Kuzu Jzole Pulmoner Arterlerinde Geli§en Hipoksik Pulmoner Vazokonstríksíyonda Give Gs Proteínierínín Rolü ^^
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Dosyalar
Tarih
2014
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Kafkas Univ, Veteriner Fakultesi Dergisi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Hipoksik pulmoner vazokonstriksiyon akcigerlerde ventilasyon perfüzyon dengesini saglayan fizyolojik uyum mekanizmasidir. Hipoksemi
ile seyreden progressif akciger hastaliklarmin patogenezinde önemli rol oynamakia birlikte saglikli bireylerde de görülmektedir. Yogun
çali5malara ragmen, hipoksik pulmoner vazokonstriksiyonun mekanizmasi henüz bulunamamijtir. G proteinleri vasküler endotel ve düz kas
hücrelerinde reseptör aracilikli sinyal iletimine aracilik ederek vasküler tonusun düzenlenmesinde önemli rol oynayan membrana bagli protein
ailesidir. Biz bu çalijmada, kuzu izole pulmoner arterierinde izlenen hipoksik vazokonstriksiyonun oluj mekanizmasinda G, ve G^ proteinlerlnin
rolünüsaptamayiamacladik. Pulmoner arterler yeni kesilmi5 kuzularin sol akciger alt loblarmdanizole edildi. ArterlerKrebs-Henseleitsolüsyonu
ile dolu olan izole organ banyosuna asildi ve izometrik kontraksiyonlar bilgisayarli poligrafi sistemi ile baglantili olan izometrik transdüsir
yoluyla devamli olarak kaydedildi. Solüsyon %75 N^- %20 0^- %5 COj (Normoksik) ve %95 N^- %5 COj (Hipoksik) kari^imi içeren gaziar ile
havalandinidi. Organ banyosundaki parsiyel oksijen konsantrasyonu oksijen elektrodu kullanilarak sürekli olarak ölcüldü. G¡ ve G^ proteinlerin
rolünü ara^tirmak için kolera ve pertusis toksini kullanildi. Çali^mada, dinlenme gerimindeki geni? çapli pulmoner arterlerde hipoksiye bagli
bir gerim artiji izlenmedi ancak hipoksi 3 ^ilVl 5-HT ile prekontrakte edilmi? dokularda kontraksiyona (1.7+0.5 mN/mm^ n=10) sebep oldu.
Hipoksik vazokonstriksiyon 2 |ig/ml kolera toksini ile inkübasyon sonrasi inhibe (2.6±0.4 mN/mm^'den 1.0±0.4 mN/mm^'ye kadar, n=6) ve
2 (ig/ml pertusis toksini ile inkübasyon sonrasi potansiyalize (0.6±0.4 mN/mm^'den 1.7±0.3 mN/mm^'ye kadar, n=6) oldu. Bu sonuçlar G¡ ve G,
proteinleri ile iliçkili sinyal iletiminin geni? çapli kuzu izole pulmoner arterinde gelljen hipoksik vazokonstriksiyonda önemli bir mekanizma
olabilecegini gösterdi.
Hypoxic pulmonary vasoconstriction (HPV) is an intrapulmonary adaptive mechanism that matches alveolar ventilation to perfusion. However during prolonged alveolar hypoxia HPV occurs with many pulmonary diseases. Despite intensive studies, cellular mechanisms of HPV are still not well defined. G proteins are a family of membrane-associated proteins believed to be involved in the transduction of various signals including the regulation of vascular tonus. In this study, we aimed to determine the contribution of G(i) and G(s) proteins in hypoxic vasoconstriction of lamb isolated pulmonary artery rings. Pulmonary arteries were isolated from left lower lobe of freshly slaughtered lamb. Arteries suspended in an organ bath filled with Krebs-Henseleit solution and isometric contraction recorded continuously via an isometric transducer connected to a computerised polygraphy system. The solution aerated with 75% N-2 - 20% O-2 - 5% CO2 (normoxic) and 95% N-2 - 5% CO2 (hypoxic) pO(2) of bathing medium was measured continuosly using an oxygen electrode. Pertussis toxin and cholera toxin were used to investigate the role of G(i) and G(s) proteins. In the present study, we observed that hypoxia had no effect on resting force in large artery rings, but it caused a further contraction (1.7 +/- 0.5 mN/mm(2), n=10) in 3 mu M 5-HT precontracted pulmonary arteries rings. Hypoxic vasoconstriction was inhibited by preincubation with 2 mu g/ml cholera toxins (from 2.6 +/- 0.4 mN/mm(2), to 1.0 +/- 0.4 mN/mm(2), n=6) and potentiated by preincubation with pertussis toxins (2 mu g/ml) (from 0.6 +/- 0.4 mN/mm(2), to 1.7 +/- 0.3 mN/mm(2), n=6). These results indicate that signal transduction mediated by G(i) and G(s) proteins may be an important mechanism in the hypoxic vasoconstriction in lamb isolated large pulmonary arteries.
Hypoxic pulmonary vasoconstriction (HPV) is an intrapulmonary adaptive mechanism that matches alveolar ventilation to perfusion. However during prolonged alveolar hypoxia HPV occurs with many pulmonary diseases. Despite intensive studies, cellular mechanisms of HPV are still not well defined. G proteins are a family of membrane-associated proteins believed to be involved in the transduction of various signals including the regulation of vascular tonus. In this study, we aimed to determine the contribution of G(i) and G(s) proteins in hypoxic vasoconstriction of lamb isolated pulmonary artery rings. Pulmonary arteries were isolated from left lower lobe of freshly slaughtered lamb. Arteries suspended in an organ bath filled with Krebs-Henseleit solution and isometric contraction recorded continuously via an isometric transducer connected to a computerised polygraphy system. The solution aerated with 75% N-2 - 20% O-2 - 5% CO2 (normoxic) and 95% N-2 - 5% CO2 (hypoxic) pO(2) of bathing medium was measured continuosly using an oxygen electrode. Pertussis toxin and cholera toxin were used to investigate the role of G(i) and G(s) proteins. In the present study, we observed that hypoxia had no effect on resting force in large artery rings, but it caused a further contraction (1.7 +/- 0.5 mN/mm(2), n=10) in 3 mu M 5-HT precontracted pulmonary arteries rings. Hypoxic vasoconstriction was inhibited by preincubation with 2 mu g/ml cholera toxins (from 2.6 +/- 0.4 mN/mm(2), to 1.0 +/- 0.4 mN/mm(2), n=6) and potentiated by preincubation with pertussis toxins (2 mu g/ml) (from 0.6 +/- 0.4 mN/mm(2), to 1.7 +/- 0.3 mN/mm(2), n=6). These results indicate that signal transduction mediated by G(i) and G(s) proteins may be an important mechanism in the hypoxic vasoconstriction in lamb isolated large pulmonary arteries.
Açıklama
Silan, Coskun/0000-0002-8352-6571; silan, coskun/0000-0002-8352-6571
WOS: 000333080000018
WOS: 000333080000018
Anahtar Kelimeler
Hypoxia, Pulmonary vasoconstriction, Cholera toxins, Pertussis toxins G-proteins, Lamb
Kaynak
Kafkas Universitesi Veteriner Fakultesi Dergisi
WoS Q Değeri
Q4
Scopus Q Değeri
Cilt
20
Sayı
2