calcimycin and Vascular-Diseases

Platelets-isolated or in conjunction with leukocytes-interact with vessel walls in many experimental and human diseases. Several mediators are held responsible for platelet activation and interaction with leukocytes, among which PAF-acether (platelet-activating factor) is a prime candidate. This phospholipid mediator is released by most inflammatory cells, including neutrophils, by isolated organs such as kidney and heart, is a potent platelet and neutrophil agonist, and exerts major vasoactive properties. Its biosynthesis involves a two-step enzymatic process yielding the active molecule from the membrane alkyl-ether choline-containing phospholipids. The first step implicates a phospholipase A2 that hydrolyzes a long-chain fatty acid (which can be arachidonic acid) from membrane phospholipids, leaving the intermediate compound lyso PAF-acether, a PAF-acether precursor that is acetylated by an acetyltransferase in a second step. It can also result from deacetylation of PAF-acether by an acetylhydrolase. PAF-acether release might explain the intervention of platelets in diseases such as glomerulonephritis and allergic vasculitis, in which the involvement of neutrophils and platelets is frequently noted. The end result of these complex sets of cell-to-cell interactions is the release of most known inflammatory mediators, influencing vascular permeability, cell infiltration, and smooth muscle contraction. Nevertheless, direct evidence for the implication of these rather well-defined cellular and molecular interactions in human pathologic states remains to be obtained.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Calcimycin; Humans; Hypersensitivity; Kidney Diseases; Platelet Activating Factor; Rabbits; Vascular Diseases

We sought to determine the effects of secondhand smoke (SHS) exposure on vascular reactivity in newborn and infant rats.. Secondhand smoke exposure increases cardiovascular risk. Secondhand smoke-induced endothelial dysfunction has been demonstrated in older teenagers and young adults. We have previously shown in adult rabbits that SHS induces atherogenesis and endothelial dysfunction. The effects of SHS on vascular function in the offspring of SHS-exposed mothers and in infants are unknown.. In this study the effects of in-utero (21 days) and neonatal (28 days) exposure to SHS were examined in 80 rats, 4 weeks of age, in a 2-by-2 design study. Rats were exposed to sidestream smoke in smoking chambers. Aortic rings were excised and isometric force responses to phenylephrine, acetylcholine, A23187 and nitroglycerin were studied in organ baths.. Neonatal SHS exposure reduced animal weight (p=0.009). In-utero exposure increased the sensitivity (decreased the EC50) of aortic rings to phenylephrine (p < 0.0005), as did neonatal exposure (p=0.01). Maximal contraction to phenylephrine was reduced by in-utero exposure (p=0.04). In-utero SHS exposure reduced maximal endothelium-dependent relaxation to acetylcholine (p=0.04) and increased the EC50 (p=0.05), suggesting impaired sensitivity to acetylcholine. In-utero exposure decreased the sensitivity (increased the EC50) to the endothelium-independent vasodilator nitroglycerin (p=0.003).. Secondhand smoke has detrimental effects on vascular smooth muscle function in the newborn.

Topics: Acetylcholine; Animals; Animals, Newborn; Aorta, Thoracic; Calcimycin; Cotinine; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Ionophores; Maternal Exposure; Muscle, Smooth, Vascular; Nicotine; Nitroglycerin; Phenylephrine; Pregnancy; Rats; Tobacco Smoke Pollution; Vascular Diseases; Vasoconstriction; Vasoconstrictor Agents; Vasodilator Agents

There has been a prejudice that diabetes modulates the function of saphenous vein in a manner that predisposes to bypass graft failure, although most of the evidence accrues from animal studies. We have investigated the effect of diabetes on the vasodilator responses and ultrastructure of saphenous vein harvested from patients undergoing infrainguinal bypass surgery for limb salvage and the development of stenoses within the vein grafts. Of 55 consecutive patients undergoing vein bypass surgery for critical ischemia, 16 (29%) were diabetic: diabetes was not a risk factor for graft stenosis, which occurred in 17 of 56 (30%) grafts. Endothelium-dependent relaxation by nitric oxide pathways stimulated after receptor activation (bradykinin and thrombin) was not different in vein rings from diabetic (n = 12) and nondiabetic patients (n = 12). Prostarioid-mediated vasorelaxation was absent in vein rings from diabetic patients, and the production of 6-keto prostaglandin F(1alpha) (PGF(1alpha)) from diabetic vein was only 66 +/- 27 pg x cm-2 x min-1 compared with 112 +/- 20 pg x cm-2 x min-1 from control vein (P = 0.011). Fibrinogen-mediated vasorelaxation, normally inhibited by K+ channel blockers, was negligible in vein from diabetic patients. No ultrastructural differences were observed between the endothelium of saphenous vein harvested from diabetic and nondiabetic patients. However, diabetes was associated significantly with the presence of spiraled collagen in media. The maintenance of receptor-activated stimulation of nitric oxide pathways and the damping of the response to fibrinogen in saphenous vein endothelium may provide, in part, for the good prognosis of vein graft surgery in diabetic patients: diabetes is not a risk factor for early (12 months) infrainguinal vein graft stenosis.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Blood Vessel Prosthesis; Bradykinin; Calcimycin; Collagen; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium, Vascular; Female; Fibrinogen; Humans; In Vitro Techniques; Indomethacin; Ischemia; Leg; Male; Microscopy, Electron; Middle Aged; NG-Nitroarginine Methyl Ester; Postoperative Complications; Saphenous Vein; Time Factors; Vascular Diseases; Vascular Surgical Procedures; Vasodilation

Topics: Adenosine Diphosphate; Animals; Aspirin; Blood Platelets; Calcimycin; Collagen; Eicosanoic Acids; Epinephrine; Epoprostenol; Fatty Acids, Unsaturated; Humans; Platelet Aggregation; Rats; Vascular Diseases