Endothelin and renin - the angiotensin system and its relation to hypertension and hypertension organ damage

Renin-angiotensin and endothelin system play important role in blood pressure regulation. ln order to determine the contribution of an interaction between ET-I and ANG II to the development of hypertension and related end-organ damage in an ANG lI-dependent model of hypertension, we utilized a rat strain transgenic for the mouse Ren-2 renin gene (TGR; strain name TGR(mRen2)27). All our experimental studies have confirmed the crucial effect of increased natrium intake in a diet on development of arterial hypertension and hypertensive end- organ damage (especially kidneys and heart) in this model of arterial hypertension. Previous studies have demonstrated the presence of several types of endothelin system receptors - ETA and ET6 receptors with two subtypes- ETBl and ET62. Our study has brought a new knowledge of physiologic and pathophysiologic function of these receptors. The non- selective blockade of ETA and ETB receptors by Bosentan, improves survival rate of both homozygous and heterozygous transgenic animals, declines extent of hypertensive cardiac end-organ damage and reduce proteinuria and glomeru losclerosis. However, this positive effect of nonselective endothelin blockade is not caused due to decrease of arterial blood pressure. The reason for this fact is probably in various effects of..