Partial peroxisome proliferator-activated receptor agonist angiotensin receptor blockers. Potential multipronged strategy in stroke prevention.
OBJECTIVE
Although their primary mechanism of action is blood pressure lowering, emerging data suggest that select angiotensin receptor blockers (ARBs), which partially activate the peroxisome proliferator-activated receptor gamma (PPAR-gamma), may effectively treat insulin resistance and dyslipidemia without the toxicity sometimes associated with full PPAR-gamma agonists. Since up to 50% of the patients with ischemic stroke and transient ischemic attack harbor insulin resistance, drugs that simultaneously control hypertension and insulin resistance could be particularly useful for stroke prevention.


RESULTS
This review presents the experimental and preliminary clinical evidence supporting a promising role for partial PPAR-gamma agonist ARBs in treating insulin resistance and the metabolic syndrome in patients with ischemic cerebrovascular disease.


CONCLUSIONS
Partial PPAR-gamma agonist ARBs by virtue of their multiple beneficial mechanisms of action could provide a single multipronged strategy for reducing future vascular events in persons with, or at risk for, stroke.
Towfighi
Amytis
A
Division of Stroke and Critical Care, Department of Neurology, University of Southern California, Los Angeles, CA 90033, USA. towfighi@usc.edu
Ovbiagele
Bruce
B
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D054333:Drug Partial Agonism; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy; D009765:Obesity / Q000150:complications / Q000188:drug therapy; D047495:PPAR gamma / Q000819:agonists*; D012084:Renin-Angiotensin System / Q000187:drug effects; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D047495:PPAR gamma