摘要:

Mechanotransduction by vascular smooth muscle (VSM) is defined as a cellular response (contraction, secretion, growth, division) to transmural pressure or stretch. This review includes an overview of the physical forces VSM cells experience in vivo, consideration of experimental techiques used to study VSM mechanotransduction, and a discussion of the scientific literature pertinent to the individual cellular components that have been implicated in the transduction of physical forces. These include: the extracellular matrix, integrins, ion channels, the sarcoplasmic reticulum, second messenger systems, contractile proteins, and the cytoskeleton.

ISSN:1018-1172    

DOI:10.1159/000159102

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Vascular smooth muscle glycogen stores are traditionally thought to be small compared to other glycogen-containing tissues such as striated muscle or liver. However, glycogen has been thought to be an important carbon substrate for oxidative metabolism in support of contraction in vascular smooth muscle. We examined the synthesis and degradation of glycogen in isometrically mounted hog carotid artery using 13C-NMR spectroscopy. The rate of net glycogen synthesis from 1-13C-glucose was found to be constant during the first 8 h of incubation of carotid arteries with 10 mM glucose at 37 °C and then decreased towards a rate of zero by 14 h of incubation. During 8 h of incubation in the presence of 5 mM glucose, the content of glycogen increased from 1.5 to 8.1 µmol/g blot weight in the absence of insulin and to 11.4 µmol/g blot weight in the presence of 0.5 U/ml insulin. During prolonged glycogen loading, there was a simultaneous degradation of previously synthesized 6-13C-glycogen during synthesis of 1-13C-glycogen from 1-13C-glucose indicating substrate cycling of glycogen metabolism. This substrate cycling results in a pattern of glycogen utilization in which the most recently synthesized glucosyl units of glycogen are utilized only slightly more readily than the previously synthesized glucosyl units of glycogen. We conclude that glycogen stores are larger and more dynamic than previously thought in vascular smooth muscle consistent with an important role for glycogen as a carbon source for smooth muscle energy metaboli

ISSN:1018-1172    

DOI:10.1159/000159103

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Measurements on the directional organization of collagen are necessary for relating the structure and mechanical function of blood vessels. The birefringent optical property of collagen has enabled us to assess the collagen architecture for brain arteries, which are prone to spasm and aneurysm formation. Using the universal stage and polarizing microscope, we measured the three-dimensional organization of the collagen of the main layers of the artery wall, and examined the effect of distending pressure on that organization. Adult arteries obtained from autopsy were fixed at one of three distending pressures, 30, 120 and 200 mm Hg; they were embedded in paraffin and sectioned parallel to the vessel axis at 4 µm thickness. Sections were stained with picrosirius red, a birefringent enhancement stain specific for collagen. Orientation data were obtained from tangential sections from thirteen arteries. We chose to use tangential sections that graze the curving surface of individual layers, to permit measurements that are equally sensitive to fibres in the mechanically meaningful range of directions including longitudinal, helical and circumferential. Each measurement was from a single fibre or group of fibres at a specific location; the mean direction and its variation of alignment within each artery layer were calculated. In some arteries, the adventitia and subendothelium measurements were separated into sublayers, distinguishable by the birefringent optical appearance. Main findings included a substantial component of longitudinal fibres in the adventitia and subendothelium, highly varied in coherence and mean direction, and a thin collagen layer of the adventitia, radially outside the medial muscle cells, that was highly organized circumferentially (circular standard deviation of 9°). At higher pressures, the collagen fabric of all the layers was increasingly coherent and more circumferential in directio

ISSN:1018-1172    

DOI:10.1159/000159104

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Rabbit thoracic aorta was used to determine the effects of decreasing PO2 on the mechanical properties of contractions in response to norepinephrine (NE) and KC1. Aortae were aerated with 45% O2/5% CO2/50% N2 and stimulated with 10 µM NE or 50 mM KCl. At 5 min of stimulation, 5% CO2/95% N2 aeration was introduced for 15 min, defined as hypoxia. This time period was previously shown to produce similar decrease in [ATP] in either stimulation condition. Force, stiffness and isotonic shortening velocity were monitored during the initial stimulation, during hypoxia and during re-oxygenation. Hypoxia produced a substantial and rapid decrease in force and a concomitant decrease in stiffness during NE stimulation; delayed and smaller decreases in force and stiffness were observed during KC1 stimulation. The force-stiffness relationship was steeper during KC1 than NE stimulation, and hypoxia did not affect these relationships. Isotonic shortening velocity was significantly depressed by hypoxia during both stimulations although the decrease during KC1 stimulation required a longer time. These data demonstrate that relaxation of an agonist-induced contraction in response to hypoxia results from a decrease in the number of activated crossbridges and not formation of rigor bridges

ISSN:1018-1172    

DOI:10.1159/000159105

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Mesenteric endothelial cell function and immunoreactivity for substance P and nitric oxide synthase (NOS) were examined in control rats and rats treated with capsaicin as neonates to destroy primary afferent nerves. Endothelial vasodilator function was examined pharmacologically in the methoxamine raised-tone isolated perfused mesenteric arterial bed. Endothelial immunoreactivity for substance P and NOS was examined at the ultrastructural level by electron-microscopic immunocytochemistry. The endothelium-dependent vasodilators acetylcholine and adenosine 5’-triphosphate elicited dose-dependent relaxations which were not different between control and capsaicin-treated rats. Dose-dependent relaxations to endothelium-independent vasodilators, calcitonin gene-related peptide and sodium nitroprusside, were also unchanged by capsaicin treatment. Positive staining for substance P was detected in 25% of endothelial cells in both control and capsaicin-treated rats. Positive staining for NOS was detected in 50% of endothelial cells in control rats, and this was not changed by capsaicin treatment. These results confirm that endothelial substance P is independent of substance P contained in sensory nerves. Long-term sensory denervation does not produce changes in endothelium-dependent or -independent relaxation, or in the number of endothelial cells showing positive labelling for substance P and NOS in rat mesenteric arterie

ISSN:1018-1172    

DOI:10.1159/000159106

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The mitogenic activities of low (LDL)- and high (HDL)-density lipoproteins have been examined in cultures of human vascular smooth muscle cells (VSMC). LDL and HDL3 dose-dependently (EC50 values ∼50 µg/ml) stimulated DNA and protein synthesis ([3H]-thymidine and [3H]-leucine incorporation, respectively) in the absence of exogenously added mitogens. The synthetic responses of VSMC to combinations of LDL and HDL3 were additive, indicating that each lipoprotein mediates discrete effects. LDL or HDL3 promoted VSMC proliferation under strict mitogen-free conditions, but this growth response was not sustained. VSMC exposed to combinations of lipoproteins (either LDL or HDL3) and growth factors (either PDGF-BB, EGF, bFGF or IGF) exhibited synergistic DNA synthesis responses. In the combined presence of PDGF-BB and either LDL or HDL3, VSMC proliferation was sustained. Anionized lipoprotein preparations (oxidized, acetylated, carbamylated or malonimylated) also stimulated DNA and protein synthesis. Since the antioxidant β-ydroxylated toluene did not block the effect of native LDL on DNA synthesis, and fucoidin, a specific competitor for the ‘scavenger’ receptor, did not inhibit oxidized LDL-induced DNA synthesis, activation of mitogenic signals by lipoproteins does not depend on lipid peroxidation. Rather, the apparent intrinsic mitogenic potential of lipoproteins may depend upon their direct activation of replication-coupled signal transduction

ISSN:1018-1172    

DOI:10.1159/000159107

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The possible endothelial factors involved in endothelium-dependent relaxations induced by acetylcholine (ACh) in aorta, mesenteric and femoral arteries of rabbit were analyzed. In thoracic aorta precontracted with noradrenaline, NG-nitro-L-arginine methyl ester (L·NAME) and methylene blue (MB), inhibitors of nitric oxide (NO) synthase and guanylate cyclase, practically abolished ACh relaxation. This relaxation was reduced by the Na+ pump inhibition with ouabain and K+-free solution, and by the blockade of Ca2+-dependent K+ channels with tetraethylammonium (TEA). Ouabain reduced the relaxation produced by the NO donor, sodium nitroprusside (SNP). In the mesenteric artery, L·NAME and MB produced a small reduction of ACh relaxation. However, ouabain, K+-free medium and TEA markedly decreased this relaxation. SNP induced a relaxation which was diminished by ouabain. In segments precontracted with high K+, ACh relaxation was abolished by L·NAME and MB. In femoral arteries, L·NAME and MB reduced ACh relaxation. The stimulated cGMP concentrations caused by ACh or SNP were less in the aorta than in mesenteric and femoral arteries. These results suggest that ACh relaxation is mediated: in aorta by endothelial NO which may hyperpolarize to some extent the smooth muscle cells through the sodium pump activation, in mesenteric artery by endothelium-derived hyperpolarizing factor and NO, the latter being clearly expressed in segments contracted with high K+, and in femoral artery essentially by endothelial NO rele

ISSN:1018-1172    

DOI:10.1159/000159108

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We investigated the effects of angiotensin converting enzyme inhibitors on acetylcholine-induced endothelium-dependent vasodilation in the presence of nitroglycerin tolerance in rings of rabbit thoracic aorta mounted in tissue baths and precontracted with 10–6M norepinephrine. The vasorelaxant effects of acetylcholine were measured before and after 1 h treatment with 5 × 10–4M nitroglycerin. The acetylcholine dose-response curve shifted to the right after the induction of nitroglycerin tolerance. Pretreatment with captopril (a sulfhydryl angiotensin converting enzyme inhibitor), but not with M-1 (a metabolite of delapril and a nonsulfhydryl angiotensin converting enzyme inhibitor) restored acetylcholine-induced relaxation. Pretreatment with N-acetylcysteine also restored reduced acetylcholine-induced relaxation. These results suggest that the sulfhydryl group plays a major role in restoration of reduced acetylcholine-induced vasodilation in the presence of nitroglycerin toler

ISSN:1018-1172    

DOI:10.1159/000159109

出版商:S. Karger AG    

年代:1995

数据来源: Karger