Vascular hypertrophy in hypertension: role of the renin-angiotensin system.
Angiotensin II is vasoconstrictor and antinatriuretic; it also stimulates cell growth and proliferation in vascular smooth muscle, resulting in hypertrophy or hyperplasia of conduit and resistance vessels. These actions are mediated through angiotensin II receptors (AT1 subtype), which activate several G-protein-dependent intracellular transduction pathways, such as the phospholipase C, diacylglycerol and inositol trisphosphate the mitogen-activated protein (MAP) kinase pathway, and Janus kinase (JAK)-signal transducers and activators of the transcription (STAT)-mediated pathway. These can all increase the expression of certain proto-oncogenes, particularly c-fos. Angiotensin II also stimulates the activity of certain growth factors, such as platelet-derived growth factor-A-chain and basic fibroblast growth factor. The cellular responses to angiotensin II in vascular smooth muscle have been shown in different hypertensive vessels to be either hypertrophy alone, hypertrophy and DNA synthesis without cell division (polyploidy), or DNA synthesis with cell division (hyperplasia). In genetic hypertension, there is either cellular hyperplasia or remodeling, whereas in renovascular hypertension, there is hypertrophy of vascular smooth muscle cells. Angiotensin-converting enzyme (ACE) inhibitors prevent or reverse vascular hypertrophy in animal models of hypertension. In human hypertension, ACE inhibitors reduce the increased media/lumen ratio of large and small arteries and increase arterial compliance. These properties are also shared by AT1 receptor antagonists. The implications of these findings for morbidity and mortality in hypertension still await rigorous testing in prospective clinical trials.
Rosendorff
C
C
Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
D000804:Angiotensin II / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology*; D002455:Cell Division; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D006984:Hypertrophy; D011945:Receptors, Angiotensin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D000804:Angiotensin II