Dissociation of blood pressure reduction from end-organ damage in TGR(mREN2)27 transgenic hypertensive rats

Objective Since the biochemical disturbance underlying hypertension may be an important determinant of patient outcome, we compared the effects of ear ly treatment with different antihypertensive drugs on end-organ damage in t he TGR(mREN2)27 transgenic rat (REN-P), In these REN-P rats, hypertension i s primarily caused by increased activity of the tissue renin-angiotensin sy stem. Design and methods Seven-week-old REN-5 rats were either untreated or treat ed orally with an optimal daily dose of carvedilol (30 mg/kg), hydralazine (30 mg/kg), losartan (10 mg/kg) or quinapril (15 mg/kg), Nontransgenic litt ermates served as normotensive controls. After 11 weeks of treatment, we de termined plasma norepinephrine concentrations, left ventricular atrial natr iuretic factor messenger RNA and cardiac and vascular function and hypertro phy. Results Chronic treatment with carvedilol and hydralazine significantly dec reased blood pressure to a similar lever but failed to normalize it, wherea s both losartan and quinapril completely normalized blood pressure. Despite a blood pressure reduction in ail treatment groups, only losartan, quinapr il and hydralazine preserved endothelial function, while carvedilol did not Furthermore, losartan and quinapril prevented cardiac and medial hypertrop hy. The expression of atrial natriuretic factor messenger RNA paralleled th e hemodynamic changes. Plasma norepinephrine levels were normalized by losa rtan or quinapril but remained increased after carvedilol and hydralazine t reatment Conclusions In REN-5 hypertensive rats, end-organ damage can be prevented b y both inhibition of the angiotensin converting enzyme and blockade of the angiotensin II type 1 receptor, but not by merely lowering blood pressure. When blood pressure is not fully normalized, the effects on end-organs are clearly dissociated from the antihypertensive effects. (C) Lippincott Willi ams & Wilkins.