IJCS | Volume 33, Nº4, July and August 2020

326 changes in the cyclic nucleotide balance, with a direct relationship with many diseases, including hypertension. 27 The availability of cAMP is also linked to hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, where beta-adrenergic stimulation activates adenylate cyclase, resulting in an increase in cAMP synthesis. 28 Increased cAMP raises the membrane potential, leading to higher depolarization rate, and subsequent increase in heart rate, acting as a second messenger in the modulation of HCN channels. 29 This could be a possible explanation for the cardiac abnormalities found in WKY. However, studies in the literature that explain these effects are scarce and technical limitations avoid us to validate this hypothesis, so further studies are needed to confirm it. El-Mosallamy et al., 30 demonstrated that L-NAME rats exhibited increase in RR interval, longer duration of the P wave and ST-segment elevation. However, in our results, the treatment with L-NAME induced an increase in QT, QTc and JT intervals at 15 weeks. Prolongation of QT and JT intervals are considered an indication of ventricular arrhythmia, the major cause of sudden death in hypertension. 12,31 The RR interval may change with dysregulation of the atrial electrical activity, and ceases to be constant in irregular heartbeats. 32 SHR showed increased RR interval, resulting in bradycardia. This change may be related to the ventricular extrasystole observed in this strain. 33 The PR interval corresponds to the period that electrical signals are delayed at the atrioventricular (AV) node, before it travels through the ventricular branches to induce cardiac depolarization and may be prolonged during AV nodal dysfunction. 34 Therefore, increased PR interval is also linked to bradycardia. 32 We found a failure in atrial conduction in SHR rats, which are consistent with the studies by Hazari et al., 35,36 that showed prolongation of PR interval in SHR compared with WKY. In addition to the atrial conduction delay, SHR also showed impaired ventricular conduction, with a decrease in QT and QTc, and shortening of QT at six weeks of life. These results are commonly related to electrolyte disorders such as hyperkalemia. 37 Hazari et al., 35 described that 12-week-old SHR have prolongation of the interval QT, JT and QTc. In our study, six-week-old SHR exhibited shorter duration of QT, JT and QTc intervals, which was probably related to hyperkalemia. 38-40 The ECG confirmed that SHR, beyond the electrical conduction failure, show T-wave inversion, which may lead to ischemic heart failure with advanced hypertension. Animal restraining, restraint- stress and difficulties with placing the electrodes in the same position in different rats are significant limitations of the method. Conclusion The present study shows that cardiac function is different in SHR compared with L-NAME rats. While SHR showed cardiac dysfunction, L-NAME exhibited changes in ventricular performance. Although decreased levels of PDE3A may have contributed to the changes observed in WKY, it was not sufficient to cause hypertension in this strain. Thus, all the hypertension models used in this study featured an increase in blood pressure, but each with its distinct adaptive mechanism. These results can serve as a basis for future studies on different types and models of hypertension. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding This study was funded by CAPES, Faepex-PRP, SAE‑Unicamp and FAPESP. Study Association This article is part of the thesis master submitted by Ana Gabriela Conceição-Vertamatti, from Universidade de Campinas . Ethics approval and consent to participate This study was approved by the Committee for Ethics in Animal Experimentation (CEUA) under the protocol number 2615-1. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study. Author contributions Conception and design of the research: Grassi-Kassisse DM. Acquisition of data: Conceição-Vertamatti AG, Borghi F, Ishizu LY, Costa GT, Ramos LA, Areas MA. Analysis and interpretation of the data: Conceição- Grassi-Kassisse et al. ECG in hypertension models Int J Cardiovasc Sci. 2020; 33(4):321-328 Original Article