Fig. 4.

Proposed mechanistic hypothesis based on the published data and the results of the present study in patients with ADPKD. A vicious cycle is created, in which renal cysts activate the renin-angiotensin-aldosterone system (RAAS). The resulting increase in ANG II leads to 1) increased levels of endothelial nitric oxide synthase (NOS) inhibitor ADMA and SDMA that deplete nitric oxide (NO); 2) increased Hcy and SAH levels within the methylation pathway and lower SAM/SAH ratio, indicating diminished methylation capacity; and 3) increased metabolism of arachidonic acid (AA), leading to generation of proinflammatory and oxidative stress, accelerating prostaglandins. Oxidative stress, vascular inflammation, and endothelial dysfunction in turn augment the cyst compression of renal vasculature and activate RAAS.