Bülent GÜMÜŞEL, Cengiz BOLCAL, Suat DOĞANCI, Elvin AKDAĞ, Howard LIPPTON, Ufuk DEMİRKILIÇ, Mehmet ARSLAN, Ertuğrul ÖZAL, Vedat YILDIRIM

Intermedin (IMD/AM2) dilates the pig coronary vascular bed through release of nitric oxide

Amaç: Bu çalışmada kalsitonin benzeri kalsitonin reseptörlerinin endojen bir agonisti olan intermedin/ adrenomedüllin-2'nin (IMD/AM2) koroner ve sistemik hemodinami üzerindeki etkileri araştırıldı. Çalışma planı: Aneztezi altındaki göğsü açık domuzların (n=6) sol ön inen koroner arterleri (LAD) etrafına ultrasonik geçiş süresi akım probları yerleştirildi. Proksimal LAD içerisine bir kateter yerleştirildi. İntrakoroner bolüs IMD, adrenomedüllin (hADM13-52) ve kalsitonin geniyle ilişkili peptid (CGRP) (1, 3, 10 μg) enjeksiyonları uygulandı ve koroner akım hızlarında meydana gelen değişiklikler sürekli olarak kayıt edildi.Bulgular: İntrakoroner bolüs IMD, hADM13-52 ve CGRP enjeksiyonları koroner kan akımlarını doza bağımlı şekilde artırdı. Araştırılan dozlarda IMD, CGRP ve hADM13-52'den daha güçlü bir etkiye sahip idi ve sistemik arteriyel basınçta, kalp debisinde ve kardiyak indekste değişikliğe neden olmadı. İntrakoroner NG-Nitro-L-argininemethyl ester (L-NAME) enjeksiyonu IMD'ye gelişen koroner vazodilatör yanıtı (CVR) anlamlı derecede azalttı.Sonuç: Bu çalışmanın verileri IMD'nin domuz koroner vasküler yatağı üzerine belirgin bir vazodilatör etkiye sahip olduğuna işaret etmektedir. Ayrıca bu veriler IMD'nin koroner vasküler yatakta endoteliyal nitrik oksit salımı ile ilişkili bir reseptör üzerinde etki gösterdiğine işaret etmektedir. IMD'ye gelişen CVR'nin derecesi koroner dolaşımdaki direnç bölümlerinde bulunan endoteliyal hücrelerin bütünlüğünün işlevsel bir göstergesi olarak kullanılabilir.

İntermedin (IMD/AM2), nitrik oksit salımı yoluyla domuz koroner vasküler yatağında dilatasyon sağlamaktadır

Background: This study investigated the effects of intermedin/ adrenomedullin-2 (IMD/AM2), an endogenous agonist for calcitonin-like calcitonin receptors, on coronary and systemic hemodynamics. Methods: Ultrasonic transit time flow probes were placed around the left anterior descending (LAD) artery in the anesthetized, open-chest pig (n=6). A catheter was placed into the proximal LAD. Intracoronary arterial bolus injections of IMD, adrenomedullin (hADM13-52) and calcitonin gene related peptide (CGRP) (1, 3, 10 μg) were performed and the changes in the velocity of coronary blood flows were continuously recorded.Results: Intracoronary artery bolus injections of IMD, hADM13-52 and CGRP increased coronary blood flow in a dose-dependent manner. At the studied doses, IMD was more potent than CGRP and hADM13-52 and did not alter systemic arterial pressure, cardiac output and cardiac index. Intracoronary artery injection of NG-Nitro-Larginine- methyl ester (L-NAME) significantly decreased the coronary vasodilator response (CVR) to IMD.Conclusion: The present data suggest that IMD possesses marked vasodilator activity in the pig coronary vascular bed. The present data further suggest that IMD acts on a receptor in the coronary vascular bed that is coupled to endothelial nitric oxide release. The degree of the CVR to IMD may serve as functional marker for the integrity of endothelial cells in resistance segments of the coronary circulation

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