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Monoclonal antibody of human serum apolipoprotein E in clinical application
J Mol Cell Cardiol 24 (Supplement I) (1992) p-02-32
m&FuzCN
Cw FTmanm
v+vxmm
TONUS By ~lINRATSWITHPCU%XUY
Takas,gi
Miyauchi’ l 2 , Rygsuke Yorikane’, Tateshi 2akurai’. Goro Yamada’, Tomoh 1 , Yasuro Sugishita and Katsutcshi Goto . Department of Phanmcology and rtment of Internal Medicine, Universitv of Tsukuba. Ibaraki 305. Janan ?!he present study was designed to investigate the pathophysi&$~l roles of endothelin-1 (W in rats with xmocrotaline (MCI-induced oulmonarv hwertension. Three weeks after subcutaneous injection of MC (60 r&kg). rats (k-rats. n=12) were sacrificed. Vehicle-injected rats (n=l2) were served as controls. The ring segment
of the isolated pulmonary artery (PA) or the aorta was suspended in Krebs solution Venous plasma concentrations of ET were measured by a and tension was measured. sandwich-enzyme imrunoassay. The right ventricular pressure mrkedly elevated (58.0 + 4.7 Iman fr SEMI rmHg) in MC rats. ET produced a dose-dependent vasoconstriction on PA. The m2 values were significantly smaller in MC rats than in control rats (8.31 + 0.08 vs 8.75 + 0.09, p
vascular
in MC rats and in control rats. Plasma ET higher in MC rats than in control rats (5.08 + 0.69 Present findings indicate that the plasma levels of that the pulmonary vascular response to ET-l was it is suggested that the regulation of the pulmonary
tonus by endogenous Fp may be altered
in MC rats.
AND 8-Br-c?iMP p-02,33INHIBITION OF CHLORIDE CURRENT BY ISOPRENALINE, STAUROSPORINE IN ENDOTHELIAL CELLS Rikuo Department of Ochi, Seigo Ueda*, Tomoo Nunokawa, Arisa Ono. 113 Phys iology , Juntendo University School of Medicine, Hongo, Tokyo Hospital, and Cardiovascular Division, Tokyo Metropolitan Geriatric Itabashi, Tokyo 173*, Japan vascular Endothelial cells play a key role in the regulation of such as tone by releasing muscles modulators of vascular smooth endothelium-derived relaxing factor (EDRF/NO). Whole-cell clamp study of the cultured endothelial cells from bovine pulmonary artery revealed a depolarization-activated current mainly carried by Cl. The Cl conductance I-V curve at estimated from slope conductance of positive potentials was depressed to 41 + 16 % (n=Z.l) by isoprenaline (lOOOnM), to 34 + 19% (n=lO) by 8-Br-CAME (0.25mM) and to 34.4 + 16.1 induced a % by staurosporine (1000nM). The decrease in Cl current through hyperpolarization, which is expected to increase Ca influx The non-specific cation channels by increasing driving force. The increase in [Cali, thus produced, can activate NO synthase. result endothelial suggests that A-kinase and C-kinase systems in cells may regulate vascular tone by modulating the Cl conductance.
P-02-34RAT VENTRICULAR MYOCYTES MODULATE PROLIFERATION OF CARDIAC MICROVASCULAR ENDOTHELIAL CELLS. Masashi Nishida, Ralph A. Kelly, Thomas W. Smith. Harvard Medical School. Boston, MA 02146 USA. To examine cell-cell interaction in heart micro-circulation, we isolated ventricular myocytes (ARVM)
and cardiac
microvascular
endothelial
cells (CMEC)
from adult rat hearts and co-cultured
these two types of cells. As an index of endothelial cell proliferation, 3H-thymidine uptake and CMEC cell number were examined. When CMEC were co-cultured with ARVM, 3H-thymidine uptake into CMEC was augmented 2.5 times, as was cell number, compared to CMEC in monoculture. Expression of prepro ET-l and TGF-61 mRNA, growth regulatory factors for both myocytes and endothelial cells, were examined using Northern analysis. Although levels of expression of both prepro ET-1 and TGF-I31 messages were low in both cell types in primary mono-culture, co-culture of CMEC with ARVM markedly increased the expression of both prepro ET- 1 and TGF-RI mRNA. These results indicate that a dynamic and reciprocal interaction occurs between ARVM and CMEC in heterocellular primary culture, resulting in the generation of paracrine and autocrine cell-cell signalling mechanisms ihat could affect ca;diac mygcyte function and phenotype, and that could augment microvascular cell growth and -perhaps and . anaiogenesis -neovascularization in viva. S.165
m&FuzCN
Cw FTmanm
v+vxmm
TONUS By ~lINRATSWITHPCU%XUY
Takas,gi
Miyauchi’ l 2 , Rygsuke Yorikane’, Tateshi 2akurai’. Goro Yamada’, Tomoh 1 , Yasuro Sugishita and Katsutcshi Goto . Department of Phanmcology and rtment of Internal Medicine, Universitv of Tsukuba. Ibaraki 305. Janan ?!he present study was designed to investigate the pathophysi&$~l roles of endothelin-1 (W in rats with xmocrotaline (MCI-induced oulmonarv hwertension. Three weeks after subcutaneous injection of MC (60 r&kg). rats (k-rats. n=12) were sacrificed. Vehicle-injected rats (n=l2) were served as controls. The ring segment
of the isolated pulmonary artery (PA) or the aorta was suspended in Krebs solution Venous plasma concentrations of ET were measured by a and tension was measured. sandwich-enzyme imrunoassay. The right ventricular pressure mrkedly elevated (58.0 + 4.7 Iman fr SEMI rmHg) in MC rats. ET produced a dose-dependent vasoconstriction on PA. The m2 values were significantly smaller in MC rats than in control rats (8.31 + 0.08 vs 8.75 + 0.09, p
vascular
in MC rats and in control rats. Plasma ET higher in MC rats than in control rats (5.08 + 0.69 Present findings indicate that the plasma levels of that the pulmonary vascular response to ET-l was it is suggested that the regulation of the pulmonary
tonus by endogenous Fp may be altered
in MC rats.
AND 8-Br-c?iMP p-02,33INHIBITION OF CHLORIDE CURRENT BY ISOPRENALINE, STAUROSPORINE IN ENDOTHELIAL CELLS Rikuo Department of Ochi, Seigo Ueda*, Tomoo Nunokawa, Arisa Ono. 113 Phys iology , Juntendo University School of Medicine, Hongo, Tokyo Hospital, and Cardiovascular Division, Tokyo Metropolitan Geriatric Itabashi, Tokyo 173*, Japan vascular Endothelial cells play a key role in the regulation of such as tone by releasing muscles modulators of vascular smooth endothelium-derived relaxing factor (EDRF/NO). Whole-cell clamp study of the cultured endothelial cells from bovine pulmonary artery revealed a depolarization-activated current mainly carried by Cl. The Cl conductance I-V curve at estimated from slope conductance of positive potentials was depressed to 41 + 16 % (n=Z.l) by isoprenaline (lOOOnM), to 34 + 19% (n=lO) by 8-Br-CAME (0.25mM) and to 34.4 + 16.1 induced a % by staurosporine (1000nM). The decrease in Cl current through hyperpolarization, which is expected to increase Ca influx The non-specific cation channels by increasing driving force. The increase in [Cali, thus produced, can activate NO synthase. result endothelial suggests that A-kinase and C-kinase systems in cells may regulate vascular tone by modulating the Cl conductance.
P-02-34RAT VENTRICULAR MYOCYTES MODULATE PROLIFERATION OF CARDIAC MICROVASCULAR ENDOTHELIAL CELLS. Masashi Nishida, Ralph A. Kelly, Thomas W. Smith. Harvard Medical School. Boston, MA 02146 USA. To examine cell-cell interaction in heart micro-circulation, we isolated ventricular myocytes (ARVM)
and cardiac
microvascular
endothelial
cells (CMEC)
from adult rat hearts and co-cultured
these two types of cells. As an index of endothelial cell proliferation, 3H-thymidine uptake and CMEC cell number were examined. When CMEC were co-cultured with ARVM, 3H-thymidine uptake into CMEC was augmented 2.5 times, as was cell number, compared to CMEC in monoculture. Expression of prepro ET-l and TGF-61 mRNA, growth regulatory factors for both myocytes and endothelial cells, were examined using Northern analysis. Although levels of expression of both prepro ET-1 and TGF-I31 messages were low in both cell types in primary mono-culture, co-culture of CMEC with ARVM markedly increased the expression of both prepro ET- 1 and TGF-RI mRNA. These results indicate that a dynamic and reciprocal interaction occurs between ARVM and CMEC in heterocellular primary culture, resulting in the generation of paracrine and autocrine cell-cell signalling mechanisms ihat could affect ca;diac mygcyte function and phenotype, and that could augment microvascular cell growth and -perhaps and . anaiogenesis -neovascularization in viva. S.165