Changes of plasma endothelin and growth factor levels, and of left ventricular mass, after chronic AT1-receptor blockade in human hypertension.
The stimulation of autocrine and paracrine factors such as basic fibroblast- (bFGF) and platelet-derived (PDGF) growth factors mediates many of the growth-promoting actions of angiotensin II. The aim of this study was to evaluate the effect of chronic AT1-receptor blockade on plasma endothelin-1 (ET-1) and growth factors levels, and on left ventricular mass, in essential hypertension (EH). The study population consisted of 16 patients with mild-moderate EH, and 25 normotensive controls. In the EH patients under basal conditions, and after 3 and 6 months of chronic therapy with Losartan 50 mg/day, we measured serum levels of ET-1, bFGF and PDGF, and tumor necrosis factor (TNF). At the same time, all patients underwent 24-h ambulatory blood pressure monitoring and an echocardiographic evaluation to measure the thickness of the posterior wall (PWT) of the left ventricle and of the interventricular septum (IVS). The healthy controls underwent the same analyses, under basal conditions, at baseline and after 3 and 6 months of observation. In the EH patients, after 3 months of AT1-receptor blockade bFGF was reduced from 13.6 +/- 0.7 to 10.9 +/- 0.7 pg/mL (P < .004), and both TNF and PDGF were significantly decreased (P < .006 and P < .007, respectively). After 6 months of therapy, ET-1 was significantly diminished in comparison with baseline (6.9 +/- 0.8 v 5.5 +/- 0.1 fmol/mL; P < .05), and the reduction in the levels of growth factors were even more significant than at 3 months of treatment. Both PWT and IVS were significantly changed after 6 months of therapy with losartan after basal evaluation (P < .05, respectively). Systolic and diastolic 24-h blood pressures declined significantly after 3 and 6 months of therapy with losartan (P < .01, respectively). It seems likely that the inhibition of the action of angiotensin II by the specific AT1-receptor blockade, by reducing circulating levels of ET-1 and those of some growth factors, may offer an advantage regarding the effect on hypertensive cardiovascular changes in human hypertension.
Cottone
S
S
Istituto di Clinica Medica e Malattie Cardiovascolari, Cattedra di Medicina Interna, University of Palermo, Italy.
Vadalà
A
A
Vella
M C
MC
Nardi
E
E
Mulé
G
G
Contorno
A
A
Riccobene
R
R
Cerasola
G
G
D000328:Adult; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002908:Chronic Disease; D016232:Endothelins / Q000097:blood*; D005260:Female; D006133:Growth Substances / Q000097:blood*; D006352:Heart Ventricles; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D009206:Myocardium / Q000473:pathology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D016232:Endothelins; D006133:Growth Substances; D019808:Losartan