of two min' duration. Blood flow was reduced with every increase in intraluminal pressure and significantly reduced at pressures of 20 cm of water or more. The calculated peripheral vascular resistance increased with every increment of intraluminal pressure. Analysis of the relationship of arterial blood pressure to changes in blood flow suggests that blood flow reductions are greater in animals with lower blood pressure at every level of intraluminal pressure studied. Increased intraluminal pressure could be a mechanism of intestinal mucosal ischemia in the newborn, particularly affecting those with low arterial blood pressure.

Segmental effects of norepinephrine and angiotensin II on isolated renal microvessels.

Interlobular arteries and superficial afferent and efferent arterioles were isolated from rabbit kidney, and the effects of intraluminal pressure, norepinephrine (NE), and angiotensin II (ANG II) on lumen diameter were examined. A single microvessel was dissected and one end was cannulated. The other end of the vessel was occluded and lumen diameter was measured at fixed intraluminal pressures. With step increases in intraluminal pressure over the range of 70-180 mmHg, lumen diameters of the interlobular arteries and afferent arterioles remained constant or decreased by up to 11%. In contrast, lumen diameters of efferent arterioles continued to increase as intraluminal pressure was elevated. In all three vessels NE (10(-9) to 10(-5) M) caused a dose-dependent decrease in lumen diameter. However, only the efferent arteriole responded to ANG II (10(-12) to 10(-8) M). The contractile response of the efferent arteriole to NE or ANG II was localized to the first 50-75 micrometers of the vessel as it emerged from the glomerulus. This finding suggests that smooth muscle cells are located only in this portion of the efferent arteriole. It is concluded that at least part of the autoregulation of renal blood flow can be explained by a myogenic mechanism in preglomerular vessels and that ANG II acts primarily on postglomerular segments of the rabbit renal microcirculation.

Effects of intraluminal pressure on regional blood flow in obstructed and unobstructed small intestines in the rat

Small bowel circulation in the rat was studied with the microsphere technique before and after 10 minutes of elevated intraintestinal pressure. A distal small bowel loop consisting of 10 vascular arcades was used. The specimens were inflated with nitrogen gas. Regional blood flow in both obstructed and unobstructed small bowels was significantly diminished by an intraintestinal pressure of 40 mm Hg. A pressure of 20 mm Hg impaired circulation only in the obstructed small intestine, whereas the unobstructed intestine did not show a similar decrease. These findings suggest that moderate intraluminal pressures can imply a potential hazard to the vulnerable capillary bed of an obstructed intestine. Hence, it is suggested that intraoperative decompression should be performed to avoid this postoperative threat to bowel viability.

Effect of intraluminal pressure on the ultrastructure and protein transport in the proximal tubule

Proteins filtered in the kidney are generally considered to be catabolized by the renal lysosomes, but it has also been suggested that some protein may pass the tubule wall intact via the intercellular spaces. To examine the latter possibility, electron-dense tracers were in one part of the study injected retrograde into the kidney of living flounders and in another part by micropuncture directly into the tubule lumen of isolated flounder kidney tubules incubated in vitro. In both cases disruptions in the tubule wall were demonstrated and this was shown to be associated with the passage of tracer into the lateral intercellular spaces. From the in vitro studies it was further shown that only when the intraluminal pressure is increased do tracers pass into the intercellular spaces and they do so via the disruptions in the tubule wall. It is concluded that no passage of tracer occurs at intraluminal pressures in the physiological range.

Effects of intraluminal pressure in the colon on its vascular pressure-flow relationships.

Distension of the small intestine has been shown to result in increased intraluminal pressure and resistance of blood flow (1). Welsh (2) concluded that mucosal blood flow in the colon is increased during periods of increased motility. Other studies showed that total colon blood flow is decreased during rhythmic contraction and by distension of the colon (3). Arterial pressure-flow studies have given evidence of autoregulation of blood flow in the small intestine (4) and colon (5). Elevation of venous pressure results in increased resistance in the intestine and the responses are abolished by the infusion of papaverine (5, 6). In the present paper data are given on the effects of distension of the colon on these vascular responses to changes in arterial or venous pressure.Methods.Dogs weighing 20-25 kg were anesthetized with pentobarbital (30 mg/kg, iv). The colon was exposed and freed of its mesenteric attachments. Heparin (500 units/kg, iv) was given. Then a second dog to serve as a perfusion donor was ...