The discovery that SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) binds to the angiotensin converting enzyme (ACE)-2, which is highly expressed in the lower airways, explained why SARS-CoV-2 causes acute respiratory distress syndrome (ARDS) and respiratory failure. After this, the news spread that ACEis and ARBs would be harmful in SARS-CoV-2-infected subjects.To the contrary compelling evidence exists that the ACE-1/angiotensin (Ang) II/ATR-1 pathway is involved in SARS-CoV-2-induced ARDS, while the ACE-2/Ang (1-7)/ATR2/MasR pathway counteracts the harmful actions of AngII in the lung. A reduced ACE-1/ACE-2 ratio is, in fact, a feature of ARDS that can be rescued by human recombinant ACE-2 and Ang (1-7) administration, thus preventing SARS-CoV-2-induced damages to the lung. Based on the current clinical evidence treatment with ACE-inhibitors I (ACEis) or angiotensin receptor blockers (ARBs) continues to provide cardiovascular and renal protection in patients diagnosed with COVID-19. Discontinuing these medications may therefore potentially be harmful in this patients population. COVID19 PandemicsThe pandemic proportions of Covid-19 (Coronavirus Disease 2019) from the SARS (Severe Acute Respiratory Syndrome) Coronavirus 2 (CoV-2) infecting a million and killing 47,266 people worldwide as of April 2, has fueled enormous interest in the mechanisms whereby this new coronavirus causes acute respiratory distress syndrome (ARDS) and multiorgan failure. The estimated 79% infection rate from undocumented cases in Covid-19 patients (Li et al., 2020), and the high lethality of the infections, along with its enormous socio-economic impact, emphasise the importance of fully understanding these mechanisms for developing effective treatment strategies.Early in 2020 reports of the full RNA sequence of the SARS-CoV-2 virus highlighted remarkable similarities with the SARS-CoV virus, which was responsible of an outbreak that killed 774 people in 2003(Xu et al., 2020. As the processes whereby the SARS-CoV virus infects the lung cells were already dissected (Kuba et al., 2005), and it was held that SARS-CoV-2 uses identical mechanisms, these discoveries allowed an unprecedented acceleration of knowledge.

1. The generation of superoxide anions (02-) by intact pig coronary artery rings was measured using a lucigenin-enhanced chemiluminescence technique and a histochemical technique with Nitroblue Tetrazolium (NBT) staining. 2. Isolated arteries with intact endothelium generated 02 at a rate of 9 0 + 0-8 pmol min' (mg dry weight)-1; this rate was diminished by about 24% when the endothelium was removed. The NBT staining of arterial ring preparations showed formazan precipitation mainly in the intima. Arterial rings were pretreated with diethylthiocarbamate in order to inhibit Cu-Zn superoxide dismutase (SOD) activity which increased the 2-generation by 184 + 55% (n = 10; P < 0-01). Stimulation of protein kinase C with phorbol 12-myristate 13-acetate (5 FM) enhanced endothelium-dependent 2-generation by 136 + 20% (n = 19; P< 0-01). Neither stimulation with bradykinin or substance P, nor inhibition with NG-nitro-L-arginine methyl ester of endothelial nitric oxide synthase had a significant effect on 02-generation. In contrast, the inhibition of flavoproteins with diphenyliodonium 4. The results suggest that intact coronary arteries do generate O2-under basal conditions and that the endothelial layer significantly contributes to this phenomenon. This generation of 02-is greatly influenced by intrinsic SOD activity. It is suggested that basal vascular 02-generation is mainly due to membrane-bound NAD(P)H oxidase activity and/or tetrahydrobiopterin-dependent processes.

No abstract

No abstract

No abstract