ISSN:1062-3329    

DOI:10.3109/10623329409024630

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

In addition to passive factors, pulmonary vascular tone is under the control of adrenergic, cholinergic, NANC vasodilator nerves and humoral mechanisms. Hypoxic pulmonary vasoconstriction plays an important role in the active control of pulmonary vascular tone. Adrenergic nerves, HPV and vasoconstrictor humoral substances are the vasoconstricting forces, whereas cholinergic, NANC mechanisms and vasodilator humoral substances are the dilating factors. Basal and stimulated release of NO from endothelial cells also represents dilating force. Thus, a balance between these two sets of opposing forces determines the normal resting pulmonary vascular tone. Disturbance of this balance may result in or/and contribute to the development of some pulmonary vascular diseases such as pulmonary hypertension. Endothelium-derived NO plays an important role in the regulation of pulmonary vascular tone. It inhibits adrenergic contraction, hypoxic pulmonary vasocon-striction and the contractile response to many vasoconstrictors. NO mediates the vasodilator responses to NANC stimulation and variety of pulmonary vasodilator substances. NO also play a part in the perinatal pulmonary vascular adaptation.

ISSN:1062-3329    

DOI:10.3109/10623329409024631

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Stress fiber expression and fibronectin distribution were studied in perfusion-fixed,en facepreparations of chick aorta and mesenteric artery stained with fluorescent phalloidin, anti-fibronectin or anti-vinculin. Transmission electron microscopy, ultrastructural immuno-cytochemistry and confocal laser scanning microscopy were also used. Thick stress fibers aligned parallel to the vessel axis were prevalent in the aorta and the proximal part of the mesenteric artery, but their number and caliber decreased with vessel size. Fibronectin fibrils were also aligned parallel to the direction of blood flow in the aorta and the proximal portion of the mesenteric artery, the degree of alignment gradually decreasing as the mesenteric artery diminished in size. Stress fibers and fibronectin fibrils were often colinear and appeared to be tightly coupled, forming a structure similar to the adhesion plaque of cultured cells. In a small area immediately downstream from a flow divider, endothelial cells were polygonal and both stress fiber expression and axial fibronectin organization were lost. Irregular fibronectin patterns were also seen in the distal part of the mesenteric artery, which contained aligned endothelial cells with only a few or no stress fibers. No correlation between cell shape and fibronectin patterns was noted. Endothelial cell stress fibers, whose expression is influenced by fluid flow, may have a role in the alignment of fibronectin in large arteries.

ISSN:1062-3329    

DOI:10.3109/10623329409024632

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Systemic hypoxia (inspired oxygen of 10%) constricts large arterioles (A1) and dilates small arterioles (A3) in striated muscle. The possible role of endothelium-derived relaxing factor (EDRF) or prostaglandins in mediating these responses was examined, as were the arteriolar response to systemic hypoxia in 1K1C (1-kidney, 1-clip) hypertensive rats and EDRF involvement in this response. In the cremaster muscles of anesthetized rats, hypoxia-induced A1 constriction was similar in normotensive and hypertensive animals and was not affected by the blockade of prostaglandin synthesis with mefenamic acid or by EDRF inhibition with hydroquinone (an EDRF inactivator) or L-Nω-nitro-arginine (L-NNA) (an EDRF synthesis inhibitor). A3 dilation in normotensive animals was unaffected by mefenamic acid, but was significantly (p<0.05) attenuated by hydroquinone and L-NNA. Arteriolar dilation during systemic hypoxia was significantly less (p<0.05) in the hypertensive compared with the normotensive groups and not altered by hydroquinone or L-NNA, but A3 dilation in response to nitroprusside was similar in the hypertensive and normotensive animals. The present data indicate that both EDRF-dependent and EDRF-independent mechanisms mediate the hypoxia-induced dilation of small arterioles in the striated muscle of normotensive rats. Small arterioles in the striated muscle of 1K1C hypertensive rats are less responsive to systemic hypoxia, primarily owing to depressed EDRF-dependent vascular mechanisms.

ISSN:1062-3329    

DOI:10.3109/10623329409024633

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Pretreatment of rat large vein endothelial cells (ECs)in vitrowith cytochalasin B (CB, 1×10−5M) significantly reduced the narrowing of these cells in response to subsequent exposure to platelet-activating factor (PAF, 2×10−6M) or the calcium ionophore A23187 (2×10−5M). PAF (5×10−6M) also caused leakage of colloidal carbon (CC) into the walls of microvessels of the rat small intestinal vasculature when included in a gelatin-containing artificial perfusatein vitro. Pretreatment of the vessels with CB (1×10−6M) or phalloidin (1×10−7M) reduced this CC labelling. The results obtained provide evidence for the involvement of actin filaments in the EC shape changes, or“contractions”, that are thought to occur in inflammatory conditions.

ISSN:1062-3329    

DOI:10.3109/10623329409024634

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

The contractile response of renal arterial muscle to porcine endothelin (ET-1) was studied by measuring vessel diameters and vascular smooth muscle transmembrane potentials in small arteries (300–600μm inside diameter) isolated from dog kidneys and cannulated with micropipettes connected to a pressurized reservoir system. Endothelin (10−12to 10−8M) was a potent constrictor of these vessels and caused a concentration-dependent contraction at a mean EC50(median effective concentration) of 3.1 (±1.15)×10−10M. Endothelin also produced a modest depolarization of arterial smooth muscle much smaller than had previously been demonstrated to occur in these vessels in response to norepinephrine or transmural pressure elevation. Endothelin-induced contractions were partially inhibited by 10−6M nifedipine and abolished by Ca2+-free solution. Although the influx of extracellular Ca2+ions through dihydropyridine-sensitive pathways contributes to endothelin-induced contractions of these vessels, electromechanical coupling does not appear to be the sole determinant of the magnitude of endothelin-induced constriction in canine small renal arteries.

ISSN:1062-3329    

DOI:10.3109/10623329409024635

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

A growth factor with an apparent target cell specificity for human umbilical vein endothelial cells (HUVEC) has been identified in serum-free medium conditioned by human retinal pigment epithelial (HRPE) cells. This factor, designated vascular endothelial growth factor-like mitogen (VEGF-like mitogen), was purified 4,200-fold by a three-step chromatography consisting of Mono Q ion-exchange chromatography, heparin-Sepharose affinity chromatography and hydrophobic chromatography on a C4reverse phase HPLC column. The VEGF-like mitogen has a molecular mass of 43,000 and is composed of two apparently identical subunits as assessed by silver-stained SDS/PAGE with or without prior reduction. The purified factor has a maximal mitogenic effect on HUVEC at a concentration of approximately 10 ng/ml. In contrast to bFGF, aFGF and PD-ECGF, the VEGF-like mitogen is a secreted dimeric glycoprotein. It is not mitogenic for human skin fibroblasts (HFIB), human RPE cells and human dermal keratinocytes (HDK). Our results show (that the VEGF-like mitogen shares biochemical, structural, antigenic and biological properties with the mitogens of the VEGFNPF family. Immunoblotting using an anti-VEGF antiserum identifies the purified mitogen as VEGF/VPF.

ISSN:1062-3329    

DOI:10.3109/10623329409024636

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Objectives Impaired tissue reperfusion may be an important limiting factor for long-term hypothermic cardiac preservation. Cardiac function and recovery of coronary responses to endothelium independent and dependent vasodilators were tested before and after one day of preservation by cold perfusion with a normal extracellular solution containing the contraction uncoupler 2,3, butanedione monoxime (BDM) with or without reperfusion with nitroprusside (NP) plus adenosine (Ade) or plus the nucleoside transport inhibitor, nitrobenzylthioinosine (NBTI).Methods Guinea pig hearts (n = 70) were isolated and perfused at constant pressure during normothermic conditions (37°C). Groups 1 and 2 were perfused for 8 hrs without cold perfusion (time control); group 2 was also infused with arginine vasopressin (AVP) for 6 hrs; groups 3–5 were infused with BDM before, during, and initially after 22 hrs of constant, low flow hypothermic (3.8°C) perfusion; group 3 was also infused with NP and Ade, and group 4 with NP and NBTI, for 10 min before rewarming, during rewarming, and for 20 min during the initial normothermic reperfusion period; group 6 was cold perfused without treatment (cold control). Functional indices and transient effects of 200μM bolus Ade (maximal vasodilation), and infusions of 1μM acetylcholine (Ach, endothelial dependent function), and 100μM NP (endothelial independent function) were compared before and after cold preservation.Results One hr after warm reperfusion, i.e., after 25 hrs, isovolumetric left ventricular pressure (LVP as a % of initial 100% control) was equivalent and greater in groups 3 (77±3% (SEM) and 4 (73±3%) than in groups 5 (53±6%) and 6 (2.3±5%); LVP was similar in groups 1 (85±3%) and 2 (81±2%) after 5 hrs. Before cold perfusion coronary flow (CF) increased similarly in all 6 groups with Ade (200±3%), Ach (120±3%) and NP (130±3%); 1 hr after warm reperfusion baseline CF was greater in groups 3 (81±3%) and 4 (84±2%) than in groups 5 (68±3%) and 6 (53±3%); CF was higher in group 1 (104±2%) than in group 2 (72±1%). CF responses after warm reperfusion in groups 1–6, respectively, were: 176±4, 130±2, 115±3, 109±2, 93±3, and 80±5% for Ade; 123±f 5, 105±2, 69±3, 73±3, 70±3, and 57±3% for Ach; and 123±4, 111±2, 86±3, 88±4, 91±4, and 73±4% for NP.Conclusions After long-term hypothermic perfusion with normal extracellular solution, flow responses to endothelium dependent, independent and mixed vasodilators are severely blunted. In part, this may be due to reduced baseline flow following normothertnic reperfusion because infusion of BDM during hypothermia, with infusion of NP plus Ade or NBTI during normothermic reperfusion, improves CF responses to both endothelium dependent and independent vasodilators.

ISSN:1062-3329    

DOI:10.3109/10623329409024637

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

We tested the effect of brief intraluminal perfusion of rat aortas with 5 mM hydrogen peroxide (H2O2) on basal and stimulated endothelium-dependent relaxation. Both 10min perfusion with H2O2and pharmacologic inhibition of endothelium-derived relaxing factor/ nitric oxide (EDRFINO) by 100μM Nω-nitro-L-arginine increased the sensitivity to the vasoconstrictor phenylephrine 10-fold, consistent with a reduction in basal EDRF/NO. Paradoxically, 10 min perfusion with H2O2enhanced sensitivity to both the endothelium-dependent dilator acetylcholine (3-fold reduction in EC50), and the endothLelium-independent dilator sodium nitroprusside (5-fold reduction in EC50), while more prolonged exposure to H2O2selectively reduced endothelium-dependent relaxation. These resullts suggest differential sensitivity of basal and stimulated EDRF/NO to oxidative stress, and further that inhibition of basal EDRF/NO by H2O2enhances the activity of both endothelium-dependent and -independent vasodilators, consistent with functional antagonism between basal and stimulated EDRF/NO.

ISSN:1062-3329    

DOI:10.3109/10623329409024638

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

To investigate if anti-hypertensive drug therapy is effective in correcting the altered endo-thelial responses observed in blood vessels of DOCA-salt hypertensive rats, cumulative concentration-effect curves to noradrenaline, acetylcholine and sodium nitroprusside were constructed in rings of thoracic aortas with or without endothelium isolated from DOCA-salt hypertensive and control rats treated with hydralazine for 24 h (acute) or 15 d (chronic). Effective concentrations (EC50s) and maximal responses were analysed. Blood pressures of both control and DOCA-salt hypertensive rats decreased within 24 h to levels at or below those obtained before treatment and were maintained at reduced levels during the remainder of the treatment period (15 d). In preparations with endothelium, lower EC50s for noradrenaline were observed in aortas from DOCA-salt hypertensive rats in comparison with corresponding controls except for hydralazine (15 d) -treated group. The maximal responses to noradrenaline did not differ significantly between the different groups Similar EC50s and maximal responses to noradrenaline were observed in preparations without endothelium from DOCA-salt hypertensive and corresponding control rats. After acute and chronic hydralazine treatment similar responses to acetylcholine were found. An increased sensitivity to sodium nitroprusside, an endothelium-independent vasodilator, was found 15 days after hydralazine treatment. We concluded that: a) the increased sensitivity to noradrenaline observed in aortic rings with endothelium from DOCA-salt hypertensive rats was not corrected by acute treatment; chronically administered hydralazine potentiated noradrenaline responses in control aortas, therefore it was not possible to conclude about the influence of the anti-hypertensive treatment on the potentiated response observed in hypertensive aortas; b) acute and chronic hydralazine treatments corrected the impaired endothelium-dependent relaxation observed in aortas of DOCA-salt hypertensive rats; c) acute hydralazine treatment did not alter the relaxing response of smooth muscle in DOCA-salt rats; however, the chronic treatment increased the sensitivity to sodium nitroprusside in aortas of DOCA-salt rats. Therefore, correction of the decreased response to acetylcholine might, at least partially, be due to an increased response of vascular smooth muscle to nitrovasodilators such as NO that is released by acetylcholine.

ISSN:1062-3329    

DOI:10.3109/10623329409024639

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor