Endothelium-dependent, flow-induced dilation of isolated coronary arterioles

1990 ◽  
Vol 259 (4) ◽  
pp. H1063-H1070 ◽  
Author(s):  
L. Kuo ◽  
M. J. Davis ◽  
W. M. Chilian
Keyword(s):  
Intraluminal Pressure ◽  
Flow Mediated Dilation ◽  
Mechanical Removal ◽  
Reservoir Systems ◽  
Spontaneous Tone ◽  
The Mean ◽  
Myogenic Responses ◽  
Dependent Flow ◽  
Coronary Arterioles

Flow-mediated dilation has been documented in large conduit coronary arteries but not in coronary arterioles. The goal of this study was to determine whether this response occurs in coronary arterioles and whether it competes with myogenic constriction. Subepicardial arterioles (40-80 microns) were isolated and cannulated with two glass micropipettes connected to independent reservoir systems. During zero flow, myogenic responses were studied over the range of intraluminal pressure (IP) between 20 and 140 cmH2O. Myogenic constrictions and dilations was observed when IP was increased (greater than 60 cmH2O) and decreased (less than 60 cmH2O), respectively. Flow was initiated by simultaneously moving the reservoirs in equal and opposite directions, thus generating a pressure gradient (delta P) without changing the mean luminal pressure (range delta P = 4-60 cmH2O). Flow-induced responses were studied at low, intermediate, and high myogenic tones by setting IP at 20, 60, and 100 cmH2O, respectively. The threshold for flow-induced dilation was delta P = 4 cmH2O, and maximum dilation was observed at delta P = 20 cmH2O. Red cell velocities in isolated arterioles at delta P of 4 and 60 cmH2O were 1.2 +/- 0.2 and 15.9 +/- 1.3 mm/s, respectively, which are within the range of those reported for coronary microvessels in vivo. The magnitude of the flow-induced dilation was greatest at the intermediate tone (60 cmH2O IP) but was attenuated at lower and higher IP. After mechanical removal of the endothelium, spontaneous tone and myogenic responses were preserved, but flow-induced dilation and bradykinin-induced dilation were abolished.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of pressure- and flow-induced responses in porcine coronary resistance vessels

1991 ◽  
Vol 261 (6) ◽  
pp. H1706-H1715 ◽  
Author(s):  
L. Kuo ◽  
W. M. Chilian ◽  
M. J. Davis
Keyword(s):  
Vascular Tone ◽  
Intraluminal Pressure ◽  
Myogenic Tone ◽  
Flow Mediated Dilation ◽  
Induced Responses ◽  
Coronary Resistance ◽  
Mechanical Removal ◽  
Resistance Vessels ◽  
Reservoir Systems ◽  
The Mean

Pressure-induced myogenic responses and flow-induced vasodilatory responses have been documented in coronary resistance arterioles, but the interaction of these two mechanisms and the nature of the flow-mediated response are not well understood. Experiments were designed to quantitatively study the interaction of pressure- and flow-induced responses and to characterize the nature of the substance responsible for flow-mediated dilation in isolated coronary arterioles. Subepicardial arterioles (40-80 microns) were isolated from pigs and cannulated with two glass micropipettes and then pressurized via independent reservoir systems. Flow was initiated by simultaneously moving the reservoirs in equal and opposite directions thus generating a pressure gradient (delta P) without changing the mean intraluminal pressure (IP). IP was changed by moving both reservoirs in the same direction to alter myogenic tone in the absence of flow (delta P = 0). Flow-mediated dilation competed with myogenic constriction when flow and pressure were elevated. Also, flow potentiated myogenic dilation when IP was decreased. The magnitude of flow-induced dilation was greatest at an intermediate level of vascular tone (IP = 60 cmH2O) but was attenuated at higher and lower levels of tone. In the presence of flow (delta P = 4 cmH2O), pressure-diameter relationships were shifted upward, and the magnitude of myogenic responsiveness was attenuated. Double-vessel bioassay studies indicated that a transferable substance was released from intact endothelium in response to flow. Flow-induced dilation was not affected by indomethacin but was abolished by NG-monomethyl-L-arginine or by mechanical removal of endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Endotoxin impairs flow-induced vasodilation of porcine coronary arterioles

1992 ◽  
Vol 262 (6) ◽  
pp. H1838-H1845 ◽  
Author(s):  
L. Kuo ◽  
W. M. Chilian ◽  
M. J. Davis ◽  
M. H. Laughlin
Keyword(s):  
Nitric Oxide ◽  
Intraluminal Pressure ◽  
In Vitro Incubation ◽  
Maximal Diameter ◽  
Endotoxin Exposure ◽  
Reservoir Systems ◽  
Spontaneous Tone ◽  
Nitric Oxide Pathway ◽  
Coronary Arterioles

The purpose of this study was to test the hypothesis that endotoxemia impairs endothelium-dependent (both receptor-mediated and flow-induced) vasodilation in porcine coronary arterioles. Coronary arterioles were isolated from three groups of 4- to 8-wk old (10.3 +/- 0.8 kg) pigs: endotoxemic (E; 250 micrograms/kg endotoxin iv), control (C; equal volume of saline), and untreated pigs (UT). Subepicardial arterioles (60-120 microns) were isolated and cannulated with two micropipettes that were connected to two independent reservoir systems. Intraluminal pressure was set at 60 cmH2O throughout the experiments. All C vessels developed spontaneous tone and exhibited flow-induced vasodilation from 65 to 95% maximal diameter. Spontaneous tone developed in only three of five arterioles from E pigs, and flow-induced vasodilation was not observed in any arteriole from E pigs. Spontaneous tone developed in all six arterioles isolated from UT pigs but disappeared in four of these vessels as a result of 1 h of in vitro incubation with endotoxin (2.5 micrograms/ml). Flow-induced vasodilation was also abolished in these vessels after 1 h of endotoxin exposure. Incubation with 3 mM L-arginine, in vitro, restored flow-induced vasodilation in E arterioles and endotoxin-treated UT arterioles. Vasoconstriction induced by acetylcholine (ACh) and vasodilation induced by nitroprusside (NP) and bradykinin (BK) were similar in arterioles from all groups. In contrast, endotoxin impairs flow-induced vasodilation of coronary arterioles. The mechanism responsible for the impairment of flow-induced vasodilation seems to reside in disruption of the L-arginine/nitric oxide pathway.

Myogenic activity in isolated subepicardial and subendocardial coronary arterioles

1988 ◽  
Vol 255 (6) ◽  
pp. H1558-H1562 ◽  
Author(s):  
L. Kuo ◽  
M. J. Davis ◽  
W. M. Chilian
Keyword(s):  
High Pressures ◽  
In Vitro Study ◽  
Intraluminal Pressure ◽  
Physiological Salt Solution ◽  
India Ink ◽  
Myogenic Activity ◽  
Myogenic Responses ◽  
Pressure Changes ◽  
Coronary Arterioles

The goal of this study was to examine myogenic responses of isolated porcine subepicardial and subendocardial arterioles (80–100 micron in diameter) within physiological ranges of intraluminal pressure. Arterioles were located by perfusion with india ink-gelatin solution then dissected and cannulated with glass micropipettes. Intraluminal pressure was altered in 20-cmH2O steps over the range of 20–140 cmH2O. IN physiological salt solution (36–37 degrees C), the coronary arterioles developed spontaneous tone and exhibited myogenic responses. At the lower pressures (20–60 cmH2O), subendocardial arterioles responded passively (diameter decreased from a control diameter at 60 cmH2O), whereas subepicardial arterioles maintained their diameters. At higher pressures (100–140 cmH2O), both subepicardial and subendocardial arterioles demonstrated myogenic constriction, but subepicardial arterioles demonstrated greater myogenic constriction than subendocardial arterioles. This implies that myogenic autoregulation in subepicardial arterioles is better than that in the subendocardial arterioles at both low and high pressures. In the presence of nitroprusside (10(-4) M), all arterioles responded to pressure changes passively, and there were no differences between subepicardial and subendocardial vessels. The functional integrity of the endothelium was verified by relaxation to substance P (10(-7) M). This is the first in vitro study to demonstrate coronary myogenic activity and transmural differences in these arteriolar responses. Our data support the concept that myogenic mechanisms in 80 to 100-micron arterioles may actively contribute to autoregulation of coronary blood flow.

Coronary arteriolar flow-induced vasodilation signals through tyrosine kinase

1996 ◽  
Vol 270 (6) ◽  
pp. H1878-H1884 ◽  
Author(s):  
J. M. Muller ◽  
M. J. Davis ◽  
W. M. Chilian
Keyword(s):  
Substance P ◽  
Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Kinase Inhibitors ◽  
Fluorescein Isothiocyanate ◽  
Intraluminal Pressure ◽  
Kinase Activation ◽  
Genistein Treatment ◽  
Dependent Flow ◽  
Coronary Arterioles

Coronary arterioles demonstrate flow-dependent vasodilation that is mediated by endothelial release of nitric oxide. The signaling mechanisms for this response remain unknown. Because tyrosine kinases are an enzyme family linked to many signaling pathways, including some for mechanosensitive transduction, we hypothesized that tyrosine kinase activation is a critical step in flow-induced vasodilation. To test this hypothesis, coronary arterioles were isolated, cannulated with micropipettes, and perfused by two independent reservoir systems. Intraluminal pressure was set at 60 cmH2O, and flow was generated by changing the heights of the reservoirs in equal and opposite directions, thus establishing a pressure difference across the arteriole without altering intraluminal pressure. Vasodilatory responses to intraluminal flow and substance P (1 x 10(-12) to 1 x 10(-7) M) were evaluated before and after intraluminal application of the tyrosine kinase inhibitors genistein (5 microM) and piceatannol (10 microM). Exposure to these inhibitors did not alter spontaneous tone. Substance P caused dose-dependent vasodilation that was not affected by genistein or piceatannol. Increases in intraluminal flow (generated by pressure differences ranging from 4 to 60 cmH2O) elicited graded increases in diameter. Both genistein and piceatannol inhibited the vasodilatory responses to flow. Treatment with daidzein, an inactive analogue of genistein, had no effect on either the flow-induced responses or substance P-induced vasodilation. To further confirm that tyrosine kinase activation is involved in flow-induced vasodilation, vessels were exposed to flow in the absence or presence of genistein and subsequently stained with a fluorescein isothiocyanate-labeled phosphotyrosine antibody. Exposure to flow significantly increased fluorescence of endothelial cells. Genistein treatment reversed the flow-induced increase in tyrosine phosphorylation. These results indicate that endothelium-dependent, flow-induced vasodilation in isolated porcine coronary arterioles is accompanied by an increase in tyrosine kinase activity. We conclude that endothelium-dependent, nitroxidergic, flow-induced vasodilation is mediated, at least in part, by a signaling pathway involving a tyrosine kinase.

Enhanced myogenic activation in skeletal muscle arterioles from spontaneously hypertensive rats

1993 ◽  
Vol 265 (6) ◽  
pp. H1847-H1855 ◽  
Author(s):  
J. C. Falcone ◽  
H. J. Granger ◽  
G. A. Meininger
Keyword(s):  
Venous Pressure ◽  
Muscle Length ◽  
Vascular Wall ◽  
Intraluminal Pressure ◽  
Active Tension ◽  
Hypertensive Rats ◽  
Cross Sectional ◽  
Wall Area ◽  
Myogenic Responses

The purpose of this study was to determine whether the vascular myogenic response is enhanced in hypertension. Experiments were conducted in the intact cremaster muscle microcirculation as well as in isolated arterioles of hypertensive (SHR) and normotensive (WKY) rats. Increasing venous pressure in vivo by approximately 5 mmHg had no effect on normotensive first- (1A) or third-order arteriolar (3A) diameters; in contrast, hypertensive 1A diameter decreased 4% (89 +/- 2 to 85 +/- 3 microns) with an 8% decrease in 3A (24 +/- 2 to 22 +/- 2 microns). To further examine this enhanced constriction to elevated intravascular pressure in SHR, diameter was monitored in isolated 1A during step increases and decreases in intraluminal pressure. Normotensive arterioles displayed myogenic responses between pressures of 50 and 170 cmH2O; in contrast, hypertensive arterioles demonstrated myogenic responses over an extended pressure range (50–210 cmH2O). In addition, the change in diameter for each step change in pressure was greater in the arterioles from SHR, indicating an increased myogenic responsiveness. The myogenic reactions were unaffected by alpha-receptor blockade with phentolamine (10(-6) M), indicating that adrenergic hypersensitivity was not involved in the enhanced response to stretch. Morphometric analysis of the vascular wall revealed no differences in wall thickness, cross-sectional wall area, or wall-to-lumen ratio between normotensive and hypertensive rats. The length-tension relationships for normotensive and hypertensive rats demonstrated that peak active tension occurred at nearly the same vascular smooth muscle length. In addition, SHR arterioles were capable of maintaining higher levels of active tension that WKY arterioles, indicating an altered length-tension curve in chronic arterial hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Age-associated impairment in vasorelaxation to fluid shear stress in the female vasculature is improved by TNF-α antagonism

2006 ◽  
Vol 290 (3) ◽  
pp. H1259-H1263 ◽  
Author(s):  
Ivan A. Arenas ◽  
Yi Xu ◽  
Sandra T. Davidge
Keyword(s):  
Shear Stress ◽  
Methyl Ester ◽  
Fluid Shear Stress ◽  
Mesenteric Arteries ◽  
Female Rats ◽  
Intraluminal Pressure ◽  
Flow Mediated Dilation ◽  
Sprague Dawley ◽  
Tnf Α

Aging is associated with alterations in vascular homeostasis, including a reduction in flow-mediated vasodilation, which in women is related to the onset of menopause. We previously found that in female animals, aging is associated with an increase in TNF-α. Thus we investigated the role of in vivo TNF-α inhibition on vascular responses to shear stress in aging female rats. Mesenteric arteries (∼150 μm) were isolated from young (3 mo) and ovariectomized Sprague-Dawley female rats approaching reproductive senescence (12 mo) treated with either placebo or a TNF-α inhibitor (etanercept; 0.3 mg/kg) and were mounted on a pressure myograph system. Vessels were equilibrated at an intraluminal pressure of 60 mmHg and then preconstricted with phenylephrine at ∼70% of their initial diameter. Perfusate flow was increased in steps from 0 to 150 μl/min. Compared with young vessels, aged vessels have a decrease in flow-mediated dilation [maximal dilation (means ± SE): 52 ± 4 vs. 24 ± 15%; P < 0.05], which was improved by TNF-α inhibition. Moreover, in aged vessels maximal dilation to flow was achieved at higher levels of shear stress compared with young vessels. In all groups, flow-mediated dilation was abolished by either endothelial removal or nitric oxide synthase inhibition with NG-nitro-l-arginine methyl ester. However, the modulation by NG-nitro-l-arginine methyl ester was reduced in vessels from aged animals compared with young animals but was improved in the etanercept-treated aged animals. In vivo chronic TNF-α inhibition improves flow-mediated arterial dilation in resistance arteries of aged female animals.

Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

1996 ◽  
Vol 76 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Yasuto Sasaki ◽  
Junji Seki ◽  
John C Giddings ◽  
Junichiro Yamamoto
Keyword(s):  
Blood Flow ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Red Cell ◽  
Cell Velocity ◽  
Red Cell Velocity ◽  
The Mean ◽  
Wall Shear ◽  
Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

Influence of Platelet Membrane Sialic Acid and Platelet-Associated IgG on Ageing and Sequestration of Blood Platelets in Baboons

1993 ◽  
Vol 70 (04) ◽  
pp. 676-680 ◽  
Author(s):  
H F Kotzé ◽  
V van Wyk ◽  
P N Badenhorst ◽  
A du P Heyns ◽  
J P Roodt ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Life Span ◽  
Blood Platelets ◽  
Senescent Cell ◽  
Platelet Membrane ◽  
Antigen Complex ◽  
The Mean ◽  
Aggregation Of Platelets

SummaryPlatelets were isolated from blood of baboons and treated with neuraminidase to remove platelet membrane sialic acid, a process which artificially ages the platelets. The platelets were then labelled with 111In and their mean life span, in vivo distribution and sites of Sequestration were measured. The effect of removal of sialic acid on the attachment of immunoglobulin to platelets were investigated and related to the Sequestration of the platelets by the spleen, liver, and bone marrow. Removal of sialic acid by neuraminidase did not affect the aggregation of platelets by agonists in vitro, nor their sites of Sequestration. The removal of 0.51 (median, range 0.01 to 2.10) nmol sialic acid/108 platelets shortened their life span by 75 h (median, range 0 to 132) h (n = 19, p <0.001), and there was an exponential correlation between the shortening of the mean platelet life span and the amount of sialic acid removed. The increase in platelet-associated IgG was 0.112 (median, range 0.007 to 0.309) fg/platelet (n = 25, p <0.001) after 0.79 (median, range 0.00 to 6.70) nmol sialic acid/108 platelets was removed (p <0.001). There was an exponential correlation between the shortening of mean platelet life span after the removal of sialic acid and the increase in platelet-associated IgG. The results suggest that platelet membrane sialic acid influences ageing of circulating platelets, and that the loss of sialic acid may have exposed a senescent cell antigen that binds IgG on the platelet membrane. The antibody-antigen complex may then provide a signal to the macrophages that the platelet is old, and can be phagocytosed and destroyed.

scholarly journals Formulation and in vitro evaluation of self-nanoemulsifying liquisolid tablets of furosemide

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lena Dalal ◽  
Abdul Wahab Allaf ◽  
Hind El-Zein
Keyword(s):  
Theoretical Model ◽  
Castor Oil ◽  
In Vivo Studies ◽  
Coating Materials ◽  
Peg 400 ◽  
The Mean ◽  
Usp Apparatus ◽  
Solid System

AbstractSelf-nanoemulsifying drug delivery systems (SNEDDS) were used to enhance the dissolution rate of furosemide as a model for class IV drugs and the system was solidified into liquisolid tablets. SNEDDS of furosemide contained 10% Castor oil, 60% Cremophor EL, and 30% PEG 400. The mean droplets size was 17.9 ± 4.5 nm. The theoretical model was used to calculate the amounts of the carrier (Avicel PH101) and coating materials (Aerosil 200) to prepare liquisolid powder. Carrier/coating materials ratio of 5/1 was used and Ludipress was added to the solid system, thus tablets with hardness of 45 ± 2 N were obtained. Liquisolid tablets showed 2-folds increase in drug release as compared to the generic tablets after 60 min in HCl 0.1 N using USP apparatus-II. Furosemide loaded SNEDDS tablets have great prospects for further in vivo studies, and the theoretical model is useful for calculating the adequate amounts of adsorbents required to solidify these systems.

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