Microcirculation, endothelium, and lymphatics最新文献

To estimate functional diffusion distances, the distribution of perfused capillaries was calculated in dog myocardium. A fluorescent dye was injected via a femoral vein in 6 anesthetized, open-chest dogs, and passed once through the coronary circulation (23 +/- 3 s). In 6 animals the dye circulated 4-20 min. In 6 animals the dye circulated for one pass following 2-3 min of asphyxia. The heart was then removed and frozen. Frozen sections from the left ventricule were cut, illuminated to excite the dye to fluoresce, and photographed. They were then stained by silver methenamine to mark all capillaries. The density of all capillaries was compared to that of capillaries containing fluorescent label. The distributions of capillaries were estimated by morphometry. In one pass of the normoxic coronary circulation, 66(+/- 4 SE)% of subepicardial and 60(+/- 4)% of subendocardial capillaries were detectably labeled. Their distribution approached a random pattern, and maximal distances to the nearest labeled capillary were lengthened by 50% compared to all capillaries. With multiple passes of the dye, or with asphyxia 76-79% of the capillaries were detectably labeled and their distribution approached the ordered pattern of the total capillary bed. We speculated that the unlabeled capillaries represented a spatially heterogeneous blood flow reserve.

The possible importance of facilitation of sodium-calcium (Na(+)-Ca2+) exchange by removal of extracellular magnesium ions ([Mg2+]o) in expression of endothelium-dependent relaxation was investigated in aortic rings isolated from female rats. Simultaneous [Mg2+]o withdrawal (0 mM Mg2+) and reduction in extracellular Na+ (Total [Na+]o = 84 mM), by replacement of NaCl with isosmolar amounts of sucrose in normal Krebs-Ringer bicarbonate (NKRB), induced significant increases of basal tone of denuded rat aortic rings, but not in tissues with intact endothelium. These vascular effects were not affected by indomethacin, phentolamine or atropine in any of the tissues tested. Reintroduction of 1.2 mM Mg2+ or removal of extracellular Ca2+ ([Ca2+]o) from the Mg2+ and Na(+)-deficient incubation media induced complete relaxation of the denuded tissues. Methylene blue (10(-5) M), an inhibitor of endothelium-derived relaxant factor (EDRF), potentiated tension development in intact tissues. These results suggest that: (1) as in vascular muscle, Mg2+ plays an important role in Ca2+ homeostasis in endothelial cells (EC), probably via Na(+)-Ca2+ exchange; and (2) such Mg(+)-regulated internal Na(+)-dependent Ca2+ entry participates in the expression of endothelium-dependent relaxation.

Calcitonin gene-related peptide (CGRP) is a 37 amino acid peptide which is found in high concentrations in the perivascular nerves innervating the resistance vessels of the peripheral circulation. In the current study we have infused CGRP at three infusion rates (.01, .1 and 1.0 micrograms/min into the brachial artery for thirty minutes at each infusion rate) in the isolated, innervated canine forelimb perfused at natural flow. We measured large artery and vein pressures, small artery and vein pressures and blood flows in both the skin and skeletal muscle circulations for the calculation of total and segmental (large artery, small vessel and large vein) vascular resistances. Infusion of the lowest dosage of CGRP produced slight vasodilation in some animals but did not significantly alter the mean resistances of all the animals as a group. The middle dosage resulted in a 55% decrease in total forelimb resistance and a small but significant decrease in systemic arterial pressure. The highest dosage of CGRP resulted in a 65% decrease in total forelimb resistance and a 34% decrease in systemic arterial pressure. The decreases in forelimb resistances were equally distributed between skin and muscle and were manifested in both large artery and small vessel resistances. The potent vasodilatory effects of CGRP and its concentration in perivascular nerves innervating the resistance vessels of the peripheral circulation suggests a potential role for CGRP in control of circulatory function under normal and/or pathophysiological conditions.

The effect of O-(beta-hydroxy-ethyl)-rutosides (HR), injected subcutaneously, was investigated on experimental acute lymphoedema in rat thighs. The oedema was reduced from a 30% increase over the normal weight, to one of 13%. When the macrophages were destroyed by the intraperitoneal injection of silica (for eight days before the initiation of lymphoedema) the oedema of the thigh increased to 41% - thus showing the importance of these cells in limiting high-protein oedemas. When HR was given to animals treated with silica the oedema was no longer reduced (42%). Thus HR reduces a high-protein oedema substantially via the macrophages.

Using the critical electrolyte concentration technique, with ruthenium red as a strain for polyanionic macromolecules, we examined the basement membranes of the rat choroid plexus. Concentrations of Na+ exceeding 3.0 M were required to reversibly inhibit discrete staining of endothelial and epithelial basement membranes by ruthenium red, whereas 2.5 M Na+ inhibited staining of renal pertitubular capillary basement membranes. The findings are consistent with recent evidence that basement membranes underlying fenestrated capillaries are more polyanionic that those underlying continuous capillaries, and suggest that basement membranes of the choroid plexus are more polyanionic than those of peritubular capillaries.

We have previously reported that perfused lymphatic vessels in the canine forelimb constrict in response to increased sympathetic nerve activity or local infusions of endogenous vasoconstrictor substances. In the present study we have assessed the effects of three endogenous vasodilators; acetylcholine, bradykinin and histamine on lymphatic vessel contractility. Each one of these agents, when infused intralymphatically, produced lymphatic constriction as evidenced by significant increases in lymphatic perfusion pressure. The threshold concentrations which produced lymphatic constriction were between 10(-6) and 10(-5) molar for acetylcholine and bradykinin and between 10(-5) and 10(-4) molar for histamine. Surgical exclusion of the lymph nodes and efferent lymph vessels from the perfused tissue did not significantly affect the observed response, indicating that the response occurs predominately in the prenodal segments of the lymphatic system. Infusion of acetylcholine and bradykinin into the arterial supply to the forelimb did not significantly alter lymphatic perfusion pressure, unlike the response seen when catecholamines are infused intra-arterially. Histamine displayed an unusual property in that it constricts lymph vessels upon initial administration but was thereafter completely ineffective. Constriction of lymphatic vessels by substances which are potent vasodilators clearly indicates that significant functional differences exist in endothelial cell/smooth muscle relationships between blood vessels and lymph vessels.

Platelet activating factor (PAF), a potent vasoactive lipid, may play an important role in the inflammatory process. In this study, we infused PAF intra-arterially to characterize its edematogenic potency in the canine forelimb. We have also assessed the ability of the beta 2-receptor agonist l-terbutaline to block PAF-mediated edema formation. The infusion of PAF at .25 micrograms/min, .5 micrograms/min and 1 micrograms/min increased forelimb arterial pressures and, at the two higher dosages, significantly decreased systemic arterial pressure. PAF infusions increased transvascular fluid and macromolecular flux as indicated by significant increases in skin lymph flow, protein concentration and protein transport. The intra-arterial infusion of l-terbutaline at 1 micrograms/min significantly decreased forelimb arterial pressures but did not affect small vein pressure, systemic pressure or forelimb lymph parameters. The subsequent infusion of PAF at .5 micrograms/min, during the continued infusion of l-terbutaline, failed to significantly affect forelimb lymph parameters. These data indicate that PAF is significantly more potent as an edematogenic agent in the forelimb than histamine or bradykinin. Furthermore, the blockade of PAF-mediated edema formation by l-terbutaline suggests that beta 2-receptor agonists may be capable of antagonizing the inflammatory actions of a wide variety of putative inflammatory mediators.

Endothelin is a potent vasoactive polypeptide isolated from cultured endothelial cells. However, there are relatively few studies of the action of endothelin on microvessels in vivo. To determine the effects of this compound on arterioles of normotensive and hypertensive rats, endothelin (1 x 10(-12) M to 1 x 10(-8) M) was dissolved in physiological salt solution and superfused over the cremaster muscle of 12-15 week old spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WKY) controls. Endothelin caused about a 55% constriction of second order arterioles and complete closure of most third order arterioles and all fourth order arterioles studied. SHR arterioles tended to be more sensitive to endothelin than those of WKY, although this difference was significant for only the third order arterioles. Endothelin induced contractions were significantly inhibited by 10(-6) M nifedipine in both WKY and SHR. These studies demonstrate that endothelin is a potent constrictor of skeletal muscle arterioles, and suggest that activator Ca2+ for endothelin induced contractions of these vessels enters the vascular smooth muscle cells through dihydropyridine sensitive calcium channels.

The lungs provide not only respiratory function, but also are involved in metabolism and maintaining homeostasis. The lungs receive the entire cardiac output, circulating blood cells and hormones. The metabolically active vascular endothelial cell lining participates in degrading and synthesizing various hormones and vasoactive substances which affect the pulmonary as well as systemic circulation. The normal state is maintained through complex interaction of the circulating hormones, maturation of the system, the physiological state of the lung cells and metabolism. Any noxious stimulus can disrupt this delicate balance and adversely affect the metabolism of various substances, thus producing an abnormal state. In this review, some of these factors including therapeutic implications are discussed.

We have previously demonstrated that magnesium therapy attenuates monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy in rats. In this report we evaluate the effect of oral magnesium therapy on the pulmonary vasculature of monocrotaline-treated rats. Lung sections were prepared for light microscopic examination, and the medial wall thickness of pulmonary arteries of less than 100 microns in diameter was measured. The mean medial wall thickness of control rats was 6.98 +/- 1.16% of the external diameter of the pulmonary artery, the monocrotaline group had a significant increase in medial wall thickness (14.61 +/- 1.52%, p less than 0.005 vs control); in contrast 75% of MCT + magnesium group revealed a significant reduction in medial wall thickness (8.13 +/- 1.26%, p less than 0.02, vs monocrotaline group). Magnesium therapy alone had no effects on pulmonary vasculature. We conclude that magnesium has significant beneficial effects on monocrotaline-induced pulmonary hypertension and the accompanying vascular lesions.