Molecular-specific effects of angiotensin II antagonists: clinical relevance to treating hypertension?
Angiotensin II receptor blockers (ARBs) may produce a number of molecule-specific effects that appear to be independent of interaction with the angiotensin II type 1 (AT1)-receptor. These include antagonism of the thromboxane A2 receptor, inhibition of platelet aggregation, induction of peroxisome proliferator- activated receptor gamma (PPARgamma) activity, and reduction of serum uric acid levels. However, definitive evidence is lacking that these molecule-specific effects give rise to a therapeutic advantage of one ARB over another. Currently, the possibility of a link between a molecule-specific effect of an ARB and an improvement in clinical outcomes is best illustrated by a reduction in serum uric acid levels with losartan. Data from Losartan Intervention For Endpoint reduction in hypertension (LIFE) study suggest a treatment-induced decrease in serum uric acid may contribute to the treatment benefit of a losartan-based versus atenolol-based therapy on the composite endpoint (death, myocardial infarction, or stroke). This finding should prompt further studies to investigate the long-term cardioprotective benefits issue of reducing hyperuricaemia in hypertensive patients.
Reid
John L
JL
Division of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, Scotland. j.l.reid@clinmed.gla.ac.uk
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism*; D047495:PPAR gamma / Q000096:biosynthesis*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors*; D014527:Uric Acid / Q000097:blood*
D047228:Angiotensin II Type 1 Receptor Blockers; D047495:PPAR gamma; D010975:Platelet Aggregation Inhibitors; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D014527:Uric Acid