Během vývoje musely živočišné druhy čelit měnícím se životním podmínkám. Na tyto změny bylo nutno se adaptovat. Tak například v době, kdy primitivní obojživelníci opouštěli mateřské prostředí a vydávali se z moře na souš, vznikly v souvislosti se změnou životního prostředí nové regulační systémy, které umožnily přežití na souši – zajistily udržení vnitřního prostředí a krevního tlaku v nových podmínkách...

In the course of evolution, animal species faced changes in the environment and had to adapt to them. For instance, during the period when primitive amphibians were leaving the original marine environment to become terrestrial, new regulatory systems developed in response to this challenge to allow survival in terrestrial conditions by maintaining the internal environment and blood pressure under new conditions. The renin-angiotensin-aldosterone system (RAAS) emerged as well as other mechanisms (e.g., kinine or apelin system) that control action of this system involved in vasoconstriction, sodium retention and inflammation activation. Unfortunately, in a range of pathologies such as hypertension, heart failure or diabetes, the system is unbalanced, i.e., shifted toward vasoconstriction, volume expansion and inflammatory reaction. RAAS in particular is upregulated and its hyperactivity considerably accelerates progression of cardiovascular disease. For this reason, the system needs to be controlled. As the diseases mentioned above affect at least 40 % of the European population, the drugs targeting RAAS, i.e., angiotensin converting enzyme (ACE) inhibitors, sartans, renin inhibitors or mineralocorticoid receptor inhibitors, have come to the forefront of attention. Other candidate therapies targeting RAAS or other associated systems are under clinical evaluation. Angiotensin 1-7 analogues, apelin system activators, Rho-kinase inhibitors and aldosterone synthase inhibitors can be given as examples. At present, after 50 years from the elucidation of the basic mechanisms of action of renin and angiotensin II, a review is presented of new knowledge on how to restore the impaired balance. Last but not least, the article provides information on upcoming activities in development laboratories of pharmaceutical companies.

Ústav farmakologie 3 LF UK Praha

Renin-angiotensin-aldosterone system - there are always new surprises half a century from the elucidation of its function

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