Microcirculation, endothelium, and lymphatics最新文献

Studies were performed to determine the vasomotor effects of leukotrienes, LTC4 and LTD4, on rat cremaster third-order arterioles and the effects of PGE2 on arteriolar responsiveness to LTC4. Five to six week-old male rats were anesthetized with sodium pentobarbital (35 mg/kg) and the left cremaster muscle exteriorized and prepared for in vivo television microscopy. Measurement of changes in arteriolar internal diameters was performed with an electronic image shearing device under control conditions and during the topical administration of vasoactive substances before and after the suffusion, onto the surface of the cremaster muscle, of either indomethacin (IND, 10 ug/ml) or 5,8,11,14-eicosatetraynoic acid (ETYA, 20 ug/ml). LTC4 and LTD4 were found to evoke equivalent, dose-dependent arteriolar constrictions, in the dose range of 2 pg to 2 ng, and concomitant decreases in microvascular blood flow. The application of either IND or ETYA, to the cremaster muscle did not significantly effect control diameters nor the constrictor responses to leukotrienes. While the principal action of the two leukotrienes was vasoconstriction, small dilator responses were occasionally observed that were also not affected by IND or ETYA. PGE2 did not inhibit the arteriolar constrictor responses to LTC4. The current observations indicate that LTC4 and LTD4 are extremely potent arteriolar constrictor agents in skeletal muscle and that their vascular effects are not mediated or modulated by products of the cyclooxygenase or lipoxygenase pathway of arachidonic acid metabolism.

The goal of this study was to determine if active tone and arteriolar constriction in response to increased PO2 are enhanced in the mesenteric microcirculation of spontaneously hypertensive rats (SHR) relative to normotensive Wistar-Kyoto (WKY) controls. Diameters of arterioles, metarterioles, and precapillary arterioles were measured in the mesoappendix of anesthetized 12-15 week old SHR and WKY rats during superfusion with physiological salt solution equilibrated with either 0%, O2, 5% O2 or 10% O2, with 5% CO2-balance N2. Active tone was assessed by superfusion with 10(-4) M adenosine. Metarterioles of SHR constricted significantly more than those of WKY when superfusion solution PO2 was elevated, but vessel closure did not occur in response to elevated PO2 in either SHR or WKY. Arteriolar dilation in response to 10(-4) M adenosine was not significantly different in hypertensive and normotensive animals, suggesting that resting tone is not elevated in mesoappendix arterioles of SHR. Although metarterioles of SHR constricted significantly more than those of WKY in response to elevated PO2, an enhanced response of arterioles to increased oxygen availability does not appear to contribute to functional rarefaction (i.e., active vessel closure) of small arterioles in the mesenteric microcirculation of SHR.

The ability of the purified stereoisomers of the beta 2-receptor agonist terbutaline to block bradykinin-mediated increases in lymph flow and protein concentration was assessed in the canine forelimb perfused at constant arterial flow. Intra-arterial infusion of bradykinin (2 micrograms/min, n = 8) decreased forelimb arterial pressures but did not affect skin small vein pressure or systemic pressure. Lymph flow, protein concentration and protein transport were significantly increased. Intra-arterial infusion of 1-terbutaline (1 microgram/min, n = 9) decreased forelimb arterial pressures and systemic pressure but did not affect lymph parameters. Subsequent infusion of bradykinin during the continued infusion of 1-terbutaline failed to alter forelimb lymph parameters. Intra-arterial infusion of d-terbutaline (1 microgram/min, n = 11) did not alter vascular pressures or lymph parameters. Subsequent infusion of bradykinin during the continued infusion of d-terbutaline decreased forelimb arterial pressures and significantly increased lymph flow, protein concentration and protein transport. Intra-arterial infusion of a high dose (100 micrograms/min, n = 9) of d-terbutaline significantly decreased forelimb arterial pressure but was likewise ineffective in blocking the increases in lymph parameters produced by subsequent bradykinin infusion. These data indicate that the beta 2-receptor agonistic and anti-permeability actions of terbutaline are found solely in the levorotatory enantiomer.

During the healing phase of a chemical peritonitis in rats, absorption of various inocula from the peritoneal cavity into the draining lymph nodes is increased. Heretofore, this phenomenon has been attributed to fibrosis and shrinkage of the greater omentum. The loss of the sequestering function of the omentum allows the inoculum more ready access to the lymphatic vessels in the diaphragm where it is absorbed. In the present work, it is demonstrated that the chemical peritonitis also widens the stomata in the roofs of the diaphragmatic lymphatic lacunes. Both increased access and larger openings contribute to enhanced lymphatic absorption in the postinflammatory state.

Circulating-blood glucose, hepatic glycogen distribution, and the glycogen contents of liver and skeletal muscle, were determined for 60 min in 31 fed and anesthetized Sprague-Dawley rats. These rats received an endoportal infusion of 15 mg per kg b.w. E. coli endotoxin (026:B6) or of sterile saline solution as a control. Either substance was given intravenously at 9:30 a.m. following an intraperitoneal injection at 9:00 a.m. of 0.1 mg per kg b.w. prazosin or 0.3 mg per kg b.w. yohimbine or of the carrier, distilled water. Infused endotoxin elevated blood glucose without affecting hepatic glycogen distribution and total glycogen contents of liver and skeletal muscle when compared to control. Prazosin inhibited endotoxin-induced hyperglycemia, and prazosin plus endotoxin provoked centrilobular glycogen depletion and decreased total hepatic glycogen content. However, no significant alteration in the glycogen content of skeletal muscle accompanied blockade of glucogenesis. Prazosin administered by itself produced no changes in hepatic and muscle glycogen. Although yohimbine blocked endotoxin-induced hyperglycemia, yohimbine, or yohimbine plus endotoxin, produced no significant change in the glycogen contents of liver and skeletal muscle. Blockade in the latter case was associated with some depletion of glycogen in hepatocytes dispersed randomly throughout the unit lobule and in cells located centrivenously. These results suggested that endotoxin-induced hyperglycemia is evoked by activation of alpha-1 and -2 adrenergic receptors. Since no detectible change in hepatic glycogen distribution and in the contents of liver and muscle glycogen accompanied glucogenesis, glycogen catabolism and deposition are postulated to proceed simultaneously and at equivalent rates by 60 min following the experimental induction of endotoxemia. Blockade of alpha (one or two) adrenoceptors is hypothesized to inhibit endotoxin-induced hyperglycemia by facilitating glucose utilization and not by stimulating glycogenesis or by antagonizing glycogenolysis in the liver or skeletal muscle.

Protamine sulfate is used clinically to reverse the anti-coagulant effects of heparin and in certain cases high protein, non-cardiogenic pulmonary edema develops. In the present study an initial stage of edema formation, namely, interstitial fluid accumulation around partially muscular extra-alveolar microvessels was observed in rats in situ after right ventricular injections of protamine. In addition, the endothelium of these microvessels displayed marked increases in plasmalemmal vesicles; however, disruption of the endothelium was not observed. Further, endothelial vesicle densities were unchanged and perivascular cuffs were not observed in either the nonmuscular extra-alveolar microvessels or the alveolar capillaries. Left ventricular injections of protamine failed to elicit the ultrastructural responses to protamine. Predosing the pulmonary microcirculation with heparin also served to prevent protamine-induced changes in the partially muscular microvessels. If it is assumed that heparin lowers the threshold for protamine-mediated responses in patients who develop edema, inhibition of protamine-induced changes by heparin predosing cannot be explained by the present data. Although evidence of increased endothelial vesiculation in the partially muscular microvessels was obtained, relative contributions of vesicles or of the junctional clefts to efflux from the pulmonary microvessels is not known. Thus, the mechanisms associated with a reduction of endothelial selectivity to macromolecular efflux after protamine administration remain to be defined.

Macroscopic collateral vessels are widely regarded as the primary source of blood flow to collateral-dependent myocardium. Microscopic coronary collateral vessels have also been described, but their functional significance is controversial. Experiments were conducted in 18 anesthetized dogs with chronic coronary artery occlusions. Indices of collateral function demonstrated that all hearts were well-collateralized. The previously occluded coronary artery was cannulated distal to the obstruction for measuring retrograde flow before and after injection of either 13 microns or 84 microns emboli. Mean arterial pressure and heart rate were not altered by coronary embolization. Embolization with 13 micron spheres caused retrograde flow to increase by 43% (n = 11), whereas embolization with 84 micron spheres had no effect on retrograde flow (n = 7). Retrograde flow dislodged occlusive 84 micron spheres, since these spheres were found in the retrograde flow, and since antegrade flow increased by 250% after retrograde flow diversion. These findings demonstrate that collateral vessels less than 84 micron diameter contribute significantly to perfusion of chronically collateral-dependent myocardium.

In the development of disease of the glomerular capillary bed there is a triple association between loss of nephrons, adaptive hyperfunction of residual glomeruli, and hypertrophy and sclerosis of these glomeruli. Sclerosis is closely associated with hypertrophy, and both are closely tied to loss of nephrons. This paper quantifies the response over a period of 12 weeks of superficial cortical (SC), midcortical (MC) and juxtamedullary (JM) glomeruli of the Munich Wistar rat to the ablation of approximately 5/6 of renal tissue. The mean areas of peripheral and mesangial glomerular basement membrane (GBM) were estimated by stereologic methods. While the overall estimated area of the GBM increased in response to ablation by a factor of 2.4, the peripheral GBM area increased only by a factor of 2.15, and by way of contrast, the mesangial GBM area by a factor of 3.25. The latter difference is interpreted as a measure of glomerulosclerosis. There are no marked differences between the changes in SC, MC, or JM glomeruli. These findings are consistent with the association of glomerular hypertrophy and glomerulosclerosis, and with recent suggestions that glomerular hypertrophy and sclerosis following subtotal renal ablation are driven by local or circulating growth factors.

Xanthines have been employed clinically to treat asthma and related pulmonary conditions because of their bronchodilator properties. In addition, xanthines have been reported to block and/or attenuate the increase in microvascular permeability to macromolecules produced by some putative inflammatory mediators. In order to more completely assess the anti-inflammatory capabilities of xanthines, we have infused aminophylline intra-arterially in the canine forelimb prior to and during a local intra-arterial infusion of histamine. Forelimb prenodal lymph flow, protein concentration and protein transport were used as indices of transvascular fluid and protein flux. Infusion of histamine (4 micrograms/min) significantly decreased forelimb arterial pressures and increased lymph flow, protein concentration and protein transport. Aminophylline infusion (10 mg/min) decreased forelimb arterial pressures but did not affect lymph parameters. Histamine infusion during infusion of aminophylline increased lymph parameters but the increases were markedly less than with histamine infusion alone. Infusion of aminophylline (20 mg/min) decreased forelimb arterial pressures and systemic pressure. Subsequent histamine infusion resulted in small but significant increases in lymph parameters. These data indicate that aminophylline infusion can blunt the ability of subsequently administered histamine to increase microvascular permeability as evidenced by the attenuation of the increases in lymph flow, protein concentration and protein transport.

The relationship between striated muscle tissue oxygenation during hyper- and hypocapnia, and lactate levels and venous pO2 (pvO2) was studied in a rabbit model. Seven rabbits were ventilated with constant volume during ether anesthesia, and arterial pCO2 (paCO2) was varied by addition of CO2. Muscle tissue oxygenation was measured with a multichannel electrode on the striated muscle surface, the results presented as oxygen pressure distributions (OPD:s). The principal result during hypercapnia (paCO2 9.9 kPa) was a tendency toward increased mean oxygen pressure (ptxO2) of the OPD; OPD shape was normal in 5/7 runs. Arterial lactates (aLa) decreased. During duplicate hypocapnia to paCO2 2.9 and 2.8 kPa ptxO2 decreased, but only in 4/14 runs were tissue oxygen pressures (ptO2) below 0.6 kPa found. OPD shape was scattered in 6/14 runs indicating disturbance in regulation of tissue oxygenation (but without signs of hypoxia). An increase in aLa was found, as well as a decrease in arterio-venous lactate difference (avDLa). Lacking direct blood flow measurements, these two results could not be interpreted as increased lactate efflux per se. Muscle lactates (mLa) were high but, on average, not higher than a control group. A decrease in pvO2 was seen during hypocapnia. Subgrouping OPD:s according to shape and presence of low ptO2 values did, however, suggest that lactate was released in cases with low ptO2 values: a covariation was seen in runs with low oxygen pressures between high arterial and muscle lactates, decreased avDLa and pvO2; runs with scattered OPD:s had only intermediately high lactates and low avDLa and pvO2 when compared to normally shaped OPD:s. In this study, hypercapnia influenced striated muscle tissue oxygenation only to a minor degree while hypocapnia influenced it more but not as much as expected. Only when low oxygen pressures were present in the OPD:s were there indications of peripheral lactate release.