Endorthelium-modulated proliferation of medial smooth muscle cells: influence of angiotensin II and converting enzyme inhibition

This study investigated the role of the endothelium and angiotensin II (Ang II) in regulating medial smooth muscle cell (SMC) proliferation. [3II]-thymidine incorporation into medial SMC of rat arteries was examined in vivo, using ballooned rat carotid arteries, as well as in vitro, using cultures of aortic tissue rings (organoids). In vivo, maximal medial [3H]-thymidine incorporation occurred within 3 days post-ballooning. In endothelium-denuded organoids, maximum medial DNA synthesis was achieved after 7 days of culture. [3H]-thymidine-labelling of SMC in intact organoids (with endothelium) increased minimally during culture, indicating that the endothelium provided protection with respect to medial proliferation under basal conditions (culture in the presence of 1% plasma-derived serum). Inclusion of 10−7 M Ang-II significantly elevated medial [3H] thymidine incorporation above that in control cultures. The stimulatory effect of Ang II was much more pronounced in intact organoids than in endothelium-denuded organoids, indicating synergistic growth regulation by Ang II and endothelium-derived factors. When organoids were cultured in the combined presence of Ang II and the ACE inhibitor cilazaprilat, labelling indices of intact organoids were also significantly increased above control, but to a lower level than those obtained in the presence of Ang II alone. However, for endothelium-denuded organoids, medial [3H]-thymidine incorporation in the combined presence of Ang II and cilazaprilat was not significantly different from that in untreated controls. Thus, cilazaprilat exerts both endothelium-dependent and endothelium-independent negative regulatory effects on medial SMC proliferatio

Angiotensin-Induced Growth Related Metabolism Is Activated in Cultured Smooth Muscle Cells From Spontaneously Hypertensive Rats and Wistar-Kyoto Rats

Smooth muscle cells from spontaneously hypertensive rats (SHR) proliferate in culture faster than those isolated from sex- and age-matched Wistar- Kyoto (WKY) animals. There was no difference in the kinetics of S6 kinase activation in the two cultures, but later metabolic events associated with proliferation were stimulated earlier in SHR cells than in WKY, eg, activation of ornithine decarboxylase. Both cell types elaborated an extensive extracellular matrix in culture composed of a different blend of connective tissue macromolecules. Matrix material from SHR cells was more stimulatory to growth of WKY cultures than their own matrices. Angiotensin stimulated the growth and synthesis of extra-cellular matrix material in SHR more than in WKY derived vascular smooth muscle cell cul-tures. Am J Hypertens 1991;4:183-18

ANALISIS BANJIR RANCANGAN DENGAN METODE HSS NAKAYASU PADA BENDUNGAN GINTUNG

Jebolnya Situ Gintung merupakan akibat dari perubahan debit banjir yang terus bertambah. Hal tersebut perlu diana/isis terhadap debit banjir rancangan yang selanjutnya dapat digunakan untuk merencanakan Bendungan Gintung yang baru. Berdasarkan permasalahan di atas, maka perlu dikembangkan perhitungan banjir rancangan dengan metode HSS Nakayasu. Perhitungan dengan menggunaan data hujan. Pada penelitian ini digunakan 18 Pos stasiun penangkar hujan yang diseleksi menurut kelayakan data menjadi 9 pos stasiun hujan dengan memasukan nilai hujan harian maksimum tahunan. Data curah hujan yang disaring memilki tingkat kepercayaan yang rendah, namun masih masuk ke dalam data aman. Dalam penentuan debit banjir rencana terlebih dahulu dilakukan ana/isa frekuensi dan penetapan sebaran data curah hujan kemudian diuji dengan chi-kuadrat. Distribusi yang sesuai adalah distribusi Log Pearson Type III. Dari hasil ana/isa debit banjir rancangan, untuk merencanakan bendungan digunakan debit banjir kala ulang Ql000 = 289,348 m3/dt

Histamine, a vasoactive agent with vascular disrupting potential, improves tumour response by enhancing local drug delivery

Tumour necrosis factor (TNF)-based isolated limb perfusion (ILP) is an approved and registered treatment for sarcomas confined to the limbs in Europe since 1998, with limb salvage indexes of 76%. TNF improves drug distribution in solid tumours and secondarily destroys the tumour-associated vasculature (TAV). Here we explore the synergistic antitumour effect of another vasoactive agent, histamine (Hi), in doxorubicin (DXR)-based ILP and evaluate its antivascular effects on TAV. We used our well-established rat ILP model for in vivo studies looking at tumour response, drug distribution and effects on tumour vessels. In vitro studies explored drug interactions at cellular level on tumour cells (BN-175) and Human umbilical vein endothelial cells (HUVEC). There was a 17% partial response and a 50% arrest in tumour growth when Hi was combined to DXR, without important side effects, against 100% progressive disease with DXR alone and 29% arrest in tumour growth for Hi alone. Histology documented an increased DXR leakage in tumour tissue combined to a destruction of the TAV, when Hi was added to the ILP. In vitro no synergy between the drugs was observed. In conclusion, Hi is a vasoactive drug, targeting primarily the TAV and synergises with different chemotherapeutic agents

B?lahan or a Myth Dispelled

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