Effect of treatment with candesartan or enalapril on subcutaneous small artery structure in hypertensive patients with noninsulin-dependent diabetes mellitus.
Structural alterations of subcutaneous small resistance arteries are associated with a worse clinical prognosis in hypertension and noninsulin-dependent diabetes mellitus (NIDDM). However, no data are presently available about the effects of antihypertensive therapy on vascular structure in hypertensive patients with NIDDM. Therefore, we have investigated the effect of an angiotensin-converting enzyme inhibitor, enalapril, and a highly selective angiotensin receptor blocker, candesartan cilexetil, on indices of subcutaneous small resistance artery structure in 15 patients with mild hypertension and NIDDM. Eight patients were treated with candesartan (8 to 16 mg per day) and 7 with enalapril (10 to 20 mg per day) for 1 year. Each patient underwent a biopsy of the subcutaneous fat from the gluteal region at baseline and after 1 year of treatment. Small arteries were dissected and mounted on a micromyograph and the media-to-internal lumen ratio was evaluated; moreover, endothelium-dependent vasodilation to acetylcholine was assessed. A similar blood pressure-lowering effect and a similar reduction of the media-to-lumen ratio of small arteries was observed with the 2 drugs. Vascular collagen content was reduced and metalloproteinase-9 was increased by candesartan, but not by enalapril. Changes of circulating indices of collagen turnover and circulating matrix metalloproteinase paralleled those of vascular collagen. The 2 drugs equally improved endothelial function. In conclusion, antihypertensive treatment with drugs that inhibit the renin-angiotensin-aldosterone system activity is able to correct, at least in part, alterations in small resistance artery structure in hypertensive patients with NIDDM. Candesartan may be more effective than enalapril in reducing collagen content in the vasculature.
Rizzoni
Damiano
D
Department of Medical and Surgical Sciences, University of Brescia, Brescia, Italy. rizzoni@med.unibs.it
Porteri
Enzo
E
De Ciuceis
Carolina
C
Sleiman
Intissar
I
Rodella
Luigi
L
Rezzani
Rita
R
Paiardi
Silvia
S
Bianchi
Rossella
R
Ruggeri
Giuseppina
G
Boari
Gianluca E M
GE
Muiesan
Maria Lorenza
ML
Salvetti
Massimo
M
Zani
Francesca
F
Miclini
Marco
M
Rosei
Enrico Agabiti
EA
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004452:Echocardiography; D004656:Enalapril / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D040521:Subcutaneous Tissue / Q000098:blood supply*; D013777:Tetrazoles / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D004656:Enalapril; D020780:Matrix Metalloproteinase 9; C077793:candesartan cilexetil