Cardiomyopathy development protection after myocardial infarction in rats: Successful competition for major dihydropyridines’ common metabolite against captopril

Abstract

During the last 25 years angiotensin-converting enzyme inhibitors spectacularly conquered the field of cardiovascular diseases therapy. Nevertheless, lack of new studies concerning side effects associated with their chronic administration seems to be rather confusing. In our previous research, we proved that the main furnidipines’ metabolite (M-2) possess multiple cardioprotective actions. Currently, we compared effects of post-infarction long-term oral treatment with M-2 and captopril on hemodynamic parameters and “ischemic cardiomyopathy” development in rats. Myocardial infarction was evoked by permanent left anterior descending coronary artery occlusion for 35 days. Surviving rats were treated with captopril (2 × 25 mg/kg) or M-2 (4 mg/kg) from 6th– 35th day. At 35th day rats’ hearts were tested on working heart setup, where following parameters were measured: heart rate, preload pressure, aortic systolic and diastolic pressures, aortic maximum rise and fall, aortic and coronary flow, myocardial oxygen consumption and oximetry in perfusate. Subsequently, heart tissue specimens were assessed during morphological estimation. Captopril caused significant heart rate increase and markedly diminished preload pressure in comparison to M-2. Both drugs evoked essential aortic pressure increase. Aortic flow was significantly decreased after M-2, whereas captopril increased this parameter in comparison to M-2. Both agents caused marked coronary flow increase. Morphologic examination in captopril revealed cardiomyopathic process in 70% of hearts, whereas in M-2 this value reached 30%. Neovascularization of post-infarcted myocardium was visible only after M-2 therapy. Concluding, M-2 presented itself as more attractive agent in long-term post-infarction treatment by preventing cardiomyopathy development, angiogenesis stimulation and preserving cardiac performance.

Pirfenidone alleviates cardiac fibrosis induced by pressure overload via inhibiting TGF‐β1/Smad3 signalling pathway

“…CAP was implied to attenuate cardiac apoptosis and hypertrophy induced by TAC, which could be attributed to the inhibition of the Wnt3a/β‐catenin and the JAK2/STAT3 signalling pathway, respectively 7 . The anti‐hypertrophy role of CAP was validated in our study, however, side effects like coughing, nephrotoxicity and marked hemodynamic impact were inevitable when applying CAP to treating hypertension 27–29 . The present study showed the anti‐fibrotic effect of PFD was not inferior to CAP, which implied great potential in preventing cardiac remodelling and heart failure induced by hypertension without modulating blood pressure.…”

“…7 The anti-hypertrophy role of CAP was validated in our study, however, side effects like coughing, nephrotoxicity and marked hemodynamic impact were inevitable when applying CAP to treating hypertension. [27][28][29] The present study showed the anti-fibrotic effect of PFD was not inferior to CAP, which implied great potential in preventing cardiac remodelling and heart failure induced by hypertension without modulating blood pressure. In addition, our study provided a solid foundation for future clinical studies developing novel anti-fibrotic agents in hypertension.…”