摘要:

Purposes of this study were to determine whether: (1) nitric oxide is involved in endothelium-dependent relaxation in helical strips of dog cerebral arteries; (2) relaxing factor distinct from NO is also involved, and (3) susceptibility to NG-nitro-L-arginine (L-NA), an NO synthase inhibitor, of the response to mediators liberating NO from the endothelium and nerve differs. Changes in isometric tension were recorded. In the strips contracted with prostaglandin F2α, substance P and arginine vasopressin produced a relaxation which was abolished or reversed to a contraction by endothelium denudation. The relaxations were not influenced by indomethacin but were suppressed dose-dependently by L-NA, as was the response to nicotine that stimulates the non-adrenergic, non-cholinergic vasodilator nerve and liberates NO. The inhibitions were reversed by L- but not D-arginine. NO (acidified NaNO2)-induced relaxations were not reduced by L-NA. The inhibitory effect was greater in the responses to vasopressin than substance P; however, there was no significant difference in the response to nicotine vs. the peptides. Substance P increased the level of cyclic guanosine monophosphate (GMP) in the artery strips with the intact endothelium, the effect being abolished by endothelium denudation, L-NA and oxyhemoglobin. Relaxations caused by adenosine triphosphate (ATP) and adenosine diphosphate (ADP) were dependent partially on the endothelium. Treatment with L-NA attenuated the ATP-induced relaxation in the strips with endothelium but did not alter the response of denuded strips. It may be concluded that endothelium-dependent relaxations caused by substance P, vasopressin, ATP and ADP in dog cerebral arteries are mediated solely via NO that activates guanylate cyclase and increases the production of cyclic GMP. Susceptibility to L-NA of NO synthase in the endothelium and vasodilator nerve does not appear to differ significantly

ISSN:1018-1172    

DOI:10.1159/000158976

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Mastoparan is a wasp venom peptide that activates G-proteins, certain classes of which are involved in the release of endothelium-derived relaxing factor (EDRF). In the present study, we investigated whether this peptide might be a useful tool with which to elucidate the signal transduction pathways responsible for EDRF release from pulmonary artery endothelium. Mastoparan (10-50 µg/ml) elicited an increase in endothelial cell cytosolic free calcium concentration ([Ca2+]i) and EDRF release in a concentration-dependent manner. Both effects were dependent on Ca2+ influx, as they were inhibited by removal of extracellular Ca2+. In addition, when endothelial cells were suspended in Ca2+-free buffer, mastoparan inhibited ATP-induced increases in [Ca2+]i, presumably by depleting intracellular Ca2+ stores. More importantly, mastoparan also caused the release of fura-2 from dye-loaded endothelial cells, unlike ATP, which did not affect fura-2 loss. These data indicate that although mastoparan may act on G-proteins to elicit release of Ca2+ from intracellular stores, the primary mechanism of action responsible for mastoparan’s ability to elicit EDRF release is an increase in cell membrane permeability followed by an influx of extracellular Ca2+

ISSN:1018-1172    

DOI:10.1159/000158977

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

This paper describes a new technique for determining the intravascular pressure at the base of mesenteric arcades (arterial diameter less than 200 µm) in conscious, unrestrained, resting rats, using this technique we found that under Brietal anaesthesia, shortly after implanting the catheters, the pressure in the base of the arcades (Pmes) was 86% of systemic pressure (Psys). After recovering from the anaesthetic, 6-8 h later, while Psys rose from average 79 to 114.5 mm Hg, Pmes /Psys fell to 69%. By contrast, when anaesthesia was induced, although Psys immediately fell by 44%, Pmes/Psys did not change. Acute pharmacological experiments in resting animals showed that the relative contribution of the arcade vessels to the peripheral resistance was variable. When serotonin was injected into the aorta, although Psys was unaffected, Pmes/Psys fell from 67 to 27%. Conversely, with noradrenaline, Psys rose by 30%, but Pmes/Psys remained unchanged. Angiotensin-II showed a third pattern, where Psys increased by 38%, but Pmes/Psys rose transiently to 86%. The data suggest that in the rat mesenteric bed, under conscious conditions, the arcade arteries can contribute substantially to the control of peripheral resistance

ISSN:1018-1172    

DOI:10.1159/000158978

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

There is considerable controversy regarding whether angiotensin II (AngII) stimulates hypertrophy or hyperplasia of vascular smooth muscle cells (SMC). The purpose of the present study was to determine whether stretch of the vessel wall or AngII treatment increased protein or DNA synthesis in intact aortic rings in vitro and whether stretch of the vessel wall altered the growth responses to AngII. Rat aortic rings were mounted on steel supports in serum-free medium for 16 h and subjected to 0 or 1.5 g of preload (i.e. passive stretch). Fetal bovine serum (13%, FBS) or AngII [1 µM, in the presence or absence of an angiotensin receptor antagonist, losartan (DuP753) 10 µM] was administered and isometric tension development was measured. 35S-methionine (3 µCi/ml) was added to the baths at 14-16 h for measurement of protein synthesis. Passive stretch did not increase protein synthesis as compared to vessels mounted under no-preload conditions. AngII and FBS elicited similar increases in isometric tension development, but tension development in FBS-treated rings was sustained 4 times longer than in rings treated with AngII. AngII and FBS increased protein synthesis by 35 and 121%, respectively, but there was no difference in the extent of contractile agonist-induced protein synthesis between rings subjected to 0 or 1.5 g of passive stretch. Losartan totally abolished AngII-induced tension development and protein synthesis. AngII and FBS did not stimulate increased DNA synthesis in aortic rings, as measured by 3H-thymidine incorporation. These results suggest that AngII stimulates hypertrophy rather than hyperplasia of fully contractile SMC in an intact vess

ISSN:1018-1172    

DOI:10.1159/000158979

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

A radioligand binding assay and autoradiographic localisation of P2χ-purinoceptors were carried out in several different blood vessels from rat, guinea-pig and rabbit by using [3H]α, β-methylene ATP ([3H]α, β-MeATP) as the radioligand. The radioligand binding assay on rabbit ear artery showed that the binding process was saturable, and a high density of P2x-purinoceptors was observed. Autoradiographic localisation showed that the specific [3H]α, β-MeATP binding sites were only associated with the smooth muscle of the blood vessels. Semi-quantitation of the autoradiographs revealed significant differences in the densities of P2x-purinoceptors amongst the vessels studied. Generally the medium- and small-sized arteries had higher densities of P2x-purinoceptor than the elastic and large muscular arteries. In some large muscular arteries, such as the rabbit carotid, renal, hepatic and mesenteric, the outer region of vessel had a higher density of receptors than the inner region. The veins in this study were sparsely labelled, except portal veins where the longitudinal and circular layers of muscles were found to have different densities of P2x-purinoceptors. The results from this study provide direct evidence for the existence of P2x-purinoceptors in blood vessels; furthermore, the distribution of the P2x-purinoceptors is consistent with known pharmacological responses elicited by ATP in these v

ISSN:1018-1172    

DOI:10.1159/000158980

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Blood vessels in the anterior region of the knee joint of anaesthetised rabbits showed a biphasic response to the electrical stimulation (10 Hz, 1 ms width, 10 V amplitude) of nerve fibres supplying the knee, as measured by laser Doppler flowmetry. The response consisted of vasoconstriction during nerve stimulation followed by a prolonged dilatation. The vasoconstrictor response was mediated by noradrenaline acting mainly via α1-adrenoceptors as it was substantially reduced by close intra-arterial injection of the α-adrenergic antagonist phentolamine (∼50% reduction) and the selective α1-adrenergic antagonist prazosin (∼50% reduction) but not by the α2-antagonist rauwolscine. Further studies involving prolonged (2-hour) close intra-arterial infusion of prazosin gave a ∼ 50% reduction of the constrictor response with a concentration of 10-5M and ∼95% reduction when the concentration was raised to 10-4M. At the higher prazosin concentration responses to close intra-arterial injection of the α1-agonist phenylephrine were substantially reduced but responses to the α2-agonists clonidine and UK-14304 were not significantly influenced. Infusions of the α2 antagonist CH 38083 failed to inhibit nerve-mediated vasoconstriction at 10-5 or 10-4M. There did not appear to be a purinergic component, as the constrictor response was unaffected by the P2x desensitiser αβ-methylene adenosine 5’-triphosphate. The dilator response appeared to be mediated principally by substance P (presumably released from sensory C fibers) as it was substantially reduced by intra-articular injection of substance P antagonist D-Pro4D-Trp7,9,10-SP(4-ll). These results indicate that in the anterior region of the rabbit knee joint α-adrenoceptors mediate vasoconstriction during electrical stimulation of the nerve supply to joint blood vessels and suggest that the neurotransmitter is likely to be noradrenaline. The dilator response may arise from activation of sensory (C) nerve fibres containing substance P which could have a patho-physiological role in inflamm

ISSN:1018-1172    

DOI:10.1159/000158981

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Medial smooth muscle cell migration and neointimal proliferation are primary contributors to the delayed restenosis that occurs after percutaneous transluminal coronary angioplasty. In this study, we describe the antiproliferative and antichemotactic properties of U-67154, the parent compound of a series of novel aminochromones, determined using in vitro fibroblast and smooth muscle cell culture systems. U-67154 inhibited the induction of DNA synthesis in confluent BALB/c 3T3 fibroblasts and early-passage rat aortic smooth muscle cells by several different growth factors in a concentration-dependent manner. U-67154 similarly inhibited the proliferation of these cells stimulated by serum. Growth-factor-induced chemotaxis of fibroblasts and early-passage rat aortic smooth muscle cells also was inhibited by U-67154 in a concentration-dependent manner. The IC50S for all of these functions were similar (between 120 and 200 µM). Such antiproliferative and antichemotactic effects did not result from cytotoxicity (as measured by lactate dehydrogenase release, neutral red uptake or nonspecific inhibition of protein synthesis). Most important, inhibition of long-term proliferation of fibroblasts and early-passage smooth muscle cells by U-67154 was fully reversible upon removal of the drug. Thus, U-67154 represents a class of novel, noncytotoxic compounds that may prove useful in the treatment of proliferative disorders such as delayed restenosis after percutaneous transluminal coronary angioplasty

ISSN:1018-1172    

DOI:10.1159/000158982

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Protein kinase C is known to influence contraction in vascular smooth muscle cells by Ca2+-dependent and Ca2+-independent mechanisms. In the present study, the effect of protein kinase C activation by phorbol 12-myristate 13-acetate on resting cytosolic free Ca2+ and on cellular Ca2+ pools was assessed in cultured rat aortic muscle cells using fura 2. Cellular Ca2+ pools were evaluated with the selective inhibitor of the sarcoplasmic Ca2+ ATPase, thapsigargin. In normotensive vascular smooth muscle cells, protein kinase C activation caused a redistribution of Ca2+ from the thapsigargin-sensitive pool into the cytoplasm, whereas, in hypertensive cells, no significant effect of protein kinase C activity on cellular Ca2+ distribution was found. It is concluded that protein kinase C modulates the amount of Ca2+ stored in the thapsigargin-sensitive calcium stores. In hypertensive cells, the regulation of Ca2+ pools by protein kinase C is disturbed.

ISSN:1018-1172    

DOI:10.1159/000158983

出版商:S. Karger AG    

年代:1993

数据来源: Karger

ISSN:1018-1172    

DOI:10.1159/000158984

出版商:S. Karger AG    

年代:1993

数据来源: Karger

ISSN:1018-1172    

DOI:10.1159/000158985

出版商:S. Karger AG    

年代:1993

数据来源: Karger