摘要:

The aim of this study was to use periarterial manipulation to produce an atheroma-like neo-intima in rabbits and study resting blood flow and vascular responsiveness in vivo. One common carotid artery was enclosed in a silastic collar to induce a neo-intima similar to that of human early atherosclerosis, and carotid blood flow was measured periodically over 8 days in 8 conscious rabbits. The vasodilator responses to intravenous infusions of the endothelium-dependent vasodilator, acetylcholine, and glyceryl trinitrate were measured in each artery at 2 and 7 days after surgical placement of the collar, and again following infusion of the nitric oxide synthase inhibitor, N-nitro-L-arginine (NOLA, 15 mg/kg). Histological examination of the arterial segments at completion of the study revealed significant intimal thickening of the regions of artery enclosed in the collar. Resting blood flow was lower in the collared vascular bed as compared with the control, from as early as 2 days after surgery. Acetylcholine- and glyceryl trinitrate-induced decreases in carotid resistance, however, were no different between the arteries after 2 days. At 7 days after surgery, the vasodilator response to acetylcholine was significantly impaired in the collared vascular bed when compared with the control, while the glyceryl trinitrate-induced vasodilatation was similar in the two beds. Following NOLA infusion, mean arterial pressure was significantly increased and blood flow through both arteries was reduced. After NOLA, acetylcholine-induced vasodilatation in the collared vascular bed was no longer different from the vasodilatation in the control bed. Therefore, a developing neo-intima reduces the blood flow through the collared carotid artery before any morphological changes are detected. These results suggest that the nitric oxide-mediated dilator function of resistance vessels distal to the developing lesion is compromised, in this study in the absence of hyperlipidaemia.

ISSN:1018-1172    

DOI:10.1159/000159043

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The role of cAMP-mediated pathway in modulating angiogenesis was investigated. We have shown previously that activators of protein kinase C (PKC) caused a marked increase in angiogenesis, while the specific inhibitor of PKC, Ro 318220 suppressed angiogenesis. Here we show that forskolin, which activates adenylate cyclase and elevates the intracellular levels of cAMP, and the Sp-diastereomer of adenosine cyclic-3’,5’-monophosphothioate (Sp-cAMPS), caused a dose-dependent suppression of collagenous protein biosynthesis and angiogenesis in the chick chorioallantoic membrane system (CAM). The opposite modulation of angiogenesis by activators of PKC and elevated cAMP levels was further confirmed by the suppression of 4β-phorbol-12-myristate-13-acetate (4β-PMA)-stimulated angiogenesis by either forskolin or Sp-cAMPS. On the contrary, the Rp-diastereomer of adenosine cyclic-3’,5’-monophospho-thioate (Rp-cAMPS), which antagonises endogenous cAMP biochemical actions, had no effect on angiogenesis alone and did not suppress 4β-PMA stimulated angiogenesis. However, Rp-cAMPS antagonised the effect of forskolin and Sp-cAMPS on 4β-PMA induced angiogenesis. Similar results were obtained in the human umbilical vein endothelial cell tube formation assay. In this system, the PKC inhibitor, Ro 318220, caused a dose-dependent inhibition and 4β-PMA reversed this effect. Also, forskolin and Sp-cAMPS caused an inhibition in tube formation. These results indicate that increased levels of intracellular cAMP have a negative effect in normal angiogenesis and cause a large reduction of the promotion of angiogenesis resulting from PK

ISSN:1018-1172    

DOI:10.1159/000159044

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Coronary neovascularization was studied following grafting of avascular hearts from gestation day-12 (E-12) rat embryos to the anterior eye chambers of adult rats. Volume densities (Vv) of vessels, myocytes, and the extracellular matrix (ECM) after 3–7, 14, 21, and 35 days in oculo were compared to Vv in hearts developing in utero at E-15, E-18, and E-20. The myocardium in both models exhibited similar vessel Vv and capillary developmental stages: (1) clustering of endothelial cells and red blood cells; (2) endothelial cell migration, and (3) tube formation/maturation. The Vv of myocytes increased while that of the ECM remained constant over time. Cross-species grafting utilizing species-specific antibodies determined that the majority, but not all, of the 10-day graft vasculature was of graft origin. Therefore, both de novo growth (vasculogenesis) and sprouting (angiogenesis) were occurring in oculo. Tracer molecules infused into host rats reached the outermost graft vessels only after 10 days in oculo, suggesting a functional link with the host circulation after this time. Thus, we have shown that both models exhibit similar: (1) vascular Vv; (2) shifts in Vv of nonvascular components; (3) stages of neovascularization, and (4) mechanisms of neovascularization. In conclusion, coronary neovascularization occurring in oculo closely mimics normal coronary vessel developmen

ISSN:1018-1172    

DOI:10.1159/000159045

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Desmopressin and vasopressin were injected into the blood supply of the bilaterally perfused nasal mucosa of the dog. Nasal vascular resistance and, in some experiments, nasal airflow resistance and the secretory output of the lateral nasal gland were measured on both sides. Systemic arterial blood pressure was recorded. Desmopressin caused a dose-related vasodilatation on the side of injection with no changes in systemic arterial blood pressure or secretion by the lateral nasal gland. Nasal airflow resistance did not change significantly. Vasopressin increased nasal vascular resistance on the side of injection with no changes in the systemic arterial blood pressure or secretion by the lateral nasal gland. Nasal airflow resistance did not change significantly. Thus desmopressin dilates the nasal vascular bed and vasopressin constricts it. The relevance of these findings to the use of the two agents applied in to the nose in clinical practice is discussed.

ISSN:1018-1172    

DOI:10.1159/000159046

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The effects of MK-801 on the cerebral arteries and the possible involvement of the endothelium in such a response were examined using two experimental approaches: in vivo, by recording cerebral blood flow (CBF) in the unanestheized goat, and in vitro, by recording isometric tension in goat and human cerebral arteries. Injection of increasing doses (3, 10, 30, and 100 µg) of MK-801 directly into the cerebroarterial supply elicited decreases in CBF and increases in cerebral vascular resistance (CVR; for the highest dose tested CBF decreased by 16 ± 10% and CVR increased by 18 ± 10%, p& < 0.05). Administration of MK-801 as a single intravenous bolus (0.2 mg kg–1) reproduced that vasoconstrictor response (CBF decreased by 17 ± 9% and CVR increased by 46 ± 33%, p < 0.05), and it was followed by a phase of sustained tachycardia (26 ± 15% increase in resting heart rate, p < 0.01) and hypertension (34 ± 17% increase in resting mean arterial blood pressure, p < 0.05). In the in vitro experiments, addition of cumulative concentrations (10-6 to 3 × 10-4M) of MK-801 elicited concentration-related contractions of goat and human cerebral arteries at both resting and active tone (10-5M prostaglandin F2α). The MK-801-elicited contractile response in goat cerebral arteries at resting tone (maximum contraction of 7.7 ± 5.5% of the response to 50 mM KCl) was enhanced during the following treatments: endothelium deprivation (16.3 ± 4.1%, p < 0.05); 10-5 and 10–4 M NG-nitro-L-arginine (NOLAG, 16.9 ± 9.1 and 33.2 ± 16.6% respectively, p& < 0.05), and 10-5M NOLAG + 10–4M L D-arginine (22.6 ± 7.1%, p < 0.05). However, 10-5M NOLAG + 10-4ML· arginine did not induce significant changes (11.0 ± 7.0%). These results demonstrate that: (1) MK-801 has a direct constrictor action on cerebral arteries, and (2) the endothelium plays a negative feedback role by counteracting the MK-801-elicited contractions through the release of nitric oxide or a nitric oxid

ISSN:1018-1172    

DOI:10.1159/000159047

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The morphological and growth characteristics of human macrovascular endothelial cells (ECs) from venous and arterial umbilical cord vessels and microvascular ECs from foreskin were compared during cultivation. By means of time-lapse microcinematography and phase-contrast microscopy, differences in cell morphology and migratory activity between the different types of ECs were found. Growth characteristics were dependent on the type of EC, the nature of the substrates on which the ECs were grown and the presence of growth factors. For all types of ECs optimal growth and formation of a monolayer were observed when the ECs were cultured on fibronectin or gelatin substrates in the presence of EC growth factor and heparin. Under these conditions confluent cultures of macrovascular ECs reached maximal cell densities of 1,400–1,900 ECs/mm2, whereas microvascular ECs reached maximal cell densities of about 700–900 ECs/mm2. The cell cycle times calculated from the population-doubling time and the stathmokinetic index, respectively, amounted to 63 and 83 h for microvascular ECs, 33 and 35 h for venous macrovascular ECs, and 29 and 35 h for arterial macrovascular

ISSN:1018-1172    

DOI:10.1159/000159048

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The effects of hyper- and hypotonic solutions on vascular smooth muscle were studied using helical strips from human umbilical arteries. Hypertonic solutions evoked a biphasic contraction that consisted of early and late contractions. Verapamil or Ca2+-free conditions inhibited early contraction induced by tonicity of 340-539 mosm/kg. Under these conditions, late contraction induced by 340-407 mosm/kg was inhibited, whereas contraction induced by 539 mosm/kg was not. Hypotonic solutions evoked a monophasic contraction. Verapamil or Ca2+-free conditions inhibited contraction induced by tonicity of 249-266 mosm/kg but not by tonicity of 213 mosm/kg. Hyper- or hypotonicity-induced contractions were not affected by the presence or absence of endothelium. These results suggest that a small increase or decrease in tonicity within the pathophysiological range of osmotic pressure (260–340 mosm/kg) evokes contraction in human umbilical arteries by stimulating calcium influx through voltage-sensitive Ca2+ channel

ISSN:1018-1172    

DOI:10.1159/000159049

出版商:S. Karger AG    

年代:1994

数据来源: Karger