Lokal Renin Anjiyotensin Sistemi: Fizyolojik ve Patofizyolojik Etkinliği

Abstract

Abstract Local Renin-Angiotensin System: Physiologic and Pathophysiologic Effects Renin-angiotensin system (RAS) is one of the most important physiological systems which determines and protects the blood pressure by its effects on fluid and electrolyte balance. Since the first identification of renin molecule by Tigerstedt and Bergmann in 1898, the renin-angiotensin system (RAS) has been extensively studied. Angiotensin II, the most dominant effector peptide of the RAS, regulates cellular growth in a wide variety of tissues in (patho)biological states. In addition to the circulating (endocrine) RAS, the existence of RAS in varies tissues and diverse cells has also known. Recent studies have provided evidence of a complete, local RAS within cells, described as an 'intracrine' or intracellular system. The prorenin/ (Pro)renin receptor (PRR)/MAP kinase axis, the ACE2/Ang (1-7)/Mas receptor axis, and the Ang IV/AT II/insulin-regulated aminopeptidase axis also have recently been discovered. From the concept of local RAS, the effect of RAS on tissue and organ levels regardless from its systemic activity is understood. The evidence for physiological and pathophysiological effects of local RAS activities such as cell growth, differantion, proliferation, apoptosis, and formation of reactive oxygen products, tissue inflammation and fibrogenesis is gradually accumulated. Local actors other than the renin (chymase, tonin, i.e.) are thought to be more important in the regulation of local RAS. On the other hand, the members of the circulating RAS contribute to the activity of local RAS in tissues with the exception of brain. A better understanding of the autocrine and paracrine mechanisms involved in the local RASs might direct future organ-specific therapy. With this review, it was aimed to attract more attention to local RAS concept and its effects because of the complexity of the system and more widely use of the drugs affecting it.

Keywords

• Renin-angiotensin system; angiotensin II; angiotensin-converting enzyme 2; receptor

Lokal Renin Anjiyotensin Sistemi: Fizyolojik ve Patofizyolojik Etkinliği

Abstract

Türkçe Özet: Renin anjiyotensin sistemi (RAS), sıvı ve elektrolit dengesine yaptığı etkilerle kan basıncını belirleyen ve koruyan en önemli fizyolojik sistemlerdendir. İlk kez 1898 yılında Tigerstedt ve Bergmann\'ın renin molekülünü bulmasından bu yana RAS oldukça geniş bir biçimde çalışılmıştır. Anjiyotensin II (ATII), RAS\'ın en fonksiyonel molekülüdür ve birçok biyolojik ve patobiyolojik süreçte etkin rol oynar. Sistemik dolaşımdaki RAS aktivitesinden başka farklı hücre ve dokularda RAS varlığı ve etkinliği de gösterilmiştir. Yakın zamanda yapılan çalışmalar ile, intrakrin ya da “hücre içi” RAS olarak da bilinen lokal RAS\'ın etkinliği gösterilmiştir. Prorenin/Prorenin reseptör/MAP kinaz aksı, anjiyotensin dönüştürücü enzim 2 ADE2/Anjiyotensin (1-7)/Mas reseptör aksı ve anjiyotensin IV/ATII/insulin-regulated aminopeptidaz gibi süreçler yakın zamanda tanımlanmıştır. Lokal RAS varlığının, bulunduğu doku ya da organda; hücre büyümesi, farklılaşması, çoğalması, apoptozisi, reaktif oksijen ürünlerinin oluşumu, doku inflamasyonu ve fibrogenezdeki fizyolojik ve patofizyolojik rollerine dair kanıtlar giderek artmaktadır. Lokal RAS\'ta renin dışındaki faktörlerin (kimaz, tonin vb.) bu sistemin düzenlenmesinde daha baskın olduğu düşünülmektedir. Öte yandan, dolaşımdaki RAS üyeleri de, beyin dışındaki dokularda lokal RAS aktivitesine katkıda bulunmaktadır. Otokrin ve parakrin mekanizmaların daha iyi anlaşılmasıyla organ spesifik tedavide yeni ufukların açılması muhtemeldir. Bu derleme ile sistemin karmaşıklaşmasına ve bu sistemi etkileyen ilaçların yaygın kullanımı nedeniyle lokal RAS kavramı ve etkinliğine dikkat çekilmesi amaçlanmıştır.

Keywords

• Renin-anjiotensin sistemi; anjiotensin II; anjiotensin dönüştürücü enzim 2; reseptör

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