Vasomotion Amplitude Research Articles

Skin microcirculation in middle-aged men with newly diagnosed arterial hypertension according to remote laser Doppler flowmetry data.

This work aims to study the functional state of resistive skin microvessels in patients with newly diagnosed arterial hypertension (AH), using portable laser Doppler flowmetry (LDF) devices. The study included 89 men aged 30 to 60 years (44.4 ± 8.5) who had no known medical complaints, subjectively considered themselves healthy, and did not take medications on a regular basis. All the men underwent LDF on the left forearm, daily blood pressure (BP) monitoring (DBPM) on the left arm, echocardiography, and laboratory tests. According to DBPM data, the men were divided into two groups. The control group (CG) consisted of 30 men with normal BP, and 59 men were included in the AH group. According to LDF data, in men with AH, there is a decrease in the amplitude (tone increase) of neurogenic and myogenic vasomotion, a decrease in the amplitude of pulse oscillations of microcirculatory flow, a decrease in perfusion efficiency of endothelial, neurogenic, myogenic and pulse mechanisms of tissue perfusion regulation. Of all tone-forming mechanisms, only the myogenic mechanism has a weak negative correlation with systolic blood pressure level. The amplitude of pulse oscillations demonstrates the highest degree of correlation with blood pressure parameters. The functional disorders of vasomotor activity of resistive skin microvessels revealed in men with AH have minor correlations with the level of blood pressure. Despite this, the use of portable devices for remote LDF may be a useful method for the dynamic monitoring of patients with hypertension, which requires further research. • In early arterial hypertension (AH) perfusion efficiency in skin is reduced. • Neurogenic and myogenic vasomotor tones increase with the development of AH. • Pulse oscillations demonstrate the highest correlation with blood pressure. • Wrist-mounted LDF monitors are promising for early hypertension monitoring.

Pancreatic Microcirculation Profiles in the Progression of Hypertension in Spontaneously Hypertensive Rats.

BACKGROUNDEmerging evidence indicates that the pancreas serves as a major source of degrading protease activities and that uncontrolled proteolytic receptor cleavage occurs under hypertensive conditions, which leading to systemic dysfunction and end-organic damage. However, changes in pancreatic microcirculation profiles during the progression of hypertension remain unknown.METHODSPancreatic microcirculatory blood distribution patterns and microvascular vasomotion of spontaneously hypertensive rats (SHRs) and normotensive control Wistar Kyoto rats at 5, 8, 13, and 18 weeks of age were determined. Wavelet transform analysis was performed to convert pancreatic microhemodynamic signals into time–frequency domains and construct 3-dimensional spectral scalograms. The amplitudes of characteristic oscillators including endothelial, neurogenic, myogenic, respiratory, and cardiac oscillators were compared among groups. Plasma nitrite/nitrate levels were measured using a Griess reaction. Additionally, endothelin-1, malondialdehyde, superoxide dismutase, and interleukin-6 levels were determined by enzyme-linked immunosorbent assay.RESULTSSHRs exhibited a reduced blood distribution pattern with progressively decreased average blood perfusion, amplitude, and frequency of microvascular vasomotion. Wavelet transform spectral analysis revealed significantly reduced amplitudes of endothelial oscillators from 8- to 18-week-old SHRs. Additionally, the blood microcirculatory chemistry complements explained the microhemodynamic profiles partially, as demonstrated by an increase in plasma nitrite/nitrate, endothelin-1, malondialdehyde, and interleukin-6 levels and a decreased superoxide dismutase level in SHRs.CONCLUSIONSPancreatic microcirculation profiles are abnormal in the progression of hypertension in SHRs, including a disarranged blood distribution pattern, impaired microvascular vasomotion, and reduced amplitudes of endothelial oscillators.

Angiotensin-(1-7) Treatment Restores Pancreatic Microcirculation Profiles: A New Story in Acute Pancreatitis.

The aim of this study was to investigate the changes of pancreatic microvascular vasomotion and blood distribution pattern in acute pancreatitis (AP), and whether Angiotensin (Ang)-(1-7) treatment could restore pancreatic microcirculation profiles. Mice were randomly separated into control, AP, and Ang-(1-7)-treated AP (A-AP) group. Acute pancreatitis was induced in mice by intraperitoneal injection of cerulein and lipopolysaccharide. Pancreatitis was confirmed by histopathology, serum amylase, and high-sensitive C-reactive protein. Pancreatic microvascular vasomotion and blood distribution pattern in AP progression were assessed by laser Doppler. Meanwhile, ultrastructural changes of pancreatic microcirculation, including microvascular cavity and wall and endothelial mitochondria, were evaluated by transmission electron microscopy. Acute pancreatitis mice exhibited pathological pancreatic injuries with lower blood distribution pattern and decreased average blood perfusion, relative velocity, effective frequency, and amplitude of microvascular vasomotion. The pancreatic pathological injuries in Ang-(1-7)-treated mice were significantly alleviated. Consistently, Ang-(1-7) treatment led to a restoration in pancreatic microcirculation profiles. Furthermore, non-Ang-(1-7)-treated mice showed an irregular microvascular wall, narrow cavity, and swelling mitochondria, and these ultrastructural impairments were reversed by Ang-(1-7) administration. Pancreatic microcirculation profiles are abnormal in the progression of AP. Angiotensin-(1-7) administration could restore functional status of pancreatic microcirculation.

Vasomotion as a Driving Force for Paravascular Clearance in the Awake Mouse Brain

Paravascular drainage of solutes, including β-amyloid (Aβ), appears to be an important process in brainhealth and diseases such as Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). However, the major driving force for clearance remains largely unknown. Here we used invivo two-photon microscopy in awake head-fixed mice to assess the role of spontaneous vasomotion in paravascular clearance. Vasomotion correlated with paravascular clearance of fluorescent dextran from the interstitial fluid. Increasing the amplitude of vasomotion by means of visually evoked vascular responses resulted in increased clearance rates in the visual cortex of awake mice. Evoked vascular reactivity was impaired in mice with CAA, which corresponded to slower clearance rates. Our findings suggest that low-frequency arteriolar oscillations drive drainage of solutes. Targeting naturally occurring vasomotion in patients with CAA or AD may be a promising early therapeutic option for prevention of Aβ accumulation in the brain.

Pancreatic-islet microvascular vasomotion dysfunction in mice with spinal cord injury

Patients with spinal cord injury (SCI) have an increased risk for developing type 2 diabetes. It is unknown whether the pancreatic-islet microvascular vasomotion is involved. We used female C57BL/6 mice and a 100-kilodyne T10 Infinite Horizons contusion SCI (or T10 laminectomy) to detect blood glucose and pancreatic-islet microvascular vasomotion. Blood glucose obtained from tail vein was detected using one Touch UltraEasy glucometer. Glucose tolerance test was performed by d-glucose administration intraperitoneally. Functional status of pancreatic-islet microvascular vasomotion was determined by laser Doppler monitoring. Expressions of insulin and glucagon were determined by immunohistochemistry. Expression of VEGF-A was determined by immunohistochemistry and Western blotting. Our result demonstrated that blood glucose was significantly increased at 4 h postinjury compared to that in sham group, with continuous higher blood glucose until 4 days postinjury (p < 0.05). SCI mice at day 7 and day 14 had significantly impaired glucose tolerance following glucose administration (p < 0.01). Average blood perfusion, amplitude, frequency, and relative velocity of vasomotion were significantly lower at 6 h postinjury than those in the sham group (p < 0.05), which were gradually upregulated over time. The expression of insulin was decreased, while the expression of glucagon was increased at 6 h postinjury. Similarly, the expression of VEGF-A was significantly decreased at 6 h postinjury, compared to that in sham group (p < 0.05), with slight increases by 14 days postinjury. Our study suggests that the functional status of pancreatic-islet microvascular vasomotion is impaired after injury, which may have implications for developing effective therapeutic interventions for SCI.

Increase in slow-wave vasomotion by hypoxia and ischemia in lowlanders and highlanders.

The physiological relevance of slow-wave vasomotion is still unclear, even though it has been hypothesized that it could be a compensatory mechanism for enhancing tissue oxygenation in conditions of reduced oxygen supply. The aim of our study was to explore the effects of hypoxia and ischemia on slow-wave vasomotion in microcirculation. Peripheral oxygen saturation and forearm microcirculation flow (laser-Doppler flowmetry) were recorded at baseline and during postocclusive reactive hyperemia in the Himalaya region from 8 European lowlanders (6 men; aged 29-39 yr) at 1,350, 3,400, and 5,050 m and from 10 Nepalese male highlanders (aged 21-39 yr) at 3,400 and 5,050 m of altitude. The same measurements were also performed at sea level in 16 healthy volunteers (aged 23-61 yr) during a short-term exposure to normobaric hypoxia. In lowlanders, exposure to progressively higher altitude under baseline flow conditions progressively increased 0.06-0.15 Hz vasomotion amplitude [power spectral density % was expressed as geometric means (geometric standard deviation) = 14.0 (3.6) at 1,350 m; 87.0(2.3) at 3,400 m and 249.8 (3.6) at 5,050 m; P = 0.006 and P < 0.001 vs. 1,350 m, respectively]. In highlanders, low frequency vasomotion amplitude was similarly enhanced at different altitudes [power spectral density % = 183.4 (4.1) at 3,400 m vs. 236.0 (3.0) at 5,050 m; P = 0.139]. In both groups at altitude, it was further increased after ischemic stimulus ( P < 0.001). At baseline, acute short lasting normobaric hypoxia did not induce low frequency vasomotion, which was conversely induced by ischemia, even under normal oxygenation and barometric pressure. This study offers the demonstration of a significant increase in slow-wave vasomotion under prolonged hypobaric-hypoxia exposure at high altitude, with a further enhancement after ischemia induction. NEW & NOTEWORTHY This study offers the demonstration in humans of the occurrence of enhanced slow-wave vasomotion in microcirculation induced by exposure to hypobaric hypoxia, ischemia, and their combination. This phenomenon, where vasomotion can be hypothesized to behave as a "peripheral heart," may represent a compensating adaptive change aimed at improving peripheral flow and tissue oxygenation in conditions of reduced oxygen supply, such as altitude-induced hypobaric hypoxia and postocclusion ischemia.

Laser Doppler: A Tool for Measuring Pancreatic Islet Microvascular Vasomotion &lt;em&gt;In Vivo&lt;/em&gt;

As a functional status of microcirculation, microvascular vasomotion is important for the delivery of oxygen and nutrients and the removal of carbon dioxide and waste products. The impairment of microvascular vasomotion might be a crucial step in the development of microcirculation-related diseases. In addition, the highly vascularized pancreatic islet is adapted to support endocrine function. In this respect, it seems possible to infer that the functional status of pancreatic islet microvascular vasomotion might affect pancreatic islet function. Analyzing the pathological changes of the functional status of pancreatic islet microvascular vasomotion may be a feasible strategy to determine contributions that pancreatic islet microcirculation makes to related diseases, such as diabetes mellitus, pancreatitis, etc. Therefore, this protocol describes using a laser Doppler blood flow monitor to determine the functional status of pancreatic islet microvascular vasomotion, and to establish parameters (including average blood perfusion, amplitude, frequency, and relative velocity of pancreatic islet microvascular vasomotion) for evaluation of the microcirculatory functional status. In a streptozotocin-induced diabetic mouse model, we observed an impaired functional status of pancreatic islet microvascular vasomotion. In conclusion, this approach for assessing pancreatic islet microvascular vasomotion in vivo may reveal mechanisms relating to pancreatic islet diseases.

Laser Doppler: A Tool for Measuring Pancreatic Islet Microvascular Vasomotion In Vivo.

As a functional status of microcirculation, microvascular vasomotion is important for the delivery of oxygen and nutrients and the removal of carbon dioxide and waste products. The impairment of microvascular vasomotion might be a crucial step in the development of microcirculation-related diseases. In addition, the highly vascularized pancreatic islet is adapted to support endocrine function. In this respect, it seems possible to infer that the functional status of pancreatic islet microvascular vasomotion might affect pancreatic islet function. Analyzing the pathological changes of the functional status of pancreatic islet microvascular vasomotion may be a feasible strategy to determine contributions that pancreatic islet microcirculation makes to related diseases, such as diabetes mellitus, pancreatitis, etc. Therefore, this protocol describes using a laser Doppler blood flow monitor to determine the functional status of pancreatic islet microvascular vasomotion, and to establish parameters (including average blood perfusion, amplitude, frequency, and relative velocity of pancreatic islet microvascular vasomotion) for evaluation of the microcirculatory functional status. In a streptozotocin-induced diabetic mouse model, we observed an impaired functional status of pancreatic islet microvascular vasomotion. In conclusion, this approach for assessing pancreatic islet microvascular vasomotion in vivo may reveal mechanisms relating to pancreatic islet diseases.

Insulin treatment restores islet microvascular vasomotion function in diabetic mice.

The microcirculation plays an important role in the pathogenesis of diabetes and its complications. We hypothesized that pancreatic islet microvascular (PIM) vasomotion, as a parameter of pancreatic islet microcirculation function, is abnormal in diabetic mice and that insulin treatment may reverse this dysfunction. Mice were randomly assigned to non-diabetic control, untreated diabetic, and insulin-treated diabetic groups (n = 6 in each group). Separate groups of streptozotocin (STZ)-induced diabetic and high-fat diet-fed mice were used as a model of hyperglycemia. Insulin-treated diabetic mice were treated with 1-1.5 IU/day insulin for 1 week. Laser Doppler monitors were used to evaluate PIM vasomotion. Morphological and ultrastructural changes in islet endothelial cells were determined by immunohistochemistry and transmission electron microscopy. Glucagon, insulin, vascular endothelial growth factor (VEGF)-A, and platelet endothelial cell adhesion molecule (PECAM-1) expression was determined by immunohistochemistry and Western blotting. In both untreated diabetic groups, the pancreatic islet microcirculation was unable to regulate PIM vasomotion. The rhythm of vasomotion was irregular, and the average blood perfusion, amplitude, frequency, and relative velocity of vasomotion were significantly lower than in non-diabetic controls. Insulin treatment restored the functional status of PIM vasomotion. In islet endothelial cells from both untreated diabetic groups, the mitochondria were swollen with disarrangement of the cristae, and the distribution of PECAM-1 was discontinuous. Insulin treatment significantly increased the reduced expression of PECAM-1 in both untreated diabetic groups and VEGF-A expression in untreated STZ-diabetic mice. The results suggest that the functional status of PIM vasomotion is impaired in diabetic mice but can be restored by insulin.

Na-K-ATPase regulates intercellular communication in the vascular wall via cSrc kinase-dependent connexin43 phosphorylation.

Communication between vascular smooth muscle cells (VSMCs) is dependent on gap junctions and is regulated by the Na-K-ATPase. The Na-K-ATPase is therefore important for synchronized VSMC oscillatory activity, i.e., vasomotion. The signaling between the Na-K-ATPase and gap junctions is unknown. We tested here the hypothesis that this signaling involves cSrc kinase. Intercellular communication was assessed by membrane capacitance measurements of electrically coupled VSMCs. Vasomotion in isometric myograph, input resistance, and synchronized [Ca2+]i transients were used as readout for intercellular coupling in rat mesenteric small arteries in vitro. Phosphorylation of cSrc kinase and connexin43 (Cx43) were semiquantified by Western blotting. Micromole concentration of ouabain reduced the amplitude of norepinephrine-induced vasomotion and desynchronized Ca2+ transients in VSMC in the arterial wall. Ouabain also increased input resistance in the arterial wall. These effects of ouabain were antagonized by inhibition of tyrosine phosphorylation with genistein, PP2, and by an inhibitor of the Na-K-ATPase-dependent cSrc activation, pNaKtide. Moreover, inhibition of cSrc phosphorylation increased vasomotion amplitude and decreased the resistance between cells in the vascular wall. Ouabain inhibited the electrical coupling between A7r5 cells, but pNaKtide restored the electrical coupling. Ouabain increased cSrc autophosphorylation of tyrosine 418 (Y418) required for full catalytic activity whereas pNaKtide antagonized it. This cSrc activation was associated with Cx43 phosphorylation of tyrosine 265 (Y265). Our findings demonstrate that Na-K-ATPase regulates intercellular communication in the vascular wall via cSrc-dependent Cx43 tyrosine phosphorylation.

Static Magnetic Field Effects on Impaired Peripheral Vasomotion in Conscious Rats

We investigated the SMF effects on hemodynamics in the caudal artery-ligated rat as an in vivo ischemia model using noninvasive near-infrared spectroscopy (NIRS) combined with power spectral analysis by fast Fourier transform. Male Wistar rats in the growth stage (10 weeks old) were randomly assigned into four groups: (i) intact and nonoperated cage control (n = 20); (ii) ligated alone (n = 20); (iii) ligated and implanted with a nonmagnetized rod (sham magnet; n = 22); and (vi) ligated and implanted with a magnetized rod (n = 22). After caudal artery ligation, a magnetized or unmagnetized rod (maximum magnetic flux density of 160 mT) was implanted transcortically into the middle diaphysis of the fifth caudal vertebra. During the experimental period of 7 weeks, NIRS measurements were performed in 3- , 5- , and 7-week sessions and the vasomotion amplitude and frequency were analyzed by fast Fourier transform. Exposure for 3–7 weeks to the SMF significantly contracted the increased vasomotion amplitude in the ischemic area. These results suggest that SMF may have a regulatory effect on rhythmic vasomotion in the ischemic area by smoothing the vasomotion amplitude in the early stage of the wound healing process.

108 THE FUNCTIONAL ROLE OF CA2+-ACTIVATED CL- CHANNEL CANDIDATES IN VASCULAR SMOOTH MUSCLE CELLS

The Ca2+-activated Cl- conductance in the vascular smooth muscle cells (VSMCs) is well characterized but its molecular origin is under debate. The members of TMEM16 and Bestrophin families are potent candidates for the Ca2+-activated Cl- channel-forming protein. We have previously characterized in the VSMCs two Ca2+-activated Cl- currents (ICl(Ca)) with distinct characteristics and suggested that at least one of these currents is important for synchronized rhythmic contraction in the arterial wall, vasomotion. We tested here an association of TMEM16A and Bestrophins with ICl(Ca) and an importance of these proteins for VSMCs synchronization in the vascular wall. We downregulated TMEM16A and Bestrophin-3 using in vivo siRNA transfection of rat mesenteric small arteries. Knockdown was confirmed at mRNA and protein levels. The ICl(Ca) were analysed by patch clamp and arteries were tested functionally in isometric myograph. Downregulation of Bestrophin-3 induced secondary reduction in Bestrophin-1 and -2 expressions. VSMCs downregulated for Bestrophins had significantly reduced the cGMP-dependent ICl(Ca). Bestrophins downregulation was without effect on contractile responses. In contrast, TMEM16A downregulation abolished both types of the ICl(Ca). Arteries downregulated for TMEM16A had suppressed contractility to agonist (noradrenaline and vasopressin) stimulation and high extracellular K+ solution. The amplitude of vasomotion was significantly reduced after both TMEM16A and Bestrophins downregulation. We conclude that both Bestrophins and TMEM16A are associated with the cGMP-dependent ICl(Ca) but only TMEM16A is important for the cGMP-independent ICl(Ca). Both proteins are important for vasomotion in mesenteric small arteries but only TMEM16A is involved in the contractile response.

Bestrophin is important for the rhythmic but not the tonic contraction in rat mesenteric small arteries

We have previously characterized a cGMP-dependent Ca(2+)-activated Cl(-) current in vascular smooth muscle cells (SMCs) and have shown its dependence on bestrophin-3 expression. We hypothesize that this current is important for synchronization of SMCs in the vascular wall. In the present study, we aimed to test this hypothesis by transfecting rat mesenteric small arteries in vivo with siRNA specifically targeting bestrophin-3. The arteries were tested 3 days after transfection in vitro for isometric force development and for intracellular Ca(2+) in SMCs. Bestrophin-3 expression was significantly reduced compared with arteries transfected with mutated siRNA. mRNA levels for bestrophin-1 and -2 were also significantly reduced by bestrophin-3 down-regulation. This is suggested to be secondary to specific bestrophin-3 down-regulation since siRNAs targeting different exons of the bestrophin-3 gene had identical effects on bestrophin-1 and -2 expression. The transfection affected neither the maximal contractile response nor the sensitivity to norepinephrine and arginine-vasopressin. The amplitude of agonist-induced vasomotion was significantly reduced in arteries down-regulated for bestrophins compared with controls, and asynchronous Ca(2+) waves appeared in the SMCs. The average frequency of vasomotion was not different. 8Br-cGMP restored vasomotion in arteries where the endothelium was removed, but oscillation amplitude was still significantly less in bestrophin-down-regulated arteries. Thus, vasomotion properties were consistent with those previously characterized for rat mesenteric small arteries. Data from our mathematical model are consistent with the experimental results. This study demonstrates the importance of bestrophins for synchronization of SMCs and strongly supports our hypothesis for generation of vasomotion.

The α2 isoform of the Na, K‐pump is involved in synchronization of smooth muscle cells in the arterial wall.

We have hypothesized that the ouabain‐sensitive Na, K‐pump can regulate smooth muscle gap junction function. To test this hypothesis and determine the relevant isoform we investigated the effect of downregulation of the α2 isoform of Na, K‐pump.We transfected cultured smooth muscle cells (SMCs) and rat small mesenteric arteries with siRNA against the α2 isoform of Na, K‐pump and with eGFP siRNA, as a control. Paired SMCs were used as a model for electrical coupling by measuring membrane capacitance and synchronized SMC activity was assessed by measuring isometric force.Pairs of SMCs had a capacitance of 90.4±9.4pF, n=7 twice that of single cells. SMCs were uncoupled when the Na, K‐pump was inhibited by 10 μM ouabain (46.1±7.2pF). β‐glycyrrhetinic acid (βGA) had no additive effect (41.9±4.9pF). Downregulation of the α2 Na, K‐pump significantly reduced the capacitance of cell pairs (33.4±4.1pF) and made them insensitive to ouabain (34.1±4.2pF). βGA uncoupled residual coupling (28.3±3.0pF). Arteries downregulated for the Na, K‐pump had significant reduced amplitude of noradrenalin‐induced vasomotion. This is consistent with the suggested role of gap junction for synchronization of SMCs in the vascular wall.We demonstrate the importance of α2 isofom of the Na, K‐pump for intercellular coupling in the vascular wall and its involvement in the regulation of vasomotion.

Longchain n-3 polyunsaturated fatty acids and microvascular reactivity: Observation in the hamster cheek pouch

Previous experiments in our laboratory, using the hamster cheek pouch microcirculation, have shown that precapillary vessels exhibit spontaneous rhythmic luminal variations, termed vasomotion, a myogenic activity sustained by a balance between membrane currents among which polarizing K + currents play an important role. In these microvessels, endothelium-derived relaxing factors (EDRFs) seem to regulate arteriolar diameter [via nitric oxide (NO) and cyclic GMP] and vasomotion [probably via endothelium-derived hyperpolarizing factor (EDHF)]. Fish or fish oil diet can decrease the risk of cardiovascular diseases, probably by modifying the conductance of selective ion channels, such as K + and/or Ca ++, and/or increasing the production of vasodilators, such as NO. To investigate its effect on microvascular reactivity, using the same preparation and an intravital microscope coupled to a closed circuit TV system, male hamsters were treated for 14 days, twice a day, with 0.4 mL/100 g body weight with fish or olive oil. An attempt was also undertaken to record in arterioles, in vivo, the membrane potential of smooth muscle cells during their vasomotor activity combining conventional microelectrode and intravital microscopy techniques. The effects of topical application of two vasodilators, acetylcholine [endothelium-dependent one, NO release and membrane hyperpolarization via Ca ++-activated K + channels (K Ca)] and sodium nitroprusside (endothelium-independent, NO donor and no change on membrane potential) and two vasoconstrictors which elicited membrane depolarization via Ca ++ channels, phenylephrine (α 1-adrenergic receptor agonist) and serotonin (5-hydroxi-tryptamine) on mean internal diameter of arterioles and venules, arteriolar blood flows, spontaneous arteriolar vasomotion frequency and amplitude and functional capillary density (FCD, number of capillaries with flowing red blood cells per unit area of tissue) were determined. Anesthesia was induced by sodium pentobarbital (i.p.) and maintained with α-chloralose through the femoral vein. In the presence of vasomotion, the membrane potentials are slowly oscillating by about 20 mV around values of approximately − 50 mV in perfect synchrony with vasomotor movements and depolarizing phases coincide with vasoconstrictions while polarizing ones with vasodilatations. Comparing all parameters, in control conditions, only the spontaneous vasomotion frequency was significantly higher (2.37 times higher) on the group treated with fish oil and persisted as such throughout all experiments. With topical application of the drugs mentioned above, the group treated with fish oil showed, for each drug concentration, a balance towards vasodilatation with consequent increase on arteriolar blood flow and on FCD, compared with the olive oil treated one. No significant changes on mean arterial pressure, spontaneous arteriolar vasomotion amplitude or venular diameter could be detected in the two groups. Our results support the concept that, in the hamster cheek pouch microcirculation, fish oil supplementation activates K + channels which act as the EDHF and might also increase the production of vasodilators, probably NO.

Effect of cyclic guanosine‐monophosphate on porcine retinal vasomotion

Vasomotion refers to periodic oscillations in vascular tone that ensure the intermittent supply of blood to adjacent microvascular units. Previous evidence from vessels outside the eye suggests that cyclic guanosine-monophosphate (cGMP) is involved in the regulation of vasomotion, but it is unknown whether this compound has an effect on vasomotion in retinal vessels. Retinal arterioles from porcine eyes were studied in a wire myograph. After initiation of vasomotion, the vessels were stimulated with increasing concentrations of the cGMP agonist 8-Br-cGMP (n = 6), the phosphodiesterase inhibitor zaprinast (n = 6) and the cGMP synthesis inhibitor L-NAME (n = 6). High concentrations of L-NAME blocked vasomotion, and control experiments (n = 20) using 8-Br-cGMP, S-nitroso-N-acetylpenicillamine (SNAP), adenosine and pinacidil were carried out to elucidate whether this effect was related to changes in the general tone of the vessel. Additionally, the relationship between oscillations in vascular tone and intracellular calcium concentration was studied. Induction of cGMP agonistic activity with either 8-Br-cGMP or zaprinast lowered the vasomotion frequency significantly, whereas L-NAME-induced inhibition of cGMP increased this frequency. Neither of the agents affected the amplitude of the oscillations. The control experiments indicated that the effect of cGMP on vasomotion frequency was independent of the accompanying increase in tone. The oscillations in tone during vasomotion were accompanied by similar oscillations in intracellular calcium concentration. Cyclic GMP lowers the frequency without affecting the amplitude of vasomotion in isolated porcine retinal arterioles.

The Physiological Effect of DE QI during Acupuncture

Acupoints tend to show higher electric conductivity and have a higher concentration of neural and vascular elements as well as mast cells. According to one model, the meridian is an extravascular fluid (interstitial fluid) pathway and circulation of this fluid is driven by skeletal muscle contraction. Our result derived from laser Doppler flowmetry shows that Yanglao (SI6) and Xiaohai (SI8) have larger amplitude of heartbeat and vasomotion than non-acupuncture points. The amplitude of blood flow on the SI8 shows a more significant increase (4.3 ± 0.7 PU) than that of non-acupuncture points (1.1 ± 0.2 PU). Our results indicate that acupuncture increases blood flow when the De-Qi sensation takes place. In the experiment, the needle was only entered into the subject by 2 mm for about 15 sec during a SI6 acupuncture session, and the blood flow increased immediately. The blood flow of SI8 began to rise 5 sec after implementation and increased by 11.1 ± 0.9 PU. However, when the arm was tied up, the blood flow at the SI8 point slowed down quickly. Even though insertion with a twirling needle was followed after the drop in blood flow, the blood flow at the SI8 point did not accelerate again (0.7 ± 0.2 PU). The present study seems to show that acupuncture is effective in regulating the autonomic nervous system. Implementation of acupuncture causes the sphincter of microvessel to relax, and the tissue fluid to flow out, and the propagated sensation along the meridian is caused by this large amount of tissue fluid that flows along the loosen body stalk. The interstitial fluid increases during the needling and blood capillary expansion, which may be one of the mechanisms of acupuncture regulation.

Temporal variations in testicular microcirculation.

Temporal variations in microcirculatory blood flow in the testis and blood pressure were examined in intact, pentobarbital-anesthetized rats with a two-channel laser Doppler flowmeter. The laser Doppler probes that measure local blood flow in a tissue volume of about 2 mm3 were placed either over the mid portion of the left and right testes or on the right testes 1 cm apart. Testicular microcirculation was characterized by a prominent vasomotion with a frequency of 5.3+/-1.4 cycles per minute and with an amplitude of 73+/-32% (mean +/- SD) of the mean. In addition to this large and rapid variation in local blood flow, there were also major variations from minute to minute in the average blood flow, vasomotion frequency, and vasomotion amplitude at 40 and 53 minutes. Such variations in local blood flow, vasomotion frequency, and vasomotion amplitude were correlated with each other at two different sites on the same testis (r(s) = 0.39, r(s) = 0.82, r(s) = 0.64, respectively, P < 0.001), and they were all correlated with systemic blood pressure (r(s) 0.41, r(s) = 0.61, r(s) = 0.32, respectively, P < 0.001). Minute-to-minute variations in local blood flow, vasomotion frequency, and vasomotion amplitude were also correlated between the right and left testes (r(s) = 0.58, r(s) = 0.75, r(s) = 0.57, respectively, P < 0.001). There are substantial temporal variations in testicular microcirculation. These variations are to some extent related to temporal changes in systemic blood pressure, but changes in the ultralocal environment are probably more important. The functional significance of, and the factors responsible for, local variations in testicular microcirculation remain to be elucidated.

Modulation of vasomotion in resistance arteries of JCR:LA-cp rats: a model of insulin resistance

Obesity and insulin resistance are strongly associated with an increased risk of vascular disease. Vasomotion is the cyclic variation in the diameter of arteries and is a general feature of the vasculature that may have important physiological consequences. We tested the hypothesis that obesity - insulin resistance is associated with abnormal vasomotion by comparing obese, insulin-resistant JCR:LA-cp rats, known to develop vasculopathy, atherosclerosis, and ischemic lesions of the heart, with lean insulin-sensitive animals from the same strain. Vasomotion was assessed using isolated mesenteric arteries on a myograph system after preconstriction to 50% of maximal constriction with norepinephrine. The amplitude of vasomotion was enhanced by the presence of meclofenamate, a prostaglandin H synthase inhibitor, and was diminished by NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. Removal of the endothelium essentially abolished vasomotion, and meclofenamate had no effect on de-endothelialized arteries. Frequency was not altered by either L-NAME or meclofenamate. Although pharmacological inhibition of nitric oxide and eicosanoid production clearly altered vasomotion, there was no difference in the amplitude or frequency of vasomotion in arteries from obese rats compared with lean rats. These results indicate that the endothelium plays a central role in modulating vasomotion, involving both enhancing and inhibiting effects, and that vasomotion is similar between obese, insulin-resistant and lean, insulin-sensitive rats.Key words: insulin resistance, vasomotion, resistance arteries, JCR:LA-cp rats.

Modulation of vasomotion in resistance arteries of JCR:LA-cp rats: a model of insulin resistance

Obesity and insulin resistance are strongly associated with an increased risk of vascular disease. Vasomotion is the cyclic variation in the diameter of arteries and is a general feature of the vasculature that may have important physiological consequences. We tested the hypothesis that obesity - insulin resistance is associated with abnormal vasomotion by comparing obese, insulin-resistant JCR:LA-cp rats, known to develop vasculopathy, atherosclerosis, and ischemic lesions of the heart, with lean insulin-sensitive animals from the same strain. Vasomotion was assessed using isolated mesenteric arteries on a myograph system after preconstriction to 50% of maximal constriction with norepinephrine. The amplitude of vasomotion was enhanced by the presence of meclofenamate, a prostaglandin H synthase inhibitor, and was diminished by N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. Removal of the endothelium essentially abolished vasomotion, and meclofenamate had no effect on de-endothelialized arteries. Frequency was not altered by either L-NAME or meclofenamate. Although pharmacological inhibition of nitric oxide and eicosanoid production clearly altered vasomotion, there was no difference in the amplitude or frequency of vasomotion in arteries from obese rats compared with lean rats. These results indicate that the endothelium plays a central role in modulating vasomotion, involving both enhancing and inhibiting effects, and that vasomotion is similar between obese, insulin-resistant and lean, insulin-sensitive rats.