Biomedical subjects

A Colantuoni

Publications and source records attributed to A Colantuoni.

At least 19 recordsLinked to original sources

PubMed2005

Protective effects of insulin during ischemia-reperfusion injury in hamster cheek pouch microcirculation.

OBJECTIVE: The effects of insulin (0.18 nM-0.18 microM) on reduced capillary perfusion, microvascular permeability increase and leukocyte adhesion induced by ischemia-reperfusion injury were investigated in the hamster cheek pouch microcirculation. To gain insight into the insulin's mechanism of action, the effects of its higher concentration (0.18 microM) were investigated after inhibition of tyrosine kinase (TK), nitric oxide synthase (NOS), protein kinase C (PKC), phosphatidylinositol 3-kinase and K+(ATP) channels, alone or in combination. Two concentrations for each inhibitor were used. METHODS: Microcirculation was visualized by fluorescence microscopy. Perfused capillary length, microvascular permeability, leukocyte adhesion to venular walls, vessel diameter and capillary red blood cell velocity were assessed by computer-assisted methods. Measurements were made at baseline (B), after 30 min of ischemia (I), and after 30 min of reperfusion (R). RESULTS: In control animals, perfused capillary length decreased by 63 +/- 5% of baseline at R. Microvascular permeability increased at I and R, while leukocyte adhesion was most pronounced in V1 postcapillary venules at R. Insulin dose-dependently preserved capillary perfusion at R (-28 +/- 6 and -15 +/- 6% of baseline), but was unable to prevent the increase in permeability at I (0.25 +/- 0.05 and 0.29 +/- 0.06 Normalized Grey Levels, NGL) and R (0.49 +/- 0.10 and 0.53 +/- 0.09 NGL), according to the concentrations. Adhesion of leukocytes was observed mostly in V3 venules at R (9 +/- 2 and 10 +/- 2/100 microm venular length, with the lower and higher concentration, respectively). Nitric oxide synthase inhibition by N(G)-nitro-L-arginine-methyl ester prior to insulin did not affect capillary perfusion at R (-18 +/- 3% of baseline with higher concentration), but prevented permeability increase (0.20 +/- 0.04 NGL, according to higher concentration) and reduced leukocyte adhesion in V3 venules at R (1.5 +/- 1.0/100 microm of venular length, with higher concentration). Blockade of K+(ATP) channels by glibenclamide prior to insulin decreased perfused capillary length at R (-58 +/- 6% of baseline with higher concentration), attenuated leakage at R (0.30 +/- 0.04 NGL, according to higher concentration) and caused leukocyte adhesion mainly in V1 venules at R (9.0 +/- 1.5/100 microm of venular length, with higher concentration). Inhibition of either TK, PKC or phosphatidylinositol 3-kinase did not affect microvascular responses to insulin. Simultaneous inhibition of TK and NOS did not increase protection. CONCLUSIONS: Insulin prevents ischemia-reperfusion injury by promoting capillary perfusion through an apparent activation of K+(ATP) channels and increase in nitric oxide release.

Alkaloids↗

PubMed2004

Effects of tetraiodothyronine and triiodothyronine on hamster cheek pouch microcirculation.

The aim of the present study was to assess the effects of topically applied triiodothyronine (T(3)) and thyroxine (T(4)) on the arterioles of hamster cheek pouch microcirculation in vivo. Microvessels were visualized using a fluorescent microscopy technique. Topical application of T(3) (3.08, 30.8, 61.5, 307, 615, and 6,150 nM/l) consistently induced dose-dependent dilation of arterioles within 2.0 +/- 0.5 min of administration. The application of T(4) (150, 257, 514, and 5,140 nM/l) caused different dose-dependent effects: dilation at the three lower doses within 16 +/- 2 min and rhythmic diameter changes at the highest dose. Aging of hamsters did not alter the arteriolar responses to T(3) and T(4). T(3)-induced dilation was countered by the inhibition of nitric oxide synthase with N(G)-nitro-L-arginine-methyl ester or N(G)-nitro-L-arginine. Iopanoic acid (IPA), which inhibits types I and II 5'-deiodinase, abolished the dilation elicited by 514 nM T(4) but did not affect T(3)-dependent dilation. 6-Propyl-2-thiouracil (PTU), which inhibits type I 5'-deiodinase only, did not affect the dilation induced by T(4). IPA and PTU did not impair arteriolar dilation induced by acetylcholine or sodium nitroprusside. These results indicate that T(3) induces arteriolar dilation, likely through nitric oxide release. The local conversion of T(4) to T(3) appears to be crucial for the dilation induced by T(4).

Animals↗

PubMed2002

Retinal photoreceptors of Syrian hamsters undergo oxidative stress during streptozotocin-induced diabetes.

AIMS/HYPOTHESIS: The aim of this study was to verify whether retinal photoreceptors, like other tissues, are subject to oxidative stress during diabetes. METHODS: Oxidative stress was monitored by the oxidation of preloaded dehydrorhodamine 123 into fluorescent rhodamine 123, during a period of intense illumination of isolated rod retinal receptor cells. These were obtained from 22 Syrian hamsters injected with streptozotocin (50 mg/kg body weight., intraperitoneal route) 90 days before the study began. Eleven hamsters were treated daily with melatonin (0.4 mg/kg body wt., per os), an antioxidant synthesized within photoreceptors. Isolated photoreceptors were bathed on the stage of a Leitz Orthoplan microscope, where the fluorescent lamp also served as the light stimulus (485 nm). Fluorescence irradiance was measured by photometry and stored in a personal computer for further analysis. RESULTS: The light-induced oxidant production greatly decreased and was also delayed in the streptozotocin-injected hamsters compared with the control hamsters matched for age. Similar effects were obtained in control photoreceptors after 40 min incubation with 2-2'-azobis (2-amidinopropane) dihydrochloride, a potent lipoperoxidation inducer. The effect of melatonin was to partially restore the light-induced fluorescence response. CONCLUSION/INTERPRETATION: The depression of the light-induced oxidative response in diabetic photoreceptors could be ascribed to a hyperglycaemia-induced background of oxidative stress whereby the light-oxidizable substrate is actually lowered. Melatonin induces a larger fluorescence response during illumination, probably as a consequence of its antioxidant effect during diabetes, which would provide more oxidizable lipids.

Amidines↗

PubMed2001

Phentolamine suppresses the increase in arteriolar vasomotion frequency due to systemic hypoxia in hamster skeletal muscle microcirculation.

Systemic hypoxia (8%, 11% and 15% oxygen gas mixture inspiration) has been shown to increase the frequency of arteriolar rhythmic diameter changes in hamster skeletal muscle microcirculation. The effects of phentolamine on vasomotion frequency during systemic hypoxia were studied in Syrian hamsters implanted with a plastic chamber in the dorsum skin. Phentolamine (50 microg/100 g body wt.) was injected intravenously before the 20-min exposure to 11% oxygen gas mixture. The microvessels were studied with a fluorescent microscopy technique, using fluorescein isothiocyanate bound to dextran (mol. wt. 150,000) as a tracer. Vessel diameters were measured with a shearing method. Fourier transform and autoregressive modeling were used to assess the time variant features of diameter changes. Under baseline conditions, the arterioles were characterized by rhythmic diameter changes with fundamental frequency related to vessel size. The terminal branchings were dominated by order 3 vessel activity (frequency: 0.08-0.16 Hz) spreading downstream to all daughter arterioles. Systemic hypoxia caused an increase in vasomotion frequency of order 3 arterioles up to 0.3-0.5 Hz (average: 0.40 +/- 0.06 Hz) and a significant decrease in mean diameter (-28 +/- 5%). Phentolamine completely suppressed the rhythmic changes in diameter of order 3 arterioles that dilated significantly (+ 30 +/- 4%). Therefore, the effects of systemic hypoxia on arteriolar vasomotion appear to be triggered by an increase in sympathetic nervous discharge that induces a rise in frequency up to 0.3-0.5 Hz.

Animals↗

PubMed2000

Protective effects of leukopenia and tissue plasminogen activator in microvascular ischemia-reperfusion injury.

Ischemia shifts the anticoaugulant/procoagulant balance of the endothelium in favor of activation of coagulation. We studied whether cheek pouch microcirculation of leukopenic hamsters was protected by tissue plasminogen activator (tPA) (50 microg/100 g body wt) against ischemia-reperfusion injury. Adherent leukocytes, total perfused capillary length (PCL), permeability increase, and arteriolar and venular red blood cell (RBC) velocity were investigated by fluorescence microscopy. Measurements were made at control, 30 or 60 min of ischemia, and at 30 or 60 min of reperfusion. Hamsters were made leukopenic by treatment with cyclophosphamide (20 mg/100 g body wt ip, 4 days before the experiment), which decreased circulating leukocyte count by 85-90%. Leukopenic hamsters undergoing 30 min of ischemia followed by 30 min of reperfusion showed no significant decrease in PCL or increased permeability. Leukopenic hamsters undergoing 60 min of ischemia followed by 60 min of reperfusion presented a significant decrease in microvascular perfusion where PCL was 28 +/- 7% of baseline, low-flow conditions, and increased permeability. In leukopenic hamsters treated with tPA there was complete protection of capillary perfusion with no significant changes in permeability or arteriolar and venular RBC velocity. In conclusion, thrombus formation may be an additional and independent factor that with leukocyte-mediated mechanisms determines ischemia-reperfusion injury.

Animals↗

PubMed1999

Red blood cell velocity and volumetric flow assessment by enhanced high-resolution laser Doppler imaging in separate vessels of the hamster cheek pouch microcirculation.

An enhanced high-resolution laser Doppler imager (EHR-LDI), configured to fit the demands of a measurement area containing separate microvessels, was evaluated for perfusion measurements in hamster cheek pouch preparations during ischemia, reperfusion, and pharmacologically induced vasodilation and vasoconstriction. Measurements in separate microvessels where the laser beam was smaller than the vessel diameter were referred to as red blood cell (RBC) velocity estimates, as previously validated in vitro, whereas a relative flow index, RFI (mean RBC velocity/tissue area), was introduced as a volumetric flow measure. Microvessel diameter and RBC velocity changes during ischemia, reperfusion, as well as during vasoconstriction and vasodilation correlated to the data obtained from the microscope. Correspondingly, during the described provocations anticipated volumetric flow changes were registered as changes in the RFI. When data on intravessel RBC velocity profiles are presented they reflect a parabolic flow profile usually seen in this size microvessel. The EHR-LDI appears a promising tool for investigation of the microvasculature, as it almost simultaneously provides information on relative changes of both in vivo RBC velocity and volumetric flow (RFI), although the latter estimate needs to be further refined.

Adenosine↗

PubMed1999

Time-variant spectral analysis of LDF signals on the basis of multivariate autoregressive modelling.

Time-variant AR-modelling was used to analyse the non-stationary properties of LDF signals during provocation tests. The procedure for the estimation of time-varying AR parameters based on Kalman filtering is presented. The estimates can be used to calculate instantaneous measures, such as peak frequency, spectral band power and coherence. The resulting course of instantaneous peak frequency of a sinusoidal signal with frequency jump was compared to similar parameters derived from short-time FFT and Hilbert transformation. Univariate time-variant spectral analysis was used to investigate LDF measurements in patients with Raynaud's phenomena. The experimental protocol was splitted into phases of different room temperature. The results demonstrate time-dependent variations of spectral components (amplitude and frequency). By means of time-variant coherence analysis of LDF and diameter measurements of vessels in a hamster skin fold the existence of a main rhythm around 0.1 Hz in the LDF signals which is related to vasomotion is shown.

Algorithms↗

PubMed1999

Different flowmotion patterns in healthy controls and patients with Raynaud's phenomenon.

Flowmotion was characterized in healthy controls and 61 Raynaud's phenomenon (RP) patients by spectral analysis of laser-Doppler perfusion monitoring (LDPM) tracings. Healthy subjects flowmotion patterns revealed a main frequency of 3 cycles per min (cpm) with another low frequency and heart rate synchronous components. A first group of RP patients presented a low frequency and heart rate frequency component but no significant difference in blood flow. The second group presented the predominating heart rate related frequency with low microvascular perfusion. The third group presented a flowmotion pattern with overlapping of heart rate and low frequency components. Patients with primary and secondary RP show specific changes in flowmotion, probably related to increased sympathetic nervous activity or vessel wall alterations causing disappearance of arteriolar tone and impairment of microvascular perfusion. The group of patients with overlapping frequency components presents an intermediate flowmotion pattern indicating a different grade of alterations in microvasculature.

Adolescent↗

PubMed1998

Capillary density and leukocyte adhesion in hamsters with hereditary cardiomyopathy.

The aim of this study was to characterize microvascular networks in cheek pouch of cardiomyopathic Syrian hamster (CM) (Bio 14.6), which is an interesting model of idiopathic cardiomyopathy and congestive heart failure. Microcirculation was visualized by fluorescence microscopy. Diameter and length of arterioles, classified according to centrifugal ordering scheme, were measured. A computational method was arranged to determine the density of arterioles and capillaries (total vessel length per unit area, cm-1), fractal dimension of capillaries, and the associated Voronoi tesselation. Furthermore, leukocyte adhesion to venules and arteriolar reactivity to drugs were studied. Increase in the number of terminal arterioles and capillary rarefication characterized CM microvasculature compared with that of age-matched controls (58 +/- 7 versus 25 +/- 5 cm-1, and 128 +/- 15 versus 240 +/- 10 cm-1, respectively). Fractal dimension of capillaries was reduced in CM compared with controls (1. 40 +/- 0.10 versus 1.85 +/- 0.09) and associated with increased avascular spaces, as shown by Voronoi tesselation results. Leukocyte adhesion to venules increased significantly in CM. In CM responsiveness of arterioles to nitric oxide inhibition and propranolol was slighter but more marked to norepinephrine and angiotensin II compared with that of control hamsters. In conclusion, the different geometry, increased leukocyte adhesion, and altered arterial responsiveness may contribute to flow disturbances in the microcirculation of CM hamsters.

Animals↗

PubMed1998

Evaluation of enhanced high-resolution laser Doppler imaging in an in vitro tube model with the aim of assessing blood flow in separate microvessels.

An enhanced high-resolution laser Doppler imaging (EHR-LDI) technique intended for visualization of separate microvessels was evaluated by use of in vitro flow models. In EHR-LDI, a laser beam focused to a half-power diameter less than 40 microm successively scans the tissue under study in steps of 25 microm. Spatial blood flow variations within microvascular structures of 1.5 x 1.5 mm are rendered by 64 x 64 measurement sites. Individual microvessel diameters could be estimated and an average difference of 11 microm compared to microscopic measurements was obtained. For the flow algorithm used, the LDI output signal was found to scale linearly with average velocity (0-3.5 mm/s) when a plastic tube of inner diameter 175 microm was perfused with human blood (correlation coefficient 0.99). The LDI output signal was further found insensitive to hematocrit variations in the range 16-44%. Due to the limited laser light penetration in blood, a reduction in the LDI output signal was observed as the inner tube diameters were successively changed from 280 to 1400 microm.

Animals↗

PubMed1998

Vasomotion and blood flow regulation in hamster skeletal muscle microcirculation: A theoretical and experimental study.

A mathematical model of a microvasculature was used to study the effects of myogenic and flow-dependent stimuli on the characteristics of vasomotion and microvascular perfusion regulation. The model includes three branching orders of arterioles derived from in vivo observations and incorporates a mechanism for terminal arteriolar closure during vasomotion. Simulations were performed to evaluate the effect of vasodilation and vasoconstriction on vasomotion pattern, and the changes in arteriolar effective diameter and flow in response to arterial blood pressure variations triggering the regulatory mechanisms. Vasomotion patterns were studied in the hamster cutaneous muscle, visualized by fluorescent microscopy, in control conditions and after injection of acetylcholine (Ach) or NG-monomethyl-L-arginine (L-NMMA). We have found that vasomotion may be caused by different combinations of feedback mechanisms, including a strong rate-dependent myogenic response or a strong flow-dependent mechanism with no rate-dependent response. Decreasing the rate-dependent component of the myogenic mechanism and increasing the time constant of the flow-dependent mechanism causes vessel stabilization and disappearance of vasomotion. In hamster microcirculation, Ach decreased vasomotion frequency and increased vasomotion amplitude and arteriolar effective diameter, whereas L-NMMA caused a slight increase in vasomotion frequency and decrease in effective diameter. Model simulations, under dilatory and constrictory stimuli, confirmed these results. Moreover, the model predicted that mean blood flow is maintained closer to normal despite arterial pressure changes (+/-15% flow changes versus +/-50% pressure variations) when the vessels were in nonoscillatory than when they are in oscillatory state. In conclusion, a large variety of vasomotion patterns affect arteriolar resistance and microvessel perfusion in skeletal muscle. Furthermore, in the presence of vasomotion the network exhibits a poorer aptitude for regulating blood flow during arterial pressure changes (i.e., worse autoregulation) than the nonoscillatory network.

Animals↗

PubMed1997

Venular oscillatory flow during hemorrhagic shock and NO inhibition in hamster cheek pouch microcirculation.

Blood flow oscillations (flowmotion) during hemorrhagic shock (HS) were recorded with laser Doppler perfusion monitoring (LDPM) and red blood cell (RBC) velocimetry in arterioles and venules in hamster cheek pouch microcirculation. Experiments were carried out after baroceptor denervation or inhibition of nitric oxide (NO) synthesis with NG-monomethyl-L-arginine prior to and during HS. Flowmotion was characterized by spectral analysis with fast Fourier transform and autoregressive modeling. Low frequency flowmotion was detected in LDPM and RBC velocity tracings derived from arterioles while high frequency oscillations dominated in venules under baseline conditions. Venular blood flow was significantly higher compared with arteriolar flow during HS, while large amplitude low frequency flowmotion was found in venules but not in arterioles where dominated small amplitude high frequency oscillations coincident with respiratory or heart rates. Baroceptor denervation did not affect venular blood flow and low frequency flowmotion during HS. NO inhibition reduced significantly venular blood flow compared with control and abolished low frequency flowmotion in venules. High frequency oscillations remained in arterioles during HS. In conclusion, LDPM low frequency flowmotion was not originated by variations in the diameter of vessels, but corresponded to RBC velocity changes. A compensatory higher blood flow and concomitant low frequency flowmotion in venules appeared to be related to NO production during HS, independently of neural mechanism.

Animals↗

PubMed1996

Theoretical analysis of complex oscillations in multibranched microvascular networks.

A mathematical model was used to study the origin of complex self-sustained diameter oscillations in multibranched microvascular networks. The model includes three branching levels (order 3, 2, and 1 arterioles) of a microvascular network derived from in vivo observation in the hamster dorsal cutaneous muscle. The main biomechanical aspects covered by the model are (1) the dependence of the elastic and active wall stress on the inner radius and (2) the static and dynamic myogenic response. Simulations on isolated arterioles indicate that self-sustained periodic diameter oscillations may occur at constant transmural pressure. Conversely, simulations on the entire network reveal different oscillatory patterns, including periodic, quasiperiodic, and chaotic fluctuations. Chaos in the model is revealed by the presence of a broad noise-like component in the frequency spectrum and by the sensitivity dependence of model results on small perturbations. Our results suggest that, owing to the intrinsic nonlinearity of the system, a contracting mechanism, such as the myogenic response, may induce different oscillatory patterns. The change from periodic to chaotic oscillations may be a consequence of a modest variation in a parameter (systemic pressure or arterial resistance) not necessarily related to pathophysiological conditions. Accordingly, our in vivo observations in the skeletal muscle showed that in some instances arteriolar vasomotion is converted from regular to highly irregular patterns in basal conditions. Vasomotion is found to affect mean blood flow compared with the nonoscillatory steady state. Chaotic oscillations tend to maintain a constant ratio of blood flows entering into bifurcation vessels, whereas periodic vasomotion determines a different flow distribution at branches.

Animals↗

PubMed1996

Dynamic coherence analysis of vasomotion and flow motion in skeletal muscle microcirculation.

The aim of our study was to determine the cause of fluctuations in microvascular blood flow measured by laser Doppler perfusion monitoring (LDPM) in microvessels of the hamster skin fold preparation. LDPM flow fluctuations (flow motion) were compared to simultaneous records of diameter changes obtained from arterioles and venules. Time-varying coherence analysis was used to quantify the frequency of flow and diameter changes in awake hamsters in control conditions and during sodium nitroprusside-induced vasodilation. Power spectrum analysis of LDPM signals of order 4 and 3 arterioles indicated frequencies of 0.06 +/- 0.01 and 0.08 +/- 0.02 Hz, respectively. Order 3 arterioles exhibited significant temporal coherence between flow motion and vasomotion signals at a frequency of the order of 0.1 Hz. There was lack of coherence when vasomotion was absent in arterioles. Order 4 arterioles had several coherent frequencies in addition to that around 0.1 Hz. In conclusion, time-variant coherence analysis indicated that spontaneous fluctuations in flow are caused by vasomotion of order 3 arterioles with frequency around 0.1 Hz that appears to coordinate local control processes in the microcirculation. Additional frequency components present in LDPM signals are unrelated to vasomotion.

Animals↗

PubMed1996

Melatonin prevents ischemia reperfusion injury in hamster cheek pouch microcirculation.

OBJECTIVE: We used the hamster cheek pouch microcirculation to investigate the effects of melatonin (ME) on ischemia reperfusion (I-R) injury by in vivo microscopy. ME is a hormone produced by the pineal gland and is the most powerful and effective hydroxyl radical scavenger detected to date in vitro. The second aim was to determine the scavenger effect of ME in cheek pouch microcirculation when topically applying an oxygen-derived free radical generating system. METHODS: Ischemia was induced by clamping the cheek pouch for 30 min followed by 30 min of reperfusion. We quantified the increase in permeability, the perfused capillary length and leukocyte adhesion by computerized methods. Microcirculation was also exposed to a hypoxanthine-xanthine oxidase (H-X) system. RESULTS: In control hamsters I-R was associated with increased permeability, increased number of leukocytes sticking to venules, and decreased perfused capillary length. Treatment with ME completely inhibited microvascular edema formation and reduced the number of leukocytes sticking to venules after reperfusion. Moreover, ME prevented the marked decrease in perfused capillary length, preserving microvascular perfusion. ME topically applied reduced significantly the permeability increase due to H-X exposure. CONCLUSIONS: The beneficial effect of ME may be related to its antioxidant properties. These protect the endothelial barrier integrity as well as preserve microvascular blood perfusion by dysfunctions after I-R.

Animals↗

PubMed1995

Capillary reperfusion after L-arginine, L-NMMA, and L-NNA treatment in cheek pouch microvasculature.

The effects of arginine (L-arg), promoter of nitric oxide (NO) production and NO synthesis inhibitors, NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine (L-NNA), on arteriolar responses and capillary perfusion after 30 min ischemia were studied in the cheek pouch preparation under pentobarbital anesthesia and intravenous drug infusion. Capillary density, venular leukocyte sticking, and vessel diameters were investigated by fluorescence microscopy. Damage due to photoactivation of intravascular dyes was investigated by injecting fluorescent dextran 150,000 MW prior to and after ischemia reperfusion. No difference was found indicating that effects were independent from exposure time to photoactivated dyes. Capillary perfusion reduction was always present after reperfusion in untreated, L-NMMA-treated, and L-NNA-treated animals, with increased venular leukocytes adhesion. Arteriolar vasomotion was induced by L-NMMA treatment. Capillary perfusion recovered in L-arg-treated hamsters, where capillary blood flow velocity was lower than in L-NMMA group and the number of adhering leukocytes was lower than in untreated controls, L-NMMA, and L-NNA groups. It is concluded that L-arg determines perfusion with increased blood flow heterogeneity while inhibition of NO preserves capillary perfusion causing appearance of vasomotion in the arterial network.

Animals↗

PubMed1995

Effects of the natural flavonoid delphinidin on diabetic microangiopathy.

The purpose of the present study was to investigate the effects of the flavonoid delphinidin chloride (CAS 528-53-0, IdB 1056) on diabetic microangiopathy. Hamsters were injected with alloxan and cheek pouch microcirculation was observed by a fluorescent microscopy technique 90 days from alloxan. The increase in permeability, the number of adhering leukocytes to venular vessel wall and vasodilatory responses to acetylcholine (Ach) and sodium nitroprusside (SNP) were measured. In diabetic group microvascular permeability and the number of sticking leukocytes to the venular endothelium were increased. Vasoconstriction by Ach was observed while the vasodilation by SNP was significantly attenuated in diabetic animals. These results are consistent for a decreased relaxation and suggest also an impairment in the smooth muscle cell function in diabetic arterioles. IdB 1056 exhibited an inhibitory effect on increased microvascular permeability and on leukocytes adhering to the venular vessels. Indeed, the treatment with IdB 1056 in diabetic hamsters pretreated or not with indometacin, a cyclooxygenase inhibitor, restored the relaxant responses to Ach and SNP. In conclusion, the effects of IdB 1056 observed in vivo at the microcirculatory level prevent the injury to endothelial cell function associated with diabetes and/or oxidative stress.

Acetylcholine↗

PubMed1994

Effects of L-NMMA and indomethacin on arteriolar vasomotion in skeletal muscle microcirculation of conscious and anesthetized hamsters.

The purpose of this study was to determine the influence of NG-monomethyl-L-arginine (L-NMMA) and indomethacin (INDO), respectively inhibitors of nitric oxide synthase and cyclooxygenase, on spontaneous arteriolar activity (vasomotion) in the skeletal muscle of awake and anesthetized hamsters. Unanesthetized hamsters, implemented with the skin fold chamber window, displayed vasomotion, whose frequency and amplitude were quantified by power spectrum analysis. Intravenous administration of L-NMMA significantly increased vasomotion frequency and did not change the amplitude at the lower dose, but in order 3 arterioles amplitude decreased significantly. With higher doses L-NMMA caused constriction of order 1-2 vessels, frequency decreased and amplitude increased, and the arteriolar vasodilator response to acetylcholine decreased significantly. During anesthesia topically applied L-NMMA significantly decreased diameter and caused the appearance of vasomotion in order 1-2 arterioles. INDO did not affect vasomotion in unanesthetized hamsters and did not initiate vasomotion during anesthesia leading to the conclusion that prostaglandins do not regulate vasomotion. Vasomotion is not directly related to nitric oxide (NO) in conscious animals while NO blockage stimulates vasomotion in smaller arterioles of anesthetized hamsters without vasomotion; however, the simultaneous inhibition of cyclooxygenase and NO had no effect on arteriolar diameter during anesthesia. It is concluded that vasomotion is regulated by a mechanism that modulates smooth muscle cell activity through the endothelium.

Acetylcholine↗