Angiotensin II-induced inotropism requires an endocardial endothelium-nitric oxide mechanism in the in-vitro heart of Anguilla anguilla

• Published in: Journal of Experimental Biology
• Main Authors: Imbrogno, Sandra, Cerra, Maria Carmela, Tota, Bruno
• Format: Text
• Language: English
• Published: Company of Biologists 2003
• Subjects: Research Article; Triton; Anguilla anguilla
• Online Access: http://jeb.biologists.org/cgi/content/short/206/15/2675; https://doi.org/10.1242/jeb.00468

Using an isolated working heart preparation we show that angiotensin II (ANG II), at concentrations of 10-10–10-7 mol l-1, elicits negative chronotropism and inotropism in the freshwater eel Anguilla anguilla . The negative inotropism was insensitive to losartan and CGP42112 (AT 1 and AT 2 ANG II receptor antagonists, respectively), and was abrogated by the AT 1 receptor antagonist CV11974, the G protein blocker pertussis toxin (PTx) and the muscarinic antagonist atropine. In contrast, it was not affected by the adrenoceptor antagonists propanolol, sotalol and phentolamine. Using donors (<scp>l</scp>-arginine) and inhibitors [NG-monomethyl- L -arginine (<scp>l</scp>-NMMA), <scp>l</scp>-N5(1-iminoethyl)ornithine ( L -NIO)] of nitric oxide synthase (NOS), and haemoglobin as NO scavenger, we demonstrate that NO signalling is involved in ANG II-mediated inotropism. Pretreatment with Triton X-100, a detergent that damages the endocardial endothelium (EE), or with 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ), a specific inhibitor of soluble guanylate cyclase, or with the cGMP-activated protein kinase (PKG) inhibitor KT5328, abolished ANG II-mediated inotropism. Thus, ANG II-mediated inotropism occurs via an EE-NO-cGMP-PKG mechanism. ANG II did not affect the mechanical performance influenced by preload changes (i.e. the Frank–Starling response), which in the eel heart is modulated by NO. This EE-paracrine-mediated cardio-suppressive action of endoluminal ANG II suggests that the hormone plays an important intracardiac role in the fish heart.