Multi‐therapeutic action of chronic treatment with tadalafil in cardiovascular alterations and erectile function of rats with heart failure
Authors: Claudino Mario Angelo , Tartarotti Sabrina Payne , Mora Aline Gonçalves , Janussi Sabrina , Krikorian Karla , Andrade Douglas , Priviero Fernanda 
Published: June 2021

IntroductionHeart failure (HF) is the common endpoint of several cardiovascular diseases. HF and ED share similar pathophysiological mechanisms that contribute to the progression of both disorders, with emphasis on endothelial dysfunction and reduced nitric oxide (NO) bioavailability. Drugs mimic the effect exerted by NO, such as tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor used in the ED treatment. Therefore, tadalafil may be a multi‐therapeutic agent in the treatment of cardiovascular alterations and erectile dysfunction associated with impaired of NO‐sGC‐cGMP signaling pathway? Thus, using the aortocaval fistula model (FAC) we investigated the contribution of tadalafil chronic treatment in the cardiac, vascular and erectile dysfunction of HF rats.MethodsHF was surgically induced through the FAC model, and after 8 weeks, these animals were submitted to cardiac function evaluation (echocardiogram) and subdivided into 3 groups: Sham, HF and HF/Tadalafil (5mg/day IP for more 4 weeks). Intracavernous pressure measurement (ICP) was used to evaluate erectile function in vivo. Response concentration curves were constructed to assess both vascular reactivity in response to phenylephrine (PE), acetylcholine and sodium nitroprusside (SNP), as well as the cavernosal muscle (CC) reactivity in response to PE and SNP. Electrical stimulation (EFS) were obtained to evaluate neurogenic contraction and nitrergic relaxation in CC rat.ResultsAfter 12 weeks, HF group presented both reduced of ejection and shortening fraction (p<0.05), as well present cardiac hypertrophy (P <0.05) when compared to the Sham group. Treatment with tadaladil restored the ejection and shortening fraction in the HF/Tadalafil (p<0.05), and reduced cardiac hypertrophy induced by HF. Moreover, HF animals presented an increase in the contractile vascular response mediated by PE when compared to Sham group (p<0.05), being this vascular hypercontractility restored by the tadalafil treatment (p<0.05). In addition, aorta of HF rats showed reduction of the ACh‐mediated relaxation (p<0.05) compared to the control, and this effect was restored by tadalafil treatment (p<0.05). Regarding erectile function, the data show that HF animals present a reduction of intracavernous pressure (p<0.05) compared to the Sham group, that was restored by tadalafil treatment (p<0.05). The contractile mechanism of CC, in response to PE and neurogenic electrical stimulation (p<0.05) were increased in HF rats, on the other side, the treatment with tadalafil improve the CC hypercontractility in these animals (p<0.05). In addition, tadalafil treatment also restored both SNP (p<0.05) and nitrergic (p<0.05) mediated relaxation in the CC of HF rats.ConclusionOur data show that the chronic treatment with tadalafil improved both vascular‐ and no‐vascular smooth muscle reactivity since exerting beneficial effects in the cardiovascular and erectile function in HF rats. Data suggesting that tadalafil acts is a multi‐therapeutic agent in HF rats.Support or Funding InformationFinancial suport: FAPESP: 2011/21095‐4 / CNPq: 423987/2016‐0This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.