Abstract
For years, guanylate cyclase seemed to be homogenic and tissue nonspecific enzyme; however, in the last few years, in light of preclinical and clinical trials, it became an interesting target for pharmacological intervention. There are several possible options leading to an increase in cyclic guanosine monophosphate concentrations. The first one is related to the uses of analogues of natriuretic peptides. The second is related to increasing levels of natriuretic peptides by the inhibition of degradation. The third leads to an increase in cyclic guanosine monophosphate concentration by the inhibition of its degradation by the inhibition of phosphodiesterase type 5. The last option involves increasing the concentration of cyclic guanosine monophosphate by the additional direct activation of soluble guanylate cyclase. Treatment based on the modulation of guanylate cyclase function is one of the most promising technologies in pharmacology. Pharmacological intervention is stable, effective and safe. Especially interesting is the role of stimulators and activators of soluble guanylate cyclase, which are able to increase the enzymatic activity to generate cyclic guanosine monophosphate independently of nitric oxide. Moreover, most of these agents are effective in chronic treatment in heart failure patients and pulmonary hypertension, and have potential to be a first line option.
Highlights
Received: 22 April 2021Accepted: 2 June 2021Published: 4 June 2021Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Since the beginning of the 21st century, the treatment of metabolic disturbancesrelated diseases of the cardiovascular system has become deeper
The results presented by Friebe et al confirmed the crucial role of soluble guanylate cyclase (sGC) as a receptor for nitric oxide cyclase (NO)
Direct pharmacological intervention is the simplest way to modify receptor or enzyme answers. sGCs can be activated by NO or NO donors such as sodium nitroprusside; modulation of vascular smooth muscle reactivity was used in different clinical settings such as arterial hypertension and pulmonary arterial hypertension (PAH) to achieve rapid blood pressure stabilization in heart failure patients
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Since the beginning of the 21st century, the treatment of metabolic disturbancesrelated diseases of the cardiovascular system has become deeper. The target of treatment was rather clinical, whereas the clinical answer is important but the tools have changed; they are generally metabolic. GCs had seemed to be an homogenic and tissue nonspecific enzyme, whereas within the last few years, in light of preclinical and clinical trials, it became an interesting an target for pharmacological intervention. This review will focus on the role of direct and indirect modulation of guanylate cyclases in cardiovascular pharmacology
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