Losartan improves resistance artery lesions and prevents CTGF and TGF-beta production in mild hypertensive patients.
Although structural and functional changes of resistance arteries have been proposed to participate in arterial hypertension (HTA) outcome, not all therapies may correct these alterations, even if they normalize the blood pressure (BP). The aim of this study was to investigate the mechanisms of the protection afforded by the angiotensin receptor antagonist losartan in resistance arteries from patients with essential HTA. In all, 22 untreated hypertensive patients were randomized to receive losartan or amlodipine for 1 year and the morphological characteristics of resistance vessels from subcutaneous biopsies were evaluated. Protein expression of connective tissue growth factor (CTGF), transforming growth factor beta (TGF-beta), and collagens III and IV was detected by immunohistochemistry. In comparison with normotensive subjects, resistance arteries from hypertensive patients showed a significant media:lumen (M/L) ratio increment and a higher protein expression of CTGF, TGF-beta, and collagens. After 1 year of treatment, both losartan and amlodipine similarly controlled BP. However, M/L only decreased in patients under losartan treatment, whereas in the amlodipine-treated group this ratio continued to increase significantly. The administration of losartan prevented significant increments in CTGF, TGF-beta, and collagens in resistance arteries. By contrast, amlodipine-treated patients showed a higher vascular CTGF, TGF-beta, and collagen IV staining than before treatment. Our results show that the administration of losartan, but not amlodipine, to hypertensive patients improves structural abnormalities and prevents the production of CTGF and TGF-beta in small arteries, despite similar BP lowering. These data may explain the molecular mechanisms of the better vascular protection afforded by drugs interfering with the renin-angiotensin system.
Vascular Biology and Atherosclerosis Research Laboratory, Medicina Interna III, Hospital Clínico San Carlos, Madrid, Spain.
D
D
Gómez-Garre
J L
JL
Martín-Ventura
R
R
Granados
T
T
Sancho
R
R
Torres
M
M
Ruano
J
J
García-Puig
J
J
Egido
D000328:Adult; D017311:Amlodipine / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001158:Arteries / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D055513:Connective Tissue Growth Factor; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D017874:Immediate-Early Proteins / Q000502:physiology*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D019808:Losartan / Q000627:therapeutic use*; D008875:Middle Aged; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D014655:Vascular Resistance / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D017311:Amlodipine; D019808:Losartan