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At least 649 records · Page 36Linked to original sources

PubMed2006

Dynamic changes of post-ischemic hepatic microcirculation improved by a pre-treatment of phosphodiesterase-3 inhibitor, milrinone.

BACKGROUND: Phosphodiesterase-3 inhibition has been shown to attenuate hepatic warm ischemia-reperfusion injury. The aim of this study was to investigate the effect of milrinone, phosphodiesterase-3 inhibitor, on post-ischemic microcirculation of rat livers by intravital microscopy. MATERIALS AND METHODS: Male Wistar rats were randomly assigned to three groups; group A, milrinone pre-treatment; group B, ischemic pre-conditioning; and group C, no pre-treatment. All animals underwent a 60-min warm ischemia of the left lateral liver lobe. Microvascular perfusion and leukocyte-endothelial interaction were observed by intravital videomicroscopy. Hepatocellular viability and cellular damage were quantified by adenosine triphosphate tissue concentration as well as alanine aminotransferase and lactate dehydrogenase blood levels, respectively. RESULTS: In groups A and B, cyclic AMP hepatic tissue concentration was elevated significantly. After reperfusion, microvascular perfusion in hepatic sinusoids was significantly better maintained, and the number of adherent leukocytes was reduced in sinusoids and in post-sinusoidal venules in these rats. Serum transaminase blood levels were suppressed significantly in these groups compared with controls. CONCLUSION: The demonstrated improvement of hepatic microcirculation is certainly derived from milrinone induced cell protection in ischemia reperfusion of the liver. This effect is outlined by improved energy status and reduced liver enzyme liberation and mimics the effect of ischemic pre-conditioning.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2005

Insulin enhances leukocyte-endothelial cell adhesion in the retinal microcirculation through surface expression of intercellular adhesion molecule-1.

The purpose of this study was to evaluate the effects of insulin on leukocyte-endothelial cell adhesion in the retinal microcirculation in vitro and in vivo. Human retinal endothelial cells (HRECs) were cultured in medium with or without insulin, and neutrophils allowed to adhere. Adherent neutrophils were quantified by measuring myeloperoxidase activity. Surface expression of endothelial adhesion molecules were studied with the use of an enzyme immunoassay. Insulin at concentrations of 50 and 100 microU/ml significantly increased neutrophil adhesion to HRECs compared with the control cells (P < 0.01, respectively). Surface expression of intercellular adhesion molecule-1 (ICAM-1) significantly increased when HRECs were exposed to 100 microU/ml insulin, as compared with the control cells (P < 0.05). Anti-ICAM-1 antibody significantly inhibited neutrophils adhesion to HRECs (P < 0.0001). Brown-Norway rats received subcutaneous injection of 0.2 U per 100 g body weight insulin three times. Control rats received the same amount of phosphate-buffered saline. Leukocyte entrapment in the retina was evaluated using acridine orange leukocyte fluorography. The number of leukocytes trapped in the retina of insulin-treated rats was significantly elevated compared with that in the control animals (P < 0.0001). These results suggested that insulin enhances leukostasis in retinal microcirculation. Hyperinsulinemia may be a risk factor of retinal microcirculatory disturbances.

Acridine Orange↗

PubMed2006

ICAM-1 expression and leukocyte behavior in the microcirculation of chronically ischemic rat skeletal muscles.

In muscle microcirculation, short periods of ischemia followed by reperfusion are known to upregulate leukocyte and endothelial adhesion molecules, but little is known about leukocyte adherence and ICAM-1 expression during chronic ischemia or any likely effect of muscle activity which is recommended in chronic ischemia due to peripheral arterial disease. Leukocyte rolling and stationary adhesion were observed in post-capillary venules in ischemic and contralateral rat extensor digitorum longus (EDL) muscles 3 and 7 days after unilateral ligation of the common iliac artery and in 3-day ischemic EDLs that were electrically stimulated on days 1 and 2 post-ligation (7 x 15 min per day). ICAM-1 was localized immunohistochemically to venular vessels in all muscles. Following ligation, use of the ischemic leg was observed to be restricted for the first 3 days, returning to normal by 7 days. After 3 days, leukocyte rolling/adherence and ICAM-1 expression were no different in ischemic than control muscles, but all were increased in contralateral muscles. In ischemic muscles, electrical stimulation doubled the numbers of rolling leukocytes and upregulated ICAM-1 expression. After 7 days, increased muscle activity as a result of natural movement also resulted in greater ICAM-1 expression, a 4- to 5-fold increase in rolling leukocyte numbers and a 3-fold increase in stationary adherent leukocytes. Chronic ischemia thus increases ICAM-1 and leukocyte adherence in muscle microcirculation only when combined with contractile activity. Post-capillary venular endothelium may be modified by muscle acidosis when contractions are performed under low flow conditions or by changes in rheological (shear force) factors.

Animals↗

PubMed2006

Multi-image particle tracking velocimetry of the microcirculation using fluorescent nanoparticles.

Particle tracking velocimetry provides a Lagrangian description of flow properties in the microcirculation. To determine the utility of fluorescent nanoparticles to provide Lagrangian coordinates, we tracked these particles both in vitro and in vivo. The particles had a neutral charge and fluorescence intensity greater than 1,000 times the PKH26-labeled red blood cells. At image acquisition rates of 60 frames per second, particles were tracked at velocities up to 4,000 microm/s. Morphometric changes reflecting streaking artifact were significant at velocities of 4,000 microm/s (P < 0.05), but not at lower velocities (P > 0.05). Intravital microscopy monitoring after intravenous injection of the particles demonstrated a circulation half-life that was inversely related to particle size: 500 nm nanoparticles demonstrated a smaller change in plasma concentration than larger particles. Regardless of the size of the particles, more than 50% of the recovered fluorescence was located in the liver. These results suggest that fluorescent nanoparticles provide a convenient and practical Lagrangian description of flow velocity in the microcirculation.

Animals↗

PubMed2006

Bicyclic monoterpene diols stimulate release of nitric oxide from skin cells, increase microcirculation, and elevate skin temperature.

Bicyclic monoterpene diols (BMTd) stimulate nitric oxide synthesis in melanoma and neuronal cells, representing cell types arising from embryonic neural crest tissue. This study shows that an equimolar mixture of the BMTd's 2,3-cis/exo-pinanediol and 2,3-cis/exo-camphanediol stimulates nitric oxide synthesis in epithelial cells of the skin, specifically normal human epidermal keratinocytes (NHEK) and normal human microvascular endothelial cells (HMVEC). A 1 mM mixture increased nitric oxide 3-fold in HMVEC in the first 24 h after treatment, and a 2 mM mixture produced an equivalent increase in NHEK. We hypothesized that an increase in nitric oxide in skin would lead to an increase in microcirculation, thereby increasing skin temperature. We found that twice daily application of 1mM BMTd lotion significantly increased arm skin temperature by 0.5 degrees C in 14 days compared to placebo, while a 2 mM mixture significantly increased skin temperature by 0.3 degrees C in 7 days (P < or = 0.05; ANOVA). A single application of a 2 mM BMTd mixture applied 30 min before a 30 min cold challenge (6 degrees C), maintained facial skin temperature 1.4 degrees C above untreated control sites (P < or = 0.05; ANOVA). We also tested whether BMTd treatment would benefit people with dark circles under their eyes. Twenty-six panelists with dark undereye circles completed 2-week, twice daily application of a lotion containing the 1mM mixture to one eye while the other eye was untreated. Seven of 26 subjects showed a reduction of darkness of undereye circles (P < or = 0.05; paired t test). Application of 2 mM BMTd lotion to lips resulted in a significant increase in their redness, as measured by the erythema index (P < or = 0.05; ANOVA). These results show that a mixture of BMTd's increases nitric oxide, and application to skin increases microcirculation and skin temperature.

Boranes↗

PubMed2005

Acute effects of N-acetylcysteine on skeletal muscle microcirculation following closed soft tissue trauma in rats.

Trauma-induced microcirculatory dysfunction, formation of free radicals and decreased endothelial release of nitric oxide (NO) contribute to evolving tissue damage following skeletal muscle injury. Administration of N-acetylcysteine (NAC) known to scavenge free radicals and generate NO is considered a valuable therapeutic approach. Thus, the objective of this study was to quantitatively analyze the acute effects of NAC on skeletal muscle microcirculation and leukocyte-endothelial cell interaction following severe standardized closed soft tissue injury (CSTI). Severe CSTI was induced in the hindlimbs of 14 male anesthetized Sprague-Dawley rats using the controlled impact injury technique. Rats were randomly assigned (n = 7) to high-dose intravenous infusion of NAC (400 mg/kg body weight) or isovolemic normal saline (NS). Non-injured, sham-operated animals (n = 7) were subjected to the same surgical procedures but did not receive any additional fluid. Creatin kinase (CK) activity was assessed at baseline, 1 h before and 2 h following posttraumatic NAC or NS infusion. Microcirculation of the extensor digitorum longus (EDL) muscle was analyzed using intravital microscopy and Laser-Doppler flowmetry (LDF). Edema index (EI) was calculated by measuring the EDL wet-to-dry weight ratio (EI=injured/contralateral limb). EDL-muscles were analyzed for desmin immunoreactivity and granulocyte infiltration. Microvascular deteriorations observed following NS-infusion were effectively reversed by NAC: Functional capillary density was restored to levels found in sham-operated animals and leukocyte adherence was significantly (p < 0.05) reduced compared to the NS group. NAC significantly (p < 0.05) increased erythrocyte flux determined by Laser-Doppler flowmetry. Posttraumatic serum CK levels and EI were significantly (p < 0.05) decreased by NAC. During the posttraumatic acute phase, single infusion of NAC markedly reduced posttraumatic microvascular dysfunction, attenuated both leukocyte adherence and tissue infiltration. NAC also decreased CSTI-induced edema formation and myonecrosis as reflected by attenuated serum CK levels and attenuated loss of desmin immunoreactivity. NAC may serve as an effective therapeutic strategy by supporting microvascular blood supply and tissue viability in the early posttraumatic period. Additional studies aimed at long-term analysis and investigation of injury severity--or dosage dependency are needed.

Acetylcysteine↗

PubMed2004

Effect of tacrolimus and cyclosporine on renal microcirculation and nitric oxide production.

OBJECTIVES: Cyclosporine (CSA) and tacrolimus (TAC) frequently induce nephrotoxicity and similar pathologic changes. Acute CSA-induced nephrotoxicity has been reported to be mediated by activation of vasoconstrictors such as endothelin. The purpose of the present study was to investigate the acute effects of TAC and CSA on the renal microcirculation and upon a vasodilator such as nitric oxide (NO) production. METHODS: Renal blood flow (RBF) in the microcirculation was measured by a Laser Doppler flow meter in uninephrectomised rats. RBF, mean arterial pressure (MAP), and renal vascular resistance (RVR) were measured in the following groups: (a) TAC (0.1 to 2.0 mg/kg/h, n = 3 approximately 6); CSA (20 and 50 mg/kg/h, n = 5); (b) L-NAME (10 mg/kg), an NO synthase inhibitor, 8 minutes prior to TAC (0.5 and 1.5 mg/kg/h, n = 5), or CSA (20 and 50 mg/kg/h, n = 5). Stable NO end-products, serum NO(2) and NO(3), were measured by the Griess method (n = 5). RESULTS: None of the parameters were changed by TAC alone, whereas TAC with L-NAME significantly reduced RBF (-28 +/- 7%) and increased RVR (46 +/- 17%) in a dose-dependent manner. CSA alone significantly reduced RBF (-37 +/- 6%) and increased RVR (69 +/- 22%) without any changes in MAP. The effects of CSA were enhanced by L-NAME. Serum concentration of NO(2) + NO(3) was significantly reduced by both L-NAME alone and CSA (50 mg/kg) (P < .05), while there were no changes with TAC (1.5 mg/kg). CONCLUSIONS: Blockade of NO production enhance the vasoconstrictive effect of CSA, and unmasked such an effect of TAC. These results suggest that the nephrotoxicity of CSA and TAC may involve the NO system.

Animals↗

PubMed2005

FK506 donor pretreatment improves intestinal graft microcirculation and morphology by concurrent inhibition of early NF-kappaB activation and augmented HSP72 synthesis.

FK506 protects against ischemia-reperfusion injury but the mechanisms remain unclear. We investigated the impact of donor pretreatment using FK506 on graft microcirculation and morphology after intestinal transplantation. FK506 was given intravenously to SD rats (0.3 mg/kg) 6 hours before graft harvesting while controls received saline (n = 7/group). Grafts were stored for 3 hours in saline, then transplanted. Preservation induced similar lesions in both groups, but pretreated grafts showed better morphology than controls at 20 minutes after reperfusion. Six hours post-reperfusion, preconditioned grafts revealed near-normal morphology, whereas controls showed short villi, denuded areas, and intense inflammation. Pretreated grafts displayed a lower apoptotic rate and reduced caspase-3 activity. Hsp72 expression was enhanced in preconditioned grafts at harvesting, after preservation, and 20 minutes post-reperfusion compared to controls. Control grafts showed intranuclear p65 (activation of NFkappaB) at 20 minutes post-reperfusion; whereas pretreated grafts displayed no intranuclear p65. However, at 6 hours, comparable intranuclear p65 levels were found in both groups. ICAM-1 was low in both groups after preservation and early post-reperfusion, but greatly increased in controls at 6 hours post-reperfusion. In contrast, pretreated grafts continued to lack ICAM-1. Microvascular perfusion was comparable at 20 minutes. Six hours later, pretreated grafts had 30% increased perfusion, while in controls it was slightly decreased. FK506 alleviated reperfusion injury by blocking NF-kappaB activation and ICAM-1 transcription, thus decreasing endothelial activation and improving the microcirculation. It also induces Hsp72, therefore inhibiting apoptosis and accelerating morphologic restoration.

Animals↗

PubMed2006

Intravital microscopy of pulmonary microcirculation after single lung transplantation in pigs.

BACKGROUND: Pulmonary reperfusion injury is a significant risk factor following lung transplantation (LTx). Unfortunately, in vivo observations and quantitative analyses of the pulmonary microcirculation following LTx are technically demanding. METHODS: Pigs, weighing 18 to 22 kg, served as the laboratory animals. The left lung was harvested and preserved using donor aortic vessel segments, the pulmonary artery, and the cuff of the lung veins were extended. After 4 hours of ischemia, the lungs were transplanted by direct connection of the conduits to the left atrial appendage and the left pulmonary artery of the recipient. The lungs were placed extrathoracically and ventilated. The recipient left lung was excluded. With this procedure, mechanical trauma to the lung and moving artefacts were avoided. Intravital microscopic observation became feasible. RESULTS: Following reperfusion, oxygenation of pulmonary venous blood was excellent. However, blood flow distribution was significantly reduced to the transplanted lung compared with the native right recipient lung. Pulmonary vascular resistance was significantly increased, dropping from 3500 to 1000 dynes x s x cm(-5) during reperfusion compared to a value of 500 for the native right lung. The pulmonary microcirculation showed a significant number of no-reflow areas with extremely reduced red blood cell velocities. Greater than 90% of microvessels (<30 microm) showed velocities below 0.1 mm/sec. In conclusion, microvascular injury seems to be a major pathogenic factor for the development reperfusion failure. Quantification of alterations within the microvasculature may shed light on various treatment modalities that reduce perfusion failure.

Animals↗

PubMed1998

Microcirculation architecture of metastases from primary ciliary body and choroidal melanomas.

PURPOSE: To describe the microcirculation architecture of metastatic choroidal and ciliary body melanoma. METHOD: Histologic sections of 35 metastases from 19 primary melanomas were stained to demonstrate microcirculation. RESULT: The appearance of microcirculatory networks in metastases is independent of the target organ but associated with the size of the metastatic deposit (estimated coefficient = 0.5959; SE = 0.3024; P = .0488). CONCLUSION: The microcirculatory patterns of primary uveal melanomas that are associated with metastatic behavior appear in foci of metastasis, regardless of the site of dissemination.

Choroid Neoplasms↗

PubMed2003

Arrest of B16 melanoma cells in the mouse pulmonary microcirculation induces endothelial nitric oxide synthase-dependent nitric oxide release that is cytotoxic to the tumor cells.

Metastatic cancer cells seed the lung via blood vessels. Because endothelial cells generate nitric oxide (NO) in response to shear stress, we postulated that the arrest of cancer cells in the pulmonary microcirculation causes the release of NO in the lung. After intravenous injection of B16F1 melanoma cells, pulmonary NO increased sevenfold throughout 20 minutes and approached basal levels by 4 hours. NO induction was blocked by N(G)-nitro-L-arginine methyl ester (L-NAME) and was not observed in endothelial nitric oxide synthase (eNOS)-deficient mice. NO production, visualized ex vivo with the fluorescent NO probe diaminofluorescein diacetate, increased rapidly at the site of tumor cell arrest, and continued to increase throughout 20 minutes. Arrested tumor cells underwent apoptosis with apoptotic counts more than threefold over baseline at 8 and 48 hours. Neither the NO signals nor increased apoptosis were seen in eNOS knockout mice or mice pretreated with L-NAME. At 48 hours, 83% of the arrested cells had cleared from the lungs of wild-type mice but only approximately 55% of the cells cleared from eNOS-deficient or L-NAME pretreated mice. eNOS knockout and L-NAME-treated mice had twofold to fivefold more metastases than wild-type mice, measured by the number of surface nodules or by histomorphometry. We conclude that tumor cell arrest in the pulmonary microcirculation induces eNOS-dependent NO release by the endothelium adjacent to the arrested tumor cells and that NO is one factor that causes tumor cell apoptosis, clearance from the lung, and inhibition of metastasis.

Animals↗

PubMed2002

Hepatic dysfunction after left ventricular mechanical assist in patients with end-stage heart failure: role of inflammatory response and hepatic microcirculation.

BACKGROUND: In the condition of preexisting vital organ failure induced by heart failure, hepatic failure often progresses despite establishment of adequate hemodynamic support through a left ventricular assist device (LVAD) and results in a high mortality rate. We hypothesized that inflammatory responses, including those induced by infection and their influence on organ perfusion, may contribute to the pathogenesis of this progressive hepatic failure and subsequent multiple organ failure as reported in the current investigation on multiple organ failure after major surgery or trauma. METHODS: Hepatic function and its relation to inflammatory response and hepatic microcirculation were evaluated in 16 consecutive patients who received an implantation of LVAD for end-stage cardiomyopathy, between 1992 and 2000. Patients were divided into two groups: 5 patients who died from multiple organ failure after severe hepatic failure (group 1) and 11 patients who did not develop severe hepatic failure (group 2). Serum levels of CRP, interleukin (IL)-6, IL-8, and serum hyaluronan, a known indicator of hepatic sinusoidal function, were measured pre- and postoperatively in both groups. RESULTS: Serum ALT and AST levels during LVAD support were similar in the two groups. Serum total bilirubin (T-Bil), CRP, IL-6, and IL-8 levels before and during the first 20 days of LVAD support were significantly higher in group 1 than those in group 2 (p < 0.01 to 0.05). Serum hyaluronan levels in both groups were significantly correlated with T-Bil levels (r = 0.60, p < 0.05 in group 1; r = 0.68, p < 0.0001 in group 2). Histopathological examination by transvenous liver biopsy in a group 1 patient showed hepatic sinusoidal damage as well as cholestasis and fibrosis. CONCLUSIONS: Patients with hyperbilirubinemia and inflammatory reactions before LVAD support showed increased hyperbilirubinemia and inflammatory cytokine and hyarulonan levels despite adequate hemodynamics achieved under LVAD support. These results suggest that inflammatory response contributes to subsequent aggravation of hepatic dysfunction, probably with underlying and continuing derangement in hepatic sinusoidal microcirculation even under systemic circulatory support.

Adult↗

PubMed2002

Expression of PTHrP and its cognate receptor in the rheumatoid synovial microcirculation.

Parathyroid hormone-related protein (PTHrP), a multifunctional peptide that acts as a vasodilator as well as possible regulator of vascular development, is produced in increased amounts in the rheumatoid synovium. To understand whether PTHrP can contribute to the development and function of the rheumatoid microcirculation, studies were undertaken to identify and compare vascular sites of expression of PTHrP and its cognate receptor in the rheumatoid synovium and/or in cultured rheumatoid synovial endothelial cells. Endothelial cells, including apoptotic cells, as determined by TUNEL staining, were the primary site of vascular PTHrP expression in the rheumatoid synovium, a result confirmed in vitro in rheumatoid synovial microvascular endothelial cells. In contrast, the PTH/PTHrP receptor was primarily located in pericytes and smooth muscle cells within the vasculature. These results are consistent with a possible paracrine pathway for PTHrP action in the synovial microcirculation, wherein PTHrP peptides secreted by the synovial endothelium could act on surrounding PTH1R-positive pericytes and smooth muscle cells.

Arthritis, Rheumatoid↗

PubMed1992

Acetylcholine induces vasoconstriction in the microcirculation of cardiomyopathic hamsters: reversal by L-arginine.

The goal of this study was to determine whether endothelium-dependent responses of the microcirculation are altered during cardiomyopathy. We examined in vivo responses of cheek pouch arterioles to an endothelium-dependent agonist (acetylcholine) and an endothelium-independent agonist (nitroglycerin) in normal and in cardiomyopathic hamsters. In normal hamsters, acetylcholine produced dose-related dilatation of arterioles. In contrast, acetylcholine produced constriction of arterioles in cardiomyopathic hamsters. Nitroglycerin produced similar dose-related dilatation in normal and cardiomyopathic hamsters. We also examined whether impaired responses to acetylcholine in cardiomyopathic hamsters were related to an alteration in the L-arginine/nitric oxide pathway. We found that L-arginine (100 microM) restored endothelium-dependent vasodilatation to acetylcholine in cardiomyopathic hamsters. Thus, cardiomyopathy impairs endothelium-dependent responses of the microcirculation which is reversed by L-arginine.

Acetylcholine↗

PubMed1997

Effects of positive pressure on both femoral venous and arterial blood velocities and the cutaneous microcirculation of the forefoot.

OBJECTIVE: The balance between the apparent beneficial effect and the risk of arterial ischaemia resulting from an external uniform compression is unclear. The purpose of this study was to determine the effects of a positive uniform compression on the lower limb circulation until a critical threshold was reached. METHODS: We used Doppler ultrasound to measure femoral venous and arterial blood velocities. The effects of positive pressure on cutaneous microcirculation were evaluated by laser Doppler flux (LDF), transcutaneous oxygen pressure (tcpO2) and transcutaneous carbon dioxide pressure (tcpCO2) on the forefoot of 17 healthy subjects. RESULTS: The results are expressed as median [lowest observed value-highest observed value]. Whereas the arterial femoral velocity (A.F.V.) decreased from 0.21 [0.08-0.36] to 0.17 [0.08-0.28] m s-1 for an external pressure as low as 10 mmHg (p < 0.001), the venous femoral velocity (V.F.V.) decreased from 0.13 [0.06-0.40] to 0.09 [0.05-0.34] m s-1 at 20 mmHg (p < 0.001). An increase of tcpCO2 from 39.8 [29.9-53.7] to 40.2 [30.0-55.5] mmHg (p < 0.05) and a decrease of LDF from 8.7 [3.1-25.9] to 5.5 [2.3-21.1] A.U. (p < 0.001) occurred at 10 mmHg. However, tcpO2 decreased only from 76.7 [40.2-91.2] to 64.6 [18.9-85.2] mmHg when the splint pressure reached 60 mmHg (p < 0.05). The observed parameters (LDF, tcpO2, V.F.V. and A.F.V.) decreased further (except for tcpCO2 which increased) up to the end of the study as the applied pressure was increased. CONCLUSION: Positive pressure on the full leg provided no significant beneficial effect on femoral venous blood velocity. Whereas we showed that for an external uniform pressure as low as 10 mmHg, significant impairments in both arterial inflow of the lower limb and microcirculation of the forefoot appeared in recumbent healthy young subjects.

Adult↗

PubMed2001

Melatonin and N-acetylserotonin inhibit leukocyte rolling and adhesion to rat microcirculation.

The hormone melatonin produced by the pineal gland during the daily dark phase regulates a variety of biological processes in mammals. The aim of this study was to determine the effect of melatonin and its precursor N-acetylserotonin on the microcirculation during acute inflammation. Arteriolar diameter, blood flow rate, leukocyte rolling and adhesion were measured in the rat microcirculation in situ by intravital microscopy. Melatonin alone or together with noradrenaline did not affect the arteriolar diameter or blood flow rate. Melatonin inhibited both leukocyte rolling and leukotriene B(4) induced adhesion while its precursor N-acetylserotonin inhibits only leukocyte adhesion. The rank order of potency of agonists and antagonist receptor selective ligands suggested that the activation of MT(2) and MT(3) melatonin binding sites receptors modulate leukocyte rolling and adhesion, respectively. The effect of melatonin and N-acetylserotonin herein described were observed with concentrations in the range of the nocturnal surge, providing the first evidence for a possible physiological role of these hormones in acute inflammation.

Animals↗

PubMed1998

L-arginine and NG-nitro-L-arginine methyl ester cause macromolecule extravasation in the microcirculation of awake hamsters.

We investigated the effects of L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) on macromolecule extravasation in the microcirculation of awake hamsters by computer-assisted image analysis of the distribution of FITC (fluorescein isothiocyanate)-dextran fluorescence in dorsal fold skin preparations. This analysis made it possible to simultaneously study the time course of local (skin) and general (all irrigated organs) extravasation in 180-min experiments. Bolus injection of 30 or 150 mg/kg (i.v.) L-arginine induced immediate local and general macromolecule leakage and delayed venule dilation beginning 1 h later. Injection of 20 or 100 mg/kg (i.v.) L-NAME caused rapid venule constriction followed by local and general extravasation beginning 45-60 min later. These effects of L-arginine and L-NAME were not mimicked by their biologically inactive isomers, D-arginine and D-NAME. Simultaneous bolus injection of 20 mg/kg L-NAME and 150 mg/kg L-arginine caused no significant change in fluorescence distribution or venule diameter. L-arginine effects on macromolecule extravasation were mimicked by sodium nitroprusside (10 microg/kg, i.v.) and by 8-bromo-cGMP (1 mg/kg, i.v.). Sodium nitroprusside was ineffective on venule diameter. The effects of both L-arginine and sodium nitroprusside on FITC-dextran extravasation were prevented by simultaneous injection (10 microg/kg, i.v.) of the specific inhibitor of the soluble guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). This dose of ODQ mimicked the effects of L-NAME on macromolecule extravasation and venule diameter. Taken together, these results suggest that activation or inhibition of basal NO synthesis might induce macromolecule leakage in the microcirculation of awake hamsters via temporally distinct cGMP-dependent mechanisms.

Animals↗

PubMedDate not supplied

Effects of caffeine on microcirculation of the human ocular fundus.

PURPOSE: To determine the effect of caffeine on microcirculation in the human ocular fundus. METHODS: The microcirculation in the ocular fundus of 10 healthy volunteers (10 eyes) was studied using a laser speckle tissue circulation analyzer. Caffeine or placebo (100 mg) was administered orally in a double-masked manner. Square blur rate (SBR), a quantitative index of blood flow velocity, was measured in a temporal site of the optic nerve head (ONH) free of surface vessels and in a middle site of the choroid-retina between the ONH and macula. Intraocular pressure (IOP), blood pressure (BP), pulse rate (PR), and central critical fusion frequency (CFF) were also measured. These parameters were measured before and for 2 hours after administration. The area under curve (AUC) of SBR was calculated for each area. Ocular perfusion pressure (OPP) was also calculated from BP and IOP. RESULTS: The time-course of change in SBR value showed much individual difference. Caffeine decreased the AUC of SBR in the ONH (P =.0218) as well as in the choroid-retina (P =.0469) significantly. IOP, mean BP, PR, OPP, and central CFF did not change significantly. CONCLUSIONS: These results suggest that caffeine may increase blood vessel resistance and decrease blood flow in the human ONH and choroid-retina.

Adult↗