Effects of enalapril and amlodipine on small-artery structure and composition, and on endothelial dysfunction in spontaneously hypertensive rats.
OBJECTIVE
To determine whether an angiotensin converting enzyme inhibitor, enalapril, and a dihydropyridine calcium channel antagonist, amlodipine, regress the altered structure, media composition, and vascular relaxation of small arteries of spontaneously hypertensive rats.


METHODS
Spontaneously hypertensive rats aged 10 weeks were treated for 12 weeks with 10 mg/kg per day enalapril or 10-20 mg/kg per day amlodipine and compared with age-matched untreated spontaneously hypertensive rats. Small coronary, renal, mesenteric, and femoral arteries (lumen diameter 200-250 microm) were studied isometrically on a wire myograph, and mesenteric arteries isobarically as pressurized vessels. The composition of the vascular media of the latter was studied by electron microscopy.


RESULTS
Blood pressure, and cardiac and aortic hypertrophy were reduced in treated spontaneously hypertensive rats. Treatment significantly decreased media thickness and media: lumen ratio of coronary, renal, mesenteric, and femoral small arteries studied isometrically and of pressurized mesenteric small arteries. Media cross-sectional area was smaller for coronary arteries studied isometrically and mesenteric arteries studied isobarically. Electron microscopic analysis revealed an increase in collagen: elastin ratio in the media of spontaneously hypertensive rat vessels, and a decrease under treatment to levels found in Wistar-Kyoto rats, with no significant changes detected in smooth muscle cells. The amplitude of contractions induced by acetylcholine on wire-myograph-mounted mesenteric arteries from spontaneously hypertensive rats were decreased by treatment, and relaxation of pressurized arteries induced by acetylcholine was normalized.


CONCLUSIONS
Treatment of spontaneously hypertensive rats with enalapril or with amlodipine resulted in regression of cardiovascular hypertrophy and amelioration of endothelial dysfunction. Morphometric results obtained using an isometric myograph and a pressurized preparation to study rat small arteries were closely correlated. Regression of structural remodeling in small arteries was outward hypotrophic, with a reduction in the collagen: elastin ratio, and without net change in the absolute and relative volumes of smooth muscle and number of smooth muscle layers.
Sharifi
A M
AM
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montréal, University of Montréal, Québec, Canada.
Li
J S
JS
Endemann
D
D
Schiffrin
E L
EL
D017311:Amlodipine / Q000494:pharmacology* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001158:Arteries / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D004656:Enalapril / Q000494:pharmacology* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D017311:Amlodipine; D004656:Enalapril