Blood vessels最新文献

The aim of this work was to evaluate the effect of buflomedil on hemorheologic, hemodynamic and microcirculatory properties in diabetic patients. Patients were 20 noninsulin-dependent diabetics with distal arteriopathy characterized by chronic hypoxia (transcutaneous oxygen pressure = 25.2 +/- 4.8 mm Hg). They were randomly assigned to two groups for a double-blind study versus placebo. The treatment consisted of a 4-hour intravenous perfusion of 400 mg of buflomedil or placebo as a daily dose during 7 days. Results showed significant improvements in hemodynamic parameters such as post-occlusive peak flow and time to peak flow at the end of buflomedil treatment. In the same manner, the transcutaneous oxygen pressure was found to be significantly increased after buflomedil treatment, whereas there was no modification by placebo. Indeed, red cell aggregation was significantly less important as a result of buflomedil treatment whilst red cell deformability was found to be significantly increased. These hemorheological improvements make the blood flow redistribution through the microcirculatory network easier and lead ultimately to better tissue oxygenation.

Autologous blood placed around the basilar artery caused angiographic narrowing with a biphasic time course. The first immediate phase was reversed by intraarterial papaverine; the second exhibited an increasing component of narrowing which was papaverine-resistant. In vitro studies showed that vessels became increasingly stiffer, less capable to develop active tone, and less responsive to vasoconstrictors and vasodilators. The papaverine-resistant component of angiographic narrowing (in vivo) could be directly correlated with loss of contractility and increased artery wall stiffness (in vitro).

In vitro studies on the action of buflomedil (BFL) and its derivative CRL 41034 on the polymorphonuclear cells (PMN) has been performed using functional tests and scanning electron microscopy. The two drugs exhibited the same effects. BFL does not change the in vitro chemotaxis of PMN, but exhibits a regulatory effect on ZMS-induced aggregation of these cells. BFL also appeared to decrease superoxide production of PMN, in a dose- and time-dependent way. The cytoskeleton F-actin polymerization, analyzed through the binding of rhodamin-phalloidin, was increased when the total F-actin of the cells was unchanged. When cell extensions were studied morphologically a change in the shape of the pseudopods as well as the general aspect of the PMN (cottonous aspect) was observed as compared to controls. These drug-induced modifications in the shape change may be efficient in adhesion processes. Finally this latter effect and the influence on oxygen metabolite production could be another means of BFL to protect the microvessels during ischemia, in addition to its vasomotion promoting properties.

Morphometric studies conducted on the blood vessels of the spontaneously hypertensive rat have provided evidence that medial hypertrophy is a key characteristic of the vascular change which occurs in hypertension. In the present study, we determined whether 3-methylhistidine (3MH), a post-translationally modified amino acid which is found uniquely in the actin and myosin of muscle, could provide a biochemical marker of such change. Our results indicated that the concentrations of 3MH were selectively elevated in the blood vessels from the spontaneously hypertensive rat, when compared with concentrations in vascular tissues from the Wistar-Kyoto rat. The concentrations of 3MH in non-vascular tissues were similar in the two strains. Chronic captopril treatment prevented the development of hypertension in the spontaneously hypertensive rat and was associated with a reduction of the vascular concentrations of 3MH. We therefore conclude that blood vessel concentrations of 3MH are a useful biochemical index of the changes in vascular smooth muscle contractile protein which occur during the development of hypertension in the spontaneously hypertensive rat.

Two commonly used methods for examining the physiological and pharmacological properties of isolated resistance arteries are the ring-mounted preparation and the cannulated, pressurized vessel. Each technique is discussed and consideration given to limitations and advantages. Also presented are examples of comparative differences between them, and practical experimental schemes for calibrating cannulae and for perfusing resistance arteries. Although both methods are valuable, the cannulated approach may better reflect the in vivo properties of the arteries.

Cyclic GMP (cGMP) mediates the relaxing action of a variety of vasodilator drugs and endogenous vasodilator substances. Cyclic AMP (cAMP) mediates relaxation by beta-adrenergic agonists as well as other activators of adenylate cyclase. Both second messengers appear to reduce the concentration of intracellular Ca2+ in vascular smooth muscle cells, thus affecting relaxation. The presence of cGMP-dependent protein kinase in vascular smooth muscle cells is required for the reduction of Ca2+ by cAMP and cGMP, suggesting that this enzyme mediates the relaxing effects of both cyclic nucleotides. Although the specific substrate proteins for cGMP-dependent protein kinase are not well characterized in vascular smooth muscle, new evidence indicates that Ca2(+)-ATPase activation by phosphorylation of phospholamban by the kinase may underlie the mechanism of action of cyclic-nucleotide-dependent relaxation.

Considerable evidence has been accumulated for a renin-angiotensin system in the blood vessel wall with local generation of both angiotensin I and angiotensin II that plays an important role in blood pressure regulation. A major source for vascular renin is renal renin taken up by the arterial wall from the circulation. However, recent studies suggest that, in addition, local synthesis of components of the renin-angiotensin cascade also takes place in the vessel wall. The contribution that these locally derived components make to the functions of the vascular renin-angiotensin system remains to be elucidated. Studies, particularly in vitro, suggest that vascular pathways for angiotensin generation not involving renin or angiotensin-converting enzyme may also exist. As in the case of the locally derived components of the renin-angiotensin cascade, the role of these alternate pathways in the physiology of the vascular wall remain to be defined.

Atrial natriuretic peptide (ANP) exhibits a wide spectrum of cardiovascular, endocrine, metabolic and renal actions. cGMP is the major mediator of ANP at the cellular level and only tissues possessing particulate guanylate cyclase appear to present ANP-induced actions. Three types of ANP receptors have recently been cloned. Two of them (A and B receptors) are homologous and contain guanylate cyclase catalytic domains. The C receptor could possibly regulate the metabolic fate of ANP. Data obtained by the radiation inactivation method suggest the presence of an inter- or intramolecular inhibitory component of nearly 90 kilodaltons that represses the catalytic activity of guanylate cyclase within its membrane environment. The mechanism of guanylate cyclase stimulation by ANP could involve this inhibitory component. Preliminary data suggest that the hyperresponsiveness of the particulate guanylate cyclase/cGMP system in hypertension occurs through modulation of the inhibitory component.

Endothelial cell seeding procedures have been developed to line prosthetic bypass grafts used in peripheral vascular disease; however, because of current inefficient cell harvest techniques a high ratio of vein-to-graft area is necessary. This study was done to determine if the use of papaverine, a smooth muscle cell relaxant, would affect the number or viability of endothelial cells harvested from canine external jugular veins. Using a 0.12 mg/ml solution of papaverine in tissue culture medium to bathe the veins during dissection and excision, the viable cell yield was 2.20 +/- 1.16 (cells x 10(4)/cm2). A control group of veins using standard dissection technique gave a yield of 0.97 +/- 0.40 (p = 0.025). A second group of veins dissected while bathed in tissue culture medium alone gave a yield of 1.82 +/- 0.75, compared to a yield of 2.73 +/- 0.45 for papaverine harvested veins (p = 0.009). Percent cell viability was not significantly different for any of the groups: 73, 70, and 76% for papaverine, control and media only veins, respectively. The papaverine-harvested cells and those harvested with medium alone grew to 95% confluence in tissue culture in 9.8 +/- 1.1 and 9.9 +/- 0.9 days, respectively. Compared to conventional surgical techniques, use of papaverine more than doubled the endothelial cell yield from excised vein segments without adversely affecting viability or rate of growth in cell culture.