摘要:

There is substantial evidence indicating that the study of cytoskeletal and cytocontractile protein composition in vascular smooth muscle cells (SMCs) can be valuable in tracing structural changes during vascular remodeling. Recent nucleic acid and protein investigations suggest that myosin can be used as a new specific marker for the identification of SMC phenotypes in some pathological conditions affecting the vascular wall. In view of this new information, it would seem timely to review the structural bases of myosin isoform expression in the vascular smooth muscle system as well as the factors involved in its regulation. A puzzling feature has arisen in recent studies on this topic: the presence of non-muscle myosin variants in SMCs during physiological and pathological vascular remodeling. In the response to injury caused by mechanical, chemical and hormonal factors in animals, characterized by proliferation and migration of vascular SMCs from the media to the intima, there is a partial or complete recapitulation of a myosin isoform pattern pertinent to developing vascular smooth muscle tissue. Analysis of myosin isoform content in the vascular wall also demonstrates that: (1) changes in SMC composition may occur independent of medial SMC migration into intima, and (2) the presence of fetal-type SMCs in the neointima is not necessarily related to specific positional changes of medial SMCs.

ISSN:1018-1172    

DOI:10.1159/000159033

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Vascular smooth muscle tone is dependent on oxidative metabolism, a phenomenon of potential importance for the metabolic regulation of blood flow to tissues. The response of the rat portal vein to inhibition of cell respiration by cyanide (0.1-1 mM) is a reduction of its spontaneous myogenic activity. The trains of action potentials triggering phasic contractions are reduced in duration, while the frequency of trains is often somewhat increased as the resting membrane potential in the intervals between spike trains is less negative by 6.5 mV. Glibenclamide (10-7 M) did not affect the resting membrane potential or spontaneous mechanical activity of oxygenated portal veins, but partly restored the depressed myogenic activity in the presence of cyanide (0.5 mM). The spike trains were longer, while the membrane was depolarized by 3 mV compared with the effects of cyanide alone. Inhibition of both oxidative and glycolytic metabolism by 2 mM NaCN in a medium where glucose was replaced by β-hydroxybutyrate caused a hyperpolarization which was abolished by 10–7M glibenclamide. The relaxing effect of the K+ channel opener cromakalim (5· 10–9 to 6.25· 10–7M)was partly antagonized by glibenclamide. Basal cytosolic [Ca2+] was increased by cyanide, while the Ca2+ transients associated with phasic contractions were reduced in duration. This latter effect was partially reversed by glibenclamide. The effect of cyanide on high-K+ contractures, which are associated with sustained membrane depolarization and not dependent on repetitive spike activity, was not influenced by 10–7 M glibenclamide. The effects of inhibited cell respiration on spontaneous electrical activity seem to reflect a depolarizing drive caused by inhibited active ion exchange mechanisms, modified by a repolarizing drive, possibly from ATP-regulated K+ channels, causing reduced duration of the spike trains. While glibenclamide affects spontaneous activity at all levels of oxidative blockade, glibenclamide-sensitive hyperpolarization is seen only when both oxidative and glycolytic metabolism is

ISSN:1018-1172    

DOI:10.1159/000159034

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The effects of acetylcholine (ACh) and A23187 on ring preparations from the human umbilical artery (HUA) were investigated and compared with the rat aorta (RA). The results from the HUA demonstrate that: (1) At both high (pO2 600 mm Hg) and low O2 tension pO2 < 55 mm Hg), ACh and A23187 relaxed precontracted rings in a concentration-dependent and endothelium-independent manner. Changes in pO2 did not influence the responses of the HUA to either relaxant. (2) Relaxation responses of the HUA to either ACh or A23187 were insensitive to methylene blue (50 µM), L-nitro-arginine methyl ester (100 µM), indomethacin (10 µM)and nordihydroguaiaretic acid (50 µM). Relaxations initiated by ACh were also atropine-resistant. (3) Meclofenamic acid (3 µM) suppressed the relaxations to A23187, but not ACh. (4) Regardless of pO2 superoxide dismutase (100 U/ml) potentiated the relaxant effects of ACh, whereas mannitol (60 mM) enhanced ACh-initiated relaxations at high but not low pO2. (5) Ouabain (30 nM), high potassium (HK+, 60 mM) and tetraethylammonium (20 mM) inhibited responses to ACh. (6) Na+-free physiological saline solution inhibited both relaxations and oscillations initiated by either ACh or A23187. (7) Both nitroglycerin and exogenous nitric oxide (NO) fully, and 8-bromoguanosine 3’,5’-cyclic monophosphate partially, relaxed the HUA, and LY83583 (10 µM) reversed such relaxations. (8) In the RA, relaxation responses to ACh and A23187 were endothelium-dependent and sensitivity was reduced under high versus low pO2 conditions. We conclude that in the HUA, unlike in the RA, ACh and A23187 mediate their responses via an endothelium- and NO-independent processes), perhaps involving the release of a muscle-derived relaxing factor. ACh-initiated relaxations are mediated by activation of Na+, K+-ATPase, and subsequent hyperpolarization via K+ efflux, whereas A23187-mediated relaxations result from the synthesis of an indomethacin-resistant cyclooxygenas

ISSN:1018-1172    

DOI:10.1159/000159035

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

We have studied the influences of atherosclerosis, age and sex on arterial responsiveness to vasoactive agents using male and female Watanabe heritable hyperlipidaemic (WHHL) rabbits (4–12 months, n = 36) as a model for atherosclerosis and sex- and age-matched New Zealand White (NZW) rabbits (n = 36) as controls. The responses of isolated rings of basilar arteries mounted in organ baths to vasoactive substances were studied. KCl-induced contractions in female atherosclerotic rabbits were greater than controls but those of male atherosclerotic rabbits were equivalent to the respective controls. Age did not influence KCl-induced contractions of rabbits of either strain or sex. Histamine-induced contractions increased with age in female atherosclerotic rabbits only. Acetylcholine (ACh)-induced relaxations of 6-month-old male and female atherosclerotic rabbits were greater than their respective controls. ACh-induced relaxations of female but not male NZW rabbits decreased with age. Calcitonin gene-related peptide- and vasoactive intestinal polypeptide-induced relaxations in atherosclerotic male and female rabbits were not affected by age. However, relaxations of female but not male control rabbits decreased with age. These findings suggest that there are subtle changes in the control of vascular tone which develop with the onset and progression of atherosclerosis. Of particular significance is the increase in endothelium-dependent relaxation in WHHL rabbits. Sexual dimorphism in vascular reactivity is also indicated by (1) the increase in contractility in female but not male WHHL rabbits and (2) the age-dependent decrease in endothelium-dependent and endothelium-independent relaxation in female but not male control (NZW) rabbits that is coincident with the onset of sexual maturit

ISSN:1018-1172    

DOI:10.1159/000159036

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Recent research in ultrasound technology has led to the development of a high-resolution echo-tracking device. The present study was performed to evaluate the accuracy in the measurement of human radial artery intima-media thickness with this new device. We determined the correlation between histological and ultrasonic measurements of intima-media thickness in 15 radial artery segments obtained from the distal end of the wrist-elbow harvest for coronary bypass grafting in patients with coronary heart disease. For arterial intima-media thickness, a positive correlation was observed between ultrasonic and histological measurements (r = 0.618; p& < 0.014), and the difference between ultrasound and histology measurements was 41 ± 66 µm, with the higher measurements found by the ultrasonic device. In a subgroup of 11 patients, we determined the correlation between in vivo ultrasonic measurements of radial artery intima-media thickness at the preoperative stage and in vitro ultrasonic measurements of intima-media thickness obtained postoperatively in the same arterial segments. Internal diameter was larger in vivo than in vitro, and intima-media thickness was smaller in vivo than in vitro. The cross-sectional area of the arterial wall was calculated from internal diameter and intima-media thickness. In vitro wall cross-sectional area was correlated with in vivo wall cross-sectional area (r = 0.929; p& < 0.0001). Repeatability of in vivo intima-media thickness measurements was investigated in 10 subjects through the calculation of the repeatability coefficient as defined by the British Standards Institution. Intraobserver repeatability coefficient (comparison of two determinations, separated by a 10-min interval, obtained by the same observer) was 48.7 µm. These results indicate that the radial artery intima-media thickness can be accurately measured in huma

ISSN:1018-1172    

DOI:10.1159/000159037

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The role of cAMP-dependent protein kinase (PKA) in the relaxation of vascular smooth muscle by cAMP analogs was studied. The analog N6,2’-O-dibutyryl-cAMP (dbu-cAMP) reduced KC1- and phenylephrine (PE)-induced tension in rat aortic rings in a dose-dependent fashion (10–100 µM). Conversely, incubation with 8-bromo-cAMP (8Br-cAMP; 10-100 µM)had very little effect on tension. The soluble and particulate PKA activity was determined in the analog-treated, PE-contracted tissue. Interference from extracellular analogs was eliminated by washout of analog prior to homogenization of the tissue for the PKA assay and by the addition of charcoal (10 mg/ml) to the homogenization buffer. The nonrelaxant analog 8Br-cAMP significantly increased the activity ratio of soluble PKA at a concentration of 30 µM and, in the particulate fraction, increased the activity ratio at 30- and 100 µM. Total PKA activity in the soluble fraction was significantly decreased by all concentrations of 8Br-cAMP used (10, 30, 100 µM). The relaxant analog dbu-cAMP had no significant effect at any concentration on catalytically active or total PKA activity levels. The only effect seen, at 30 µM, was an increase in the particulate activity ratio, and this was smaller than that seen with 8Br-cAMP. The basis for the alteration in PKA activity by 8Br-cAMP was a decrease in total soluble PKA activity as opposed to an increase in free catalytic PKA subunit. The fall in total activity was most likely due to adsorption by charcoal of catalytic subunit released from the 8Br-cAMP-activated holoenzyme. Thus, under the conditions used to assay PKA activity in cAMP-analog-treated vascular tissue, a decrease in total PKA activity represents an activation of the enzyme and, in fact, appears to be a better indicator of activation than changes in activity ratios. In either case, activation of soluble and particulate PKA by cAMP analogs did not correlate with relaxation of rat aor

ISSN:1018-1172    

DOI:10.1159/000159038

出版商:S. Karger AG    

年代:1994

数据来源: Karger