No Expression of Angiotensin II Receptors and Angiotensin‐Converting Enzyme in Myxomatous Canine Mitral Valve Leaflets. An Autoradiographic Study

Abstract

The renin-angiotensin system, including angiotensin (Ang) II and angiotensin-converting enzyme (ACE), plays an important role in cardiac fibrous tissue formation. Since changes in valvular collagen are a central part of myxomatous mitral valve disease in the dog, we speculated that Ang II and ACE might play a role in the pathogenesis of this disease.In 10 mitral valves, five with and five without clear myxomatous changes, the presence and distribution of Ang II receptors and ACE was examined autoradiographically, using 125 I-Ang II and 125 I-lisinopril, respectively. At postmortem examination, diseased valves were taken from old dogs, control valves from young adult dogs.No significant level of Ang II and lisinopril binding was found in normal as well as diseased valve leaflets. Equally low, insignificant levels of 125 I-Ang II binding were found in the myocardium of dogs with and without valvular disease. No significant level of myocardial 125 I-lisinopril binding was found.The lack of autoradiographic evidence of Ang II receptors and ACE in normal and diseased canine mitral valve leaflets suggests that the renin-angiotensin system does not play a major role in the pathogenesis of the valvular changes.

Efficacy of Enalapril for Prevention of Congestive Heart Failure in Dogs with Myxomatous Valve Disease and Asymptomatic Mitral Regurgitation

“…Recent autoradiographic studies indicate that in canine atrioventricular valves as opposed to rat valves, angiotensin II receptors and ACE are scant. 25 This finding is at odds with the theory that local RAASs in the valves contribute to progressive valvular degeneration. In contrast, the canine myocardium has a comparably high concentration of angiotensin II receptors and ACE.…”

Signaling pathways in mitral valve degeneration

“…85 The same group reported no difference in Ang II and ACE binding between normal and degenerative canine mitral valves. 86 Ang II has been shown to directly increase expression of TGFb1 in human isolated cardiac fibroblasts. 87 ACE inhibition was found to inhibit TGFb3 synthesis in cultured canine mitral VIC.…”

An update on treatment and prognostic indicators in canine myxomatous mitral valve disease

“…Suggested reasons for the non–significant findings in the clinical trials include lack of activation of circulating RAAS activity in asymptomatic MMVD dogs (Häggström and others 1997), low concentration of angiotensin II receptors in the canine mitral valve (Mow and Pedersen 1999) or poor effect of ACE inhibitors on myocardial remodelling and progressive ventricular remodelling in MR (Häggström and others 1996a, Dell'Italia and others 1997). Indeed, more recent research has shown that myocardial remodelling caused by MR is a very complex process, which does involve angiotensin II, but is very difficult to counteract even if ACE and/or angiotensin II receptors are blocked (Perry and others 2002).…”