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[Acute effects of topical application of methyl N-trimethyl-gamma-aminobutyrate chloride on cutaneous microcirculation in the healthy male rabbit].

Effects of acetylcholine (ACh) and its reversed carboxy analogue, methyl N-trimethyl-gamma-aminobutyrate chloride (MTB), induced either by topical application to the skin surface around a transparent round table chamber (REC) that had been previously installed to the ear lobe or by intravenous injection on the micro- and macrocirculations were studied in the healthy male rabbit. The effects of both drugs on the cutaneous microcirculation within the REC were observed vital-microscopically under conscious conditions and the microcirculatory events were visualized with a microscope-closed TV system and microphotoelectric plethysmography. The results were as follows: (1) Topical application of 1% MTB cream caused an enhanced perfusion of rhythmic microvascular blood due to vasomotion for a period of 30 min or longer, while ACh did so to a much less extent, if any. On the other hand, no appreciable change developed in any systemic hemodynamic parameters. (2) Intravenous administration of MTB or ACh caused a very transient dilator effect on micro-and macrocirculatory blood vessels according to its cholinergic stimulation, which could be blocked by atropinization. Almost the same efficacy on vasomotion was observed for each drug. (3) These findings indicate that the topical application of MTB to the skin surface may cause a physiologically acceptable vasodilation accompanied by vasomotion, and it would facilitate the oxygen diffusion by the follicular circulation.

Acetylcholine↗

Optical bioimaging: from living tissue to a single molecule: imaging and functional analysis of blood flow in organic microcirculation.

Activity of blood cells, erythrocytes, leucocytes, and platelets, in microcirculation was observed by using an intravital microscope and confocal laser scanning microscope connected with an image processing system including fluorescence and phosphorescence emission methods. Dynamic functions of the blood flow were mainly observed in mesentery, brain, and liver tissues of rats. The results are summarized as follows: Deformability of diabetic erythrocytes was significantly lower than that of healthy controls, particularly at high shear rate. The spring constant and Young's modulus of diabetic erythrocytes obviously stiffened, making them hard to deform in the capillary. During hemorrhagic shock and thrombosis, flow velocity and oxygen partial pressure of blood decreased in the brain and liver tissues that can be visualized by using FITC stained erythrocytes and Pd-porphyrin derivative as a pO(2) probe. Platelet adhesion and thrombus formation in the micro-vessels accelerated under the photodynamic reaction; diabetic platelets showed augmented adhesion and aggregation on the vessel wall which was followed by acute thromboembolism. Active oxygen radicals take part in thrombus formation, accompanied with adhesion of the activated leucocytes. Fluorescent dye probes, rhodamine G and acridine orange, are quite useful for visualization of the flow behavior of platelets and leucocytes, respectively.

Animals↗

Laryngeal microcirculation and pathways of cancer spread.

The microcirculation of the human larynx was studied in cleared anatomic specimens. The distribution of the endolaryngeal blood supply was constant enough to permit naming of the subdivisions of the superior and inferior laryngeal arteries. There was a remarkable correlation between arteriolar and capillary distribution and the laryngeal routes of cancer spread within the larynx. Compartmentalization of the larynx was not apparent. The paraglottic space was filled with blood vessels.

Adult↗

Disparate effects of calcium antagonists on renal microcirculation.

Although calcium antagonists reduce systemic blood pressure, the effects of calcium antagonists on renal preglomerular and postglomerular microcirculation have been suggested to differ. In the present study we examined the vasodilator action of dihydropyridine-type calcium antagonists, including nifedipine, nicardipine, amlodipine, and efonidipine, on afferent and efferent arterioles during angiotensin II (A-II)- and norepinephrine (NE)-induced renal vasoconstriction. Isolated perfused hydronephrotic kidneys were used to directly visualize renal microcirculatory response to calcium antagonists. Both A-II and NE caused marked vasoconstriction of afferent (A-II, 27 +/- 2% decrement; NE, 28 +/- 2% decrement) and efferent arterioles (A-II, 25 +/- 4% decrement; NE, 22 +/- 2% decrement). The subsequent addition of nifedipine, nicardipine, and amlodipine reversed the afferent arteriolar vasoconstriction in a dose-dependent manner, and elicited complete vasodilation at 10(-6) M. In contrast, efferent arteriolar vasoconstriction was relatively refractory to the dilator action of these calcium antagonists; maximal dilation observed at 10(-6) M was 21 +/- 1% (A-II) and 22 +/- 3% (NE) for nifedipine, 25 +/- 3% (A-II) and 20 +/- 6% (NE) for nicardipine, and 39 +/- 6% (A-II) and 37 +/- 3% (NE) for amlodipine. In striking contrast, efonidipine dilated not only afferent arterioles, but also efferent arterioles in a dose-dependent manner. At 10(-6) M, efonidipine completely inhibited the afferent (A-II, 89 +/- 7% reversal; NE, 99 +/- 8% reversal) and efferent arteriolar vasoconstriction (A-II, 93 +/- 4% reversal; NE, 87 +/- 9% reversal). These findings clearly demonstrate that calcium antagonists dilate the afferent arteriole. Unlike the effects on the afferent arteriole, efferent arteriolar responsiveness to calcium antagonists differ, depending on the type of calcium antagonist. The efonidipine-induced efferent arteriolar vasodilation is probably not related to voltageoperated calcium channels, and may act, in concert with blood pressure lowering effect, to ameliorate glomerular capillary hypertension.

Angiotensin II↗

Effects of a nucleoside transporter inhibitor, dilazep, on renal microcirculation in rats.

Adenosine, one of the endogenous modulators in renal hemodynamics, has recently been shown to be a mediator of tubuloglomerular feedback (TGF). Dilazep augments endogenous adenosine actions by blocking its cellular uptake. Our purpose in the present study was to clarify the effects of dilazep on renal microcirculation and the TGF mechanism. Clearance and micropuncture experiments were performed in anesthetized rats. TGF responsiveness was assessed in superficial nephrons by measuring the changes of early proximal flow rate (EPFR) in response to loop perfusion at 0-40 nl/min with artificial tubular fluid (ATF). Under dilazep administration (0.3 mg/kg+0.3 mg/kg/h i.v.) systemic BP and GFR were decreased and renal plasma flow was unaltered; as a result, the filtration fraction tended to decrease (p=0.076). Renal vascular resistance was reduced, but not to a significant degree. The reduction in EPFR by loop perfusion was similar between controls (47 +/- 2%) and rats administered dilazep i.v. (44 +/- 5%). Intraluminal application of dilazep in ATF suppressed TGF-mediated EPFR reduction to by 46 +/- 4%, 43 +/- 7%, and 37 +/- 3% at dilazep concentrations of 10(-6), 10(-5), and 10(-4) mol/l, respectively. TGF suppression with 10(-4) mol/l dilazep was reversed by co-perfusion of 10(-5) mol/l DMPX, a selective adenosine A2 receptor antagonist. DMPX alone did not affect TGF response. In conclusion, these results indicate that systemic dilazep dilates postglomerular arterioles and does not affect TGF, and thus reduces GFR. A pharmacological concentration of dilazep applied to single nephrons clearly attenuates TGF, indicating afferent arteriolar vasodilatation. Extracellular adenosine augmented by dilazep dilates glomerular vessels at both afferent and efferent sites, probably via the activation of A2 receptors.

Animals↗

Control of oxygen uptake, microcirculation and glucose release by circulating noradrenaline in perfused rat liver.

The effect of noradrenaline on oxygen uptake, on periportal and perivenous oxygen tension at surface acini, on microcirculation and on glucose output were studied in isolated rat livers perfused at constant flow with Krebs-Henseleit-hydrogen carbonate buffer containing 5mM glucose and 2mM lactate. Noradrenaline at 1 microM concentration caused a decrease in oxygen uptake, while at 0.1 microM it led to an increase. Both high and low doses of noradrenaline decreased the tissue surface oxygen tension in periportal and - after a transient rise - in perivenous areas. Noradrenaline at an overall constant flow caused an increase of portal pressure and an alteration of the intrahepatic distribution of the perfusate: at the surface of the liver and in cross sections infused trypan blue led to only a slightly heterogeneous staining after a low dose of noradrenaline but to a clearly heterogeneous staining after a high dose. Both high and low doses of noradrenaline stimulated glucose release. All effects could be inhibited by the alpha-blocking agent phentolamine. In conclusion, control of hepatic oxygen consumption by circulating noradrenaline is a complex result of opposing hemodynamic and metabolic components: the microcirculatory changes inhibit oxygen uptake; they dominate after high catecholamine doses. The metabolic effects include a stimulation of oxygen utilization; they prevail at low catecholamine levels. The noradrenergic control of glucose release is also very complex, involving direct, metabolic and indirect, hemodynamic components.

Animals↗

Laser Doppler flowmetry--peripheral microcirculation during cessation of cerebral and cardiocirculatory function.

Laser Doppler flowmetry (LDF) is a noninvasive method to study the microcirculation. We studied the feasibility of the clinical use of LDF in the intensive care unit by continuously recording different LDF parameters during the cessation of cerebral and cardiocirculatory function. The LDF-Conc (concentration of red blood cells) reflected biological phenomena correlated with the heart rate and microvibration that could not be detected with conventional means (systemic blood pressure, peripheral oxygen saturation).

Aged↗

Treatment of rats with hCG induces inflammation-like changes in the testicular microcirculation.

Adult rats were injected subcutaneously with 50 i.u. hCG and vascular permeability was compared to that in saline-treated control rats by two independent methods. At 4 h after hCG treatment the rats were injected intra-arterially (i.a.) with FITC-labelled macromolecular dextran (Mr 150,000) and the testicular microcirculation was studied in vivo by using a fluorescence microscope. Other rats were injected i.a. with a suspension of colloidal carbon and the location of leaking blood vessels was recorded in sections from the testes by light and electron microscopy. In hCG-treated animals leucocytes were found adhering to the endothelium in post-capillary venules and in these venular segments dextran was leaking into the interstitium. Carbon particles were deposited in the walls of post-capillary venules and leucocytes migrated through open interendothelial cell gaps in hCG-treated animals. In control animals leucocyte adhesion and migration were not observed, the injected dextran remained in the circulation and the blood vessels were not labelled by carbon. It is suggested that the hCG-induced increase in testicular interstitial fluid volume, like the tissue oedema in inflammation, is caused by a leucocyte-mediated increase in venular permeability.

Animals↗

Microcirculation and Chagas' disease: hypothesis and recent results.

This review focuses on studies that support the microvascular hypothesis, as well as on immunological and neurogenic mechanisms, and the role of the parasite itself, to explain further the pathology and clinical course of myocardial involvement in chagasic cardiomyopathy. The salient features of coronary microcirculation and Chagas' disease are discussed.

Animals↗

Obstructive sleep apnea and insulin resistance: a role for microcirculation?

Obstructive sleep apnea is an increasingly recognized medical problem. The recent attention to its frequency in the general population and its important role in metabolic, vascular, and behavioral aspects have sharply increased the number and nature of investigations, thereby revealing new aspects that open new approaches in research. Whereas obstructive sleep apnea is a well-known phenomenon accompanying obesity and diabetes, new findings strongly suggest that this close relationship may also operate in the opposite direction. Indeed obstructive sleep apnea may be a primary feature inducing or aggravating a series of vascular and metabolic disturbances closely resembling the metabolic syndrome. This review will discuss established and potential mechanisms responsible for these changes. Obstructive sleep apnea indeed appears to gather all the elements necessary to induce insulin resistance, hypertension, and possibly heart failure. After careful analysis of these modifications and considering how they are intertwined, we propose that microcirculation could represent the common denominator mediating the progression of this pathology, as it is eventually the case in the metabolic syndrome and diabetes domain. This plausible hypothesis is discussed in detail and should be verified by appropriate preclinical and clinical protocols, which are now achievable by using noninvasive techniques in humans.

Cardiovascular Diseases↗

Investigation of blood flow microcirculation by diffusing wave spectroscopy.

This article presents a technique and a setup for noninvasive in vivo studies of cutaneous microcirculation. The technique is based on the analysis of intensity fluctuations of scattered coherent light. The analysis is made in terms of diffusing wave spectroscopy. The developed technique can be used in clinical practice to determine the motion pattern of scattering particles (such as red blood cells) in randomly inhomogeneous media (such as biological tissues). The average size of scattering particles can be comparable to the wavelength of scattered radiation.

Animals↗

Ovariectomy improves neovascularization and microcirculation of freely transplanted ovarian follicles.

To investigate the influence of ovariectomy on the physiological process of neovascularization of ovarian follicles, we harvested follicles with a theca interna at 48 h after pregnant mare's serum gonadotropin (PMSG) treatment of Syrian golden hamsters, for subsequent transplantation onto striated muscle tissue of chronically implanted skinfold chambers of non-ovariectomized PMSG-synchronized hamsters and bilaterally ovariectomized hamsters. Non-ovariectomized non-PMSG-treated animals served as controls. During a 2 week period after transplantation, neovascularization of these freely transplanted grafts was quantified in vivo by assessment of the newly developed microvascular follicular network, its microvessel density, the diameter of microvessels and their volumetric blood flow using fluorescence microscopic techniques. At day 3 after transplantation, capillary sprouts could be observed in all groups studied, finally developing a complete glomerulum-like microvascular network within 5-10 days. In ovariectomized animals, however, vascularization of follicular tissue was found to be accelerated and enhanced when compared with the follicles in both groups of non-ovariectomized animals. This was associated with significantly higher capillary blood perfusion, which may in part represent the graft's adaptive response to pro-angiogenic stimuli due to elevated gonadotropin levels, but might in particular be mediated by gonadotropin-induced release of vasoactive substances. Interestingly, small preantral follicles lacking a theca interna failed to vascularize in either of the groups. In conclusion, the study demonstrates that ovariectomy improves neovascularization and microcirculation of freely transplanted ovarian follicles.

Analysis of Variance↗

Relationships between cell division, expression of growth factors and microcirculation in the thyroids of Tg-A2aR transgenic mice and patients with Graves' disease.

Tissue heterogeneity and nodule formation are hallmarks of thyroid growth. This is accounted for by the clonality theory that acknowledges different individual cellular abilities to respond to trophic stimuli. In order to test the hypothesis that functional and mitotic properties of thyrocytes could be influenced by paracrine interactions with neighbour endothelial cells, studies were conducted in both mouse and human goitre models. In the first part of the study, homogenous goitres in C57 black mice were compared with heterogeneous goitres in transgenic hyperthyroid mice expressing the A2 adenosine receptor (Tg-A2aR). The second part of the study concentrated on comparing human thyroid tIssue of control individuals and of patients with Graves' disease. The rate of cell division was evaluated by immunohistochemical detection of cells positive for proliferating cell nuclear antigen (PCNA). Their spatial distribution was then correlated with immunohistochemical cellular expression of growth- and vasoactive-related factors (fibroblast growth factor-2, transforming growth factor-beta, endothelin-1, vascular endothelial growth factor, nitric oxide synthase III), and with microcirculation expansion. Observations were made on digitalised images of histological serial sections. The nearest-neighbour method was used to distinguish between random or clustered distribution. PCNA-positive cells were both randomly and uniformly distributed in homogenous goitres from C57 black mice, and were clustered in tIssue areas identified as papillary and hyperplastic zones in heterogeneous goitres from Tg-A2aR mice. However, they were absent in the so-called compact cellular zones featuring resting cells. Moreover, whereas papillary and hyperplastic zones were highly vascularised, compact zones were nearly free of microvessels. Spatial distribution of dividing cells was positively correlated with the expression of growth-related factors. A similar pattern was observed in the thyroids of patients with Graves' disease. In accordance with the recent demonstration of the presence of angiofollicular units in the thyroid, these data strongly support the hypothesis that functional and mitotic properties of each single thyrocyte, likely to be responsible for growth heterogeneity of hyperplastic glands, may be adjusted at tIssue level by specific interactions with neighbour endothelial cells that, in turn, could alter the mitotic rate of thyrocytes through paracrine signals.

Animals↗

Microcirculation of the pancreas in the rat and rabbit with special reference to the insulo-acinar portal system and emissary vein of the islet.

Microcirculation of the pancreas in the rat and rabbit with special reference to the islets was studied by scanning electron microscopy (SEM) of vascular corrosion casts, light microscopy (LM) of India ink-injected/cleared tissues, and intravital microscopy of in situ organs. The following observations were made: Approximately 10-20% of the total terminal arterioles supplied the islets, while the remainder directly supplied the exocrine pancreas. The vas afferens of the islets divided into sinusoidal capillaries with frequent U-shaped turns in the cortical A and D cell area of the islets, and their secondary branches supplied the core B cell area. Intravital microscopy confirmed that blood irrigated the cortex of the islets first and the core portion second. All islets observed possessed insulo-acinar portal vessels. About 60% of the islets in the rat possessed emissary veins leading directly into the systemic circulation, while in the rabbit, less than 5% of islets possessed emissary venules of small diameter. Thus, the well-developed emissary veins of the islets seemed characteristic of the rat, as compared with the rabbit and several other mammals examined previously. The insulo-acinar portal system seems to represent a short vascular route through which islet secretions are transported in high concentrations to the exocrine pancreas, there to exert their actions. The emissary veins of the islet seem to serve for the quick conveyance of insular secretions into general circulation. It is suggested that the pancreatic lobule is made up of subdivisions or microcirculatory units, each of which is supplied centrally by the insulo-acinar portal system, while peripherally the unit also receives direct branches of intralobular arterioles. The veins run the periphery of the unit. The occurrence of sphincters in the vas afferens and the emissary veins of the islets is suggested as being involved in the regulation of the islet blood flow.

Animals↗

Microcirculation of the rat pancreas, with special reference to the insulo-acinar portal and insulo-venous drainage systems: a further scanning electron microscope study of corrosion casts.

Microcirculation in rat pancreas was studied by scanning electron microscopy of resin vascular casts and by light microscopy of India ink-injected and sectioned tissue samples. In the scanning survey of the casts, islets larger than 30 microns in diameter counted no less than 400 in the adult rat pancreas. They were located either in the exocrine lobules (intralobular islets, counting 210 or more), or in the interlobular tissue spaces and along the secretory ducts (extralobular islets, 190 or more). Every islet received arterial blood via one or more proper arterioles. These afferent vessels first divided in the peripheral zone of the islet consisting of A and D cells and later extended deeper to form a capillary network in the islet core consisting of B cells. Blood originating from this capillary network left the islet via efferent vessels. This microvascular pattern may favor the regulation by A and D cells over the secretory activity of B cells. The intralobular islets gave their efferent vessels to the capillary bed of the exocrine tissue of the lobule, thus forming an insulo-acinar portal system. When the lobule was relatively small in size, superfluent blood was led directly to veins via insulo-venous drainage vessels. The intralobular islets sometimes issued one or more long translobular portal vessels reaching adjacent lobules. The extralobular islets issued either insulovenous vessels draining to interlobular veins, or extralobular insulo-acinar portal vessels supplying adjacent lobules.

Animals↗

Microcirculation of the rat small intestine as studied by the injection replica scanning electron microscope method.

Mucosal blood supply in the rat small intestine was studied by the injection replica scanning electron microscope method. The blood vascular plexus in the villus is originated at the tip of the villus and confluenced near the base of the villus. This supports the classical "fountain pattern" of MALL in the villous microcirculation. The capillary plexus in the crypt is derived at the base of the crypt and converged near the base of the crypt. The capillary plexuses in the villus and the crypt communicate with each other. It is considered that the basal segment of the villus, where the arterial termination is lacking, is supplied by the cryptal capillaries via this communication.

Animals↗

Renal microcirculation of the bullfrog, Rana catesbeiana. A scanning electron microscope study of vascular casts.

The microcirculation of the bullfrog kidney was studied by scanning electron microscopy of the corrosion casts. The bullfrog kidney derives its blood supply from a dual origin: one is from the posterior half of the body via the renal portal veins and the dorso-lumbar veins, the other is from the urogenital arteries. The renal portal veins are linked with the hepatic portal system through the anterior abdominal vein which might serve as a transport route of the potentially renal portal blood to the kidney. The glomerulus consists of several lobules of anastomosing capillaries which are intercalated between the afferent and efferent arteriole. The efferent arteriole of the glomerulus runs some distance ventrad without branching to join the peritubular sinusoidal capillaries near the ventral surface of the kidney. Usually each glomerulus has a single efferent arteriole, but double efferent arterioles may rarely occur. Near the medial border of the kidney the glomeruli are small, and laterally they become progressively larger.

Animals↗