摘要:

A characteristic of vascular smooth muscle cell morphology is a close apposition of its peripheral sarcoplasmic reticulum (SR) with the sarcolomma; this arrangement gives rise to important functional interactions whereby the peripheral SR regulates Ca2+ influx and vascular tone. We review here the key evidence supporting the following aspects of SR-sarcolemma interactions while establishing a conceptual framework encompassing (i) the SR ultrastructure and functions, (ii) the integration of the sarcolemmal Na+-Ca2+ exchanger and the peripheral SR in the mediation of a bidirectional Ca2+ exchange between the peripheral SR and the extracellular space, (iii) the existence of a higher myoplasmic free Ca2+ concentration [Ca2+]myo in the sub sarcolemmal space formed between the sarcolemma and the peripheral SR relative to the [Ca2+]myo of the inner myoplasm in the resting smooth muscle cell, (iv) the division of the sub sarcolemmal space into functional microdomains, (v) the existence of spontaneous localized bursts of Ca2+ release from the peripheral SR (Ca2+ sparks) towards the sarcolemma, (vi) the physiological triggering of nonlocalized Ca2+ release from the peripheral SR by Ca2+ influx (Ca2+-induced Ca2+ release), and (vii) capacitative Ca2+ entry in vascular smooth muscle. We present an overview of the physiological and pathological implications of these interactions.

ISSN:1018-1172    

DOI:10.1159/000159242

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

In porcine coronary artery, bradykinin-induced endothelium-dependent vasodilatations are associated with simultaneous endothelium as well as endothelium-dependent smooth muscle cell (SMC) hyperpolarizations. In contrast, in porcine ciliary artery bradykinin evokes endothelium-dependent relaxations, but no change in SMC membrane potential. This study addresses the question of whether the lack of bradykinin-induced SMC hyperpolarization is also associated with an absence of endothelial hyperpolarization in porcine ciliary artery. With a microelectrode to impale cells in arterial strips, a 12-mV transient bradykinin-induced hyperpolarization was measured in endothelial cells. Bradykinin evoked no SMC hyperpolarization deep in the media. Only occasionally, a slight 4-mV hyperpolarization could be recorded in some SMC next to the endothelium. The endothelial intracellular injection (through the recording electrode) of the fluorescent tracers, lucifer yellow or ethidium bromide, showed the existence of a heterocellular dye coupling between endothelial cells and SMC. These observations in porcine ciliary artery demonstrate that the lack of bradykinin-induced endothelium-dependent SMC hyperpolarization is not due to an absence of endothelial cell hyperpolarization, but most likely to an insufficient electrotonic propagation space constant from endothelial cells to SMC, despite the presence of a dye coupling between these cells.

ISSN:1018-1172    

DOI:10.1159/000159243

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

This study set out to examine in detail the distribution of axons of sympathetic non-noradrenergic neurons innervating the arterial bed in skeletal muscles of the forelimb and hindlimb of guinea-pigs. The distribution of non-noradrenergic axons with immunoreactivity to vasoactive intestinal peptide (VIP) was examined in limb muscles of different histochemical character. The immunohistochemical demonstration of myosin heavy chain from fast-twitch muscle, and the histochemical demonstration of adenosine triphosphatase and succinic dehydrogenase, were used to determine the muscle fibre profile of 6 different limb muscles. Muscles included the oxidative type I muscle fibre-rich accessory semimembranosus muscle, the predominantly glycolytic type II muscle fibre-rich cranial gracilis and biceps brachii muscles and the plantaris, gastrocnemius medial head and triceps brachii long head of mixed muscle fibre composition. The frequency with which the VIP-immunoreactive (VIP-IR) axons innervated intramuscular arterial vessels was compared between categories of muscles defined by their muscle fibre profile. This study demonstrated that the projection of non-noradrenergic sympathetic neurons to skeletal muscle vasculature was widespread in guinea-pig limb muscles, but that it was not uniform. VIP-IR axons were more likely to innervate the arterial vasculature of muscles with a high proportion of type I and/or oxidative muscle fibres than of muscles with a large proportion of type lib muscle fibres. This relationship between the distribution of sympathetic non-noradrenergic axons and the metabolic characteristics of muscle suggests that these presumed vasodilator neurons have an important role in matching blood flow to the particular metabolic demands of different limb muscles.

ISSN:1018-1172    

DOI:10.1159/000159244

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Coronary bypass vessels, saphenous vein (SV) and internal thoracic artery (ITA), differ in susceptibility to atherosclerosis and medium- to long-term patency. Whereas most ITA remain patent (90% at 10 years), 20% of SV grafts fail in the first year and ∼ 45% fail within 10 years. Reasons for these differences are not fully understood. Loss of SV patency may reflect early metabolic events, particularly increased proteoglycan (PG) synthesis which contributes to intimal volume and promotes atherogenesis through retention of atherogenic lipoproteins. We determined, in vitro, the PG metabolic activity of SV, ITA, and human coronary arteries through autoradiographic detection of incorporated [3100 µm). Increased subendothelial labelling in SV was due to increased PG synthesis, not decreased degradation. ITA showed no propensity for upregulation of subendothelial PG synthesis. Immunohistochemistry showed TGF-β 1 and TGF-β 2 localised primarily to the subendothelial zone of SV and coronary arteries. With time in culture immunostaining increased in parallel with increased PG synthesis. Subendothelial TGF- β 1 and TGF-β 2 were absent in ITA. A panspecific TGF- βneutralising antibody reduced subendothelial PG synthesis in SV and coronary arteries by 50 and 60%, respectively. These results support the idea that vessels susceptible to atherosclerosis show increased accumulation of subendothelial PG mediated b

ISSN:1018-1172    

DOI:10.1159/000159245

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

We have previously shown that human leukaemia inhibitory factor (hLIF) inhibits perivascular cuff-induced neointimal formation in the rabbit carotid artery. Since nitric oxide (NO) is a known inhibitor of smooth muscle growth, NO synthase (NOS) activity in the presence of hLIF was examined in vivo and in vitro. In rabbit aortic smooth muscle cell (SMC) culture, significant NOS activity was observed at 50 pg/ml hLIF, with maximal activity at 5 ng/ml. In the presence of the NOS inhibitor L-NAME, hLIF-induced activation of NOS was greatly decreased, however it was still 63-fold higher than in control (p& < 0.05). SMC-DNA synthesis was significantly reduced (-47%) following incubation with hLIF plus L-arginine, the substrate required for NO production (p& < 0.05), with no effect observed in the absence of L-arginine. Silastic cuff placement over the right carotid artery of rabbits resulted in a neointima 19.3 ± 5.4% of total wall cross-sectional area, which was increased in the presence of L-NAME (27.0 ± 2.0%; p& < 0.05) and reduced in the presence of L-arginine (11.3 ± 2.0%; p& < 0.05). The effect of L-arginine was ameliorated by co-administration of L-NAME (16.4 ± 1.5%). However, administration of L-NAME with hLIF had no effect on the potent inhibition of neointimal formation by hLIF (3.2 ± 2.5 vs. 2.1 ± 5.4%, respectively). Similarly, with hLIF administration, NOS activity in the cuffed carotid increased to 269.0 ± 14.0% of saline-treated controls and remained significantly higher with co-administration of L-NAME (188.5 ± 14.7%). These results indicate that hLIF causes superinduction of NO by SMC, and that it is, either partially or wholly, through this mechanism that hLIF is a potent inhibitor of neointimal formation in vivo and of smooth muscle proliferation i

ISSN:1018-1172    

DOI:10.1159/000159246

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Calcification of the elastic arteries of the young rat by treatment with vitamin D and nicotine (VDN) has been proposed as an animal model of arterial calcification associated with age and age-related vascular pathology in man. The calcium-binding protein, S-100, which is found in human atherosclerotic lesions was associated with medial calcification of the aorta in VDN rats, especially in cases of severe calcification. Calcification (total calcium content: 366 ± 87, n = 12 in VDN vs. 24 ± 2 µmol g–1 aortic dry weight in controls, n = 13) involved elastocalcinosis leading to elastolysis as revealed by a fall in the amount of desmosine and isodesmosine in the aortic wall (266 ± 17 and 254 ± 15 in VDN vs. 655 ± 56 and 588 ± 30 µg g–1 aortic dry weight in controls). The decrease in elastin was associated with an increase in the stiffness of the aortic wall (elastic modulus: 15.1 ± 1.8 in VDN vs. 6.7 ± 0.5 106 dyn cm–2in controls), an increase in end-systolic stress (central systolic aortic pressure: 152 ± 6 in VDN vs. 136 ± 2 mm Hg in controls) (at a normotensive mean pressure level) and left ventricular hypertrophy (heart weight/body weight 2.51 ± 0.10 in VDN vs. 2.24 ± 0.07 g kg–1 in controls). In conclusion, the mechanisms and consequences of aortic calcification in VDN show several similarities with calcification occurring in human athero-

ISSN:1018-1172    

DOI:10.1159/000159247

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Tissues are often cold stored for physiological studies and for clinical transplantation. We report that cold storage induces a relaxation to reoxygenation after hypoxia (H/R) in de-endothelialized porcine coronary arteries. In fresh denuded arteries stimulated with U46619, H/R did not elicit relaxation. However, after overnight cold storage (4°C), H/R elicited a transient relaxation with peak relaxation of 56 ± 8% (n = 8), which was reproducible after 2 days of cold storage. The H/R relaxation was inhibited by methylene blue (10 µM) and LY83583 (10 µM), O2-hemoglobin (1 µM), or NG-methyl-L-arginine (0.2 mM), but neither NG-nitro-L-arginine (0.2 mM) nor cyclo-oxygenase inhibition was effective. Importantly, the H/R relaxation was attenuated by KCl (40 mM) or tetrabutylammonium chloride (5 mM), a non-selective inhibitor of K+ channels. Interestingly, authentic nitric oxide (NO)- or S-nitroso-N-acetylpenicillamine (SNAP)-induced relaxations were enhanced by cold storage in U46619 (0.1 µM) contractures. When tissues were contracted with KCl (40 mM), the enhancement in NO- or SNAP-induced relaxation by cold storage was markedly smaller than with U46619. Neither catalase (1,200 U/ml) nor 3-amino-triazole (50 mM), an inhibitor of catalase, affected the H/R relaxation. The duration of H/R relaxation also increased with the period of incubation at 37 ° C in the organ bath. This was blocked by inhibition of NO synthesis or guanylate cyclase. Moreover, inhibition of protein synthesis with actinomycin D (0.1 µM) and cycloheximide (10 µM), or dexamethasone (1 µM), an inhibitor of NO synthase induction, blocked this increase in the duration of the H/R relaxation. The results suggest that in smooth muscle induction of NO pathway relaxation, which is in part mediated by K+ channels and inducible NO synthase, may be of importance to the understanding of ischemia/reperfusion responses in cold-stored

ISSN:1018-1172    

DOI:10.1159/000159248

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:1018-1172    

DOI:10.1159/000159249

出版商:S. Karger AG    

年代:1997

数据来源: Karger