Several recent clinical trials show that blocking agents of the renin-angiotensin-aldosterone system (RAAS) reduce cardiovascular events in patients with
metabolic syndrome based on
insulin resistance and
obesity, especially accumulated visceral fat. Our laboratory has focused on the relationship between the vascular RAAS and the action of
insulin on the vasculature. We first revealed that the addition of
insulin to cultured vascular smooth muscle cells (VSMC) markedly increases
angiotensinogen and
angiotensin II (Ang II) expression and production.
Insulin addition also induces VSMC growth that is inhibited by the blockade of the RAAS by either ACEI or ARB which suggests a role for the RAAS in
insulin-mediated growth.
Insulin has a quite different effect on cultured vascular endothelial cells (EC) as it reduces
angiotensinogen and
renin expression. However,
insulin added to EC induces a marked activation of ACE and the activated ACE promotes the conversion of Ang I to Ang II and cell growth under conditions of high
insulin concentration. Ang II induces the progression of
atherosclerosis through the production of oxidative stress that blocks
insulin signaling and accelerates
atherosclerosis. In this paper, we attempt to clarify the relationship between
insulin resistance, the RAAS, and oxidative stress in vascular tissues to mimic in vivo conditions found in patients with
metabolic syndrome and
obesity-related
hypertension as previously I reviewed in "Current
Hypertension Reviews" in 2010 [1]. In addition, I update the relationships between vascular RAAS and
insulin resistance for the last 4 years. JSH-2014 [2] states that the target goals of blood pressure (BP) for diabetes patients is lower than 130/80 mmHg, whereas updated JNC 8 [3] and ESH-ESC 2013 [4] recommends the target BP was changed to <140/90 mmHg for hypertensive patients with diabetes. Patients with diabetes and
hypertension have reduced mortality as well as improved cardiovascular and cerebrovascular outcomes with treatment to a goal SBP <150 mm Hg, but no randomized controlled trials support a goal <140/90 mm Hg. Despite this, the panel opted for a conservative recommendation in patients with diabetes and
hypertension, opting for a goal level of <140/90 mm Hg in adult patients with diabetes and
hypertension rather than the evidence based goal of <150/90 mm Hg [3, 5]. JSH-2014 recommends that the first choice of
antihypertensive medication should be RAAS blockers such as
ACE inhibitor or ARB. For the last several years, several large cohort clinical studies using ACEI and ARB have shown more favorable effects, but
aldosterone receptor inhibitor (
mineral corticoid receptor inhibitors; MR inhibitors) and
Renin Inhibitors have been withdrawn. Some studies showed the strong support to use these medications for diabetic patients. This review will discuss the relationships between vascular RAAS and
insulin resistance in patients with
hypertension and diabetes as previously reviewed with new updated findings for the last 4 years, and clinical implications based on updated JNC-8, ESH-ESC2013 and JSH-2014.