Microcirculation in obesity: an unexplored domain

Obesity is traditionally linked to diabetes and cardiovascular diseases. Very recent experimental, clinical and epidemiological, sometimes provocative, data challenge this automaticity by showing that not the amount but the distribution of fat is the important determinant. Moderate abdominal fat accumulation may thus be more harmful than even consequent overweight. In view of the worldwide burden of obesity, factors leading to it in children and young adults must urgently be identified. Since obesity is a very complex cardiometabolic situation, this will require to focus investigations on uncomplicated obese subjects and adequate animal models. The recent discovery of intergenerational transmissions of obesity risk factors and also the key role played by gestational and perinatal events (epigenetic factors) give rise to completely new concepts and research avenues. Considering the potential close relationship between microcirculation and tissue metabolism, demonstrations of structural and/or functional abnormalities in microvascular physiology very early in life of subjects at risk for obesity might provide a solid basis for further investigations of such links. Microcirculation(arterioles, capillaries and venules) is conceivably a key compartment determining over one or several decades the translation of genetic and epigenetic factors into fat accumulation. Available animal models should serve to answer this cardinal question.

A obesidade é tradicionalmente associada ao diabetes e adoenças cardiovasculares. Dados muito recentes, algumasvezes provocativos, experimentais, clínicos e epidemiológicos questionam essa associação automática mostrando que não é a quantidade, mas a distribuição de gordura que é o determinante importante. O acúmulo moderado de gordura abdominal pode ser mais danoso que o conseqüente sobrepeso. Tendo em vista o aumento mundial da obesidade, fatores que levam a isso em crianças e adultos jovens devem ser urgentemente identificados. Como a obesidade é uma situação cardiometabólica muito complexa, essa identificação deve ser feita em obesos não-complicados e em modelos animais adequados. A recente descoberta da transmissão inter-geração de fatores de risco da obesidade e também do papel fundamental da gestação e de eventos perinatais (fatores epi-genéticos) dão origem a conceitos e linhas de pesquisa completamente novos. Considerando a estreita relação potencial entre a microcirculação e o metabolismo tecidual, demonstrações de anormalidades estruturais e/ou funcionais na fisiologia microvascular muito cedo na vida de pessoas com risco para obesidade podem fornecer uma base sólida para investigações futuras dessas ligações. A microcirculação (arteríolas, capilares e vênulas) é conceitualmente um compartimento chave na determinação em uma ou várias décadas dos fatores genéticos e epi-genéticos em acúmulo de gordura. Os modelos experimentais disponíveis devem servir para responder essa questão extremamente relevante.

Role of Ca++ gradient in functional dilatation in the microvessels of rat skeletal muscle.

During skeletal muscle contraction functional dilatation (FD) is a well established phenomenon, which is usually linked to the accumulation of various vasodilator metabolites. The present study aimed to establish the role of calcium ions (Ca++) in the functional dilatation of skeletal muscle microvessels especially during single & few twitches. The FD was studied in urethane anaesthetized rats whose spinotrapezius muscle was prepared for intravital microscopy. After stimulating the muscle with few twitch (1 & 3 Hz) and tetanic frequency (40 Hz), muscle contracted and showed dilatation. However the dilator response was quickest (1 Hz : 10 +/- 0.40, 3 Hz : 02 +/- 0.47 sec and 40 Hz : 02 +/- 0.10 sec) and maximum in magnitude (1 Hz : 25 +/- 0.30%, 3 Hz : 35 +/- 0.49% and 40 Hz : 55 +/- 0.39%) in terminal arteriole and with tetanic frequency. Calcium channel blockade by Diltiazem abolished the FD response except for tetanic stimulation contraction. Findings suggested possible involvement of Ca++ movement in functional dilatation which was initiated by passive efflux of Ca++ from smooth muscle of vessel and then maintained during higher frequency stimulation by release of local metabolities.

Determination of macromolecular exchange and PO2 in the microcirculation: a simple system for in vivo fluorescence and phosphorescence videomicroscopy

We have developed a system with two epi-illumination sources, a DC-regulated lamp for transillumination and mechanical switches for rapid shift of illumination and detection of defined areas (250-750 æm²) by fluorescence and phosphorescence videomicroscopy. The system permits investigation of standard microvascular parameters, vascular permeability as well as intra- and extravascular PO2 by phosphorescence quenching of Pd-meso-tetra (4-carboxyphenyl) porphine (PORPH). A Pechan prism was used to position a defined region over the photomultiplier and TV camera. In order to validate the system for in vivo use, in vitro tests were performed with probes at concentrations that can be found in microvascular studies. Extensive in vitro evaluations were performed by filling glass capillaries with solutions of various concentrations of FITC-dextran (diluted in blood and in saline) mixed with different amounts of PORPH. Fluorescence intensity and phosphorescence decay were determined for each mixture. FITC-dextran solutions without PORPH and PORPH solutions without FITC-dextran were used as references. Phosphorescence decay curves were relatively unaffected by the presence of FITC-dextran at all concentrations tested (0.1 æg/ml to 5 mg/ml). Likewise, fluorescence determinations were performed in the presence of PORPH (0.05 to 0.5 mg/ml). The system was successfully used to study macromolecular extravasation and PO2 in the rat mesentery circulation under controlled conditions and during ischemia-reperfusion

Glucose transport in cerebral microvessels during Plasmodium yoelii nigeriensis infection in mice.

Plasmodium yoelii infected cerebral micro vessels of mice registered a significant increase in D-[U-14C] Glucose transport as compared to normal microvessels which was found to be time, temperature and concentration dependent. Metabolic inhibitors galactose, manose, 2-deoxy glucose and D-glucose showed noticeable inhibition of the same.