ABSTRACT
This study investigated whether sacubitril/valsartan and ivabradine are able to prevent left ventricular (LV) fibrotic remodelling and dysfunction in a rat experimental model of spontaneous hypertension (spontaneously hypertensive rats, SHRs) and whether this potential protection is associated with RAAS alterations. Five groups of three-month-old male Wistar rats and SHRs were treated for six weeks as follows: untreated Wistar controls, Wistar plus sacubitril/valsartan, SHR, SHR plus sacubitril/valsartan, and SHR plus ivabradine. The SHRs developed a systolic blood pressure (SBP) increase, LV hypertrophy and fibrosis, and LV systolic and diastolic dysfunction. However, no changes in serum RAAS were observed in SHRs compared with the controls. Elevated SBP in SHRs was decreased by sacubitril/valsartan but not by ivabradine, and only sacubitril/valsartan attenuated LV hypertrophy. Both sacubitril/valsartan and ivabradine reduced LV collagen content and attenuated LV systolic and diastolic dysfunction. Sacubitril/valsartan increased the serum levels of angiotensin (Ang) II, Ang III, Ang IV, Ang 1-5, Ang 1-7, and aldosterone, while ivabradine did not affect the RAAS. We conclude that the SHR is a normal-to-low serum RAAS model of experimental hypertension. While the protection of the hypertensive heart in SHRs by sacubitril/valsartan may be related to an Ang II blockade and the protective Ang 1-7, the benefits of ivabradine were not associated with RAAS modulation.
ABSTRACT
The heart releases natriuretic peptides (NPs) which represent an important hormonal axis with cardiorenal protective effects. In view of their properties, NPs have pathophysiologic, diagnostic and prognostic implications in several cardiovascular diseases (CVDs). Severe pulmonary inflammation, as induced by the SARS-COV2, may increase pulmonary pressure with potential influence on NPs release, whereby normal cardiovascular integrity becomes impaired. Moreover, pre-existing CVDs are strong negative prognostic factors since they exacerbate the effects of the viral infection and lead to worse outcomes. In this context, it may be expected that NPs exert a key protective role toward the virus infection whereas an impairment of NPs release contributes to the virus deleterious effects. In this review article we explore the potential involvement of NPs in the COVID-19 disease. To this aim, we will first focus on the interactions between NPs and the Ang II/ATIR arm of the renin-angiotensin-aldosterone system (RAAS) as well as with the protective ACE2/Ang (1-7) arm of the RAAS. Subsequently, we will review evidence that strongly supports the role of increased NT-proBNP level as a marker of cardiac damage and of worse prognosis in the COVID-19 affected patients. Finally, we will discuss the potential therapeutic benefits of these protective hormones toward the viral infection through their endothelial protective function, anti-inflammatory and anti-thrombotic effects. In conclusion, the potential implications of NPs in the SARS-CoV-2 infection, as discussed in our article, represent an important issue that deserves to be fully investigated.