Insulin-mediated regulation of the endothelial renin???angiotensin system and vascular cell growth

Abstract

Either low or high levels of insulin suppressed angiotensinogen and renin expression, however, high doses of insulin stimulated ACE activity in cultured human aortic EC. This may indicate that insulin regulates vascular cell growth and endothelial function via bifunctional modification of the vascular angiotensin generation.

Treatments for Hypertension in Type 2 Diabetes-Non-Pharmacological and Pharmacological Measurements

“…Ang II mediated production of reactive oxygen species (ROS) promotes growth factors, cytokines and chemotactic factors relating to atherosclerosis [65]. A high level of insulin, as occurs in insulin resistance states, induces the activation of the tissue RAAS in blood vessels and the heart, and leads to an overproduction of Ang II in these tissues [33,58]. High levels of insulin directly activate the expression and production of angiotensin, cell growth through www.intechopen.com the angiotensin I receptor and the conversion of Ang I to Ang II in vascular smooth muscle cells.…”

“…High levels of insulin directly activate the expression and production of angiotensin, cell growth through www.intechopen.com the angiotensin I receptor and the conversion of Ang I to Ang II in vascular smooth muscle cells. Although the mechanisms leading to the initial activation of tissue Ang II in high-risk conditions such as type 2 diabetes and hypertension, RAAS blocking agents such as angiotensin converting enzyme inhibitors (ACE inhibitors) and Ang II receptor blockers (ARBs), inhibits the multi-factorial effects of Ang II and reduce the frequency of cardiovascular events as observed in the HOPE and LIFE studies [58,66,67]. The HOPE Study (the Heart Outcomes Prevention Evaluation study) showed that high plasma rennin activity is an independent predictor of major vascular events and mortality in a stable population of high-risk patients with atherosclerosis and/or diabetes [58].…”

“…Several strategies are available for RAAS blockade, including angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blocker (ARBs), renin inhibitors (Aliskiren) and mineralocorticoidreceptor blockers, which have been proven in the clinical studies to result in improvements in cardiovascular disease and chronic kidney disease outcomes. Likewise, while hypertension in obesity, metabolic syndrome or type 2 diabetes, benefits from therapeutic lifestyle change, recently, clinical and epidemiological studies have shown that ACE inhibitors and ARBs are highly efficacious, persistent and well-tolerated antihypertensive agents, due to their cardio-and renal-protective benefits [58,66,67] . Moreover they have further beneficial effects in preventing complications of obesity and diabetes, such as progression of diabetic nephropathy, metabolic syndrome.…”

“…diabetes, ischemic heart disease, heart failure, and proteinuria) is now well-established. The Heart Outcomes Prevention Evaluation (HOPE) study established that the significant effect of ACE inhibition (ramipril) on cardiovascular morbidity and mortality occurred through mechanisms beyond pure blood pressure control [58,66]. Additionally, a recent analysis from the Blood Pressure Lowering Treatment Trialist's Collaboration showed that ARBs-based and ACE inhibitors -based treatment regimens were comparable in terms of the odds ratio for stroke and heart failure, independent of blood pressure reduction [111].…”

“…Similarly, sympathetic activation and insulin resistance are strongly linked to the onset and development of hypertension [51,52] and diabetes [54]. Furthermore, stimulation of the renin-angiotensin-aldosterone system (RAAS) is frequently demonstrated in obesity and hypertension [55,56], and may be related to insulin resistance either via direct or indirect mechanisms [57,58].…”