Effects of losartan and enalapril on small artery structure in hypertensive rats.
We evaluated the effects on cardiovascular structure of the angiotensin-converting enzyme (ACE) inhibitor enalapril and of the angiotensin II receptor blocker losartan, administered either at hypotensive or nonhypotensive dosage in spontaneously hypertensive rats (SHR). SHR were treated from ages 4 to 12 weeks with low-dose (1 mg x kg(-1) x d(-1)) enalapril, low-dose (0.5 mg x kg(-1) x d(-1)) losartan, high-dose (25 mg x kg(-1) x d(-1)) enalapril, or high-dose (15 mg x kg(-1) x d(-1)) losartan. Untreated WKY and SHR were also studied. Rats were killed at 13 weeks of age, and the heart was weighed. Mesenteric small arteries were dissected and mounted on a micromyograph for determination of media thickness and lumen diameter. In fixed arteries, cell volume, number of cells per segment length, and number of cell layers were measured using the unbiased "disector" method. Systolic blood pressure was significantly reduced by the high doses of both drugs, but the hypotensive effect was greater with enalapril than with losartan (P<0.05). In the high-dose enalapril and losartan groups, there were similar reductions in relative left ventricular mass, media/lumen ratio, and number of cell layers of resistance arteries; however, there were no differences in the cell volume or number of cells per segment length of resistance arteries. Low-dose enalapril did not affect systolic blood pressure or any of the structural parameters. The results show that the hypotensive effects of both losartan and enalapril were associated with outward remodeling of resistance arteries at the cellular level. The effect of losartan on resistance artery structure was equal to that of enalapril, despite the smaller hypotensive effect.
Department of Medical Sciences, University of Brescia, Italy. Damiano.Rizzoni@schering-plough.it
D
D
Rizzoni
E
E
Porteri
A
A
Piccoli
M
M
Castellano
G
G
Bettoni
M L
ML
Muiesan
G
G
Pasini
D
D
Guelfi
M J
MJ
Mulvany
E
E
Agabiti Rosei
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001158:Arteries / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000008:administration & dosage*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology*; D019808:Losartan / Q000008:administration & dosage*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents; D004656:Enalapril; D019808:Losartan