Structural changes and cyclic GMP content of the aorta after calcium antagonism or angiotensin converting enzyme inhibition in renovascular hypertensive rats.
OBJECTIVE
To evaluate the respective roles of elevated blood pressure and stimulation of the renin-angiotensin system in the development of structural changes in the aortae of rats with renovascular hypertension.


METHODS
Renovascular hypertensive rats (two-kidney, one clip) were randomly allocated to three different groups and were treated with equihypotensive doses of an angiotensin converting enzyme (ACE) inhibitor (enalapril, 3 mg/kg per day) or of a new long-acting calcium antagonist (mibefradil, 30 mg/kg per day). A renovascular hypertensive group was left untreated. A sham-operated group of rats was used as a normotensive control group. At the end of the 5-week treatment period the rats were killed and their aortae were removed. Medial hypertrophy, elastin and collagen content and density of nuclei were evaluated using quantitative morphometry. The aortic cyclic GMP (cGMP) content was quantified by radioimmunoassay.


RESULTS
Hypertension was associated with medial hypertrophy, a decreased elastin: collagen ratio, hypertrophy of the smooth muscle cells and increased cGMP content of the aorta. Mibefradil and enalapril equally prevented the morphological consequences of hypertension (i.e. medial hypertrophy and the decreased elastin:collagen ratio). The aortic cGMP content was increased by enalapril but not by mibefradil.


CONCLUSIONS
The present results show that, even in a high-renin model (two-kidney, one clip), it is possible to prevent or suppress the vascular consequences of hypertension without interfering with the renin-angiotensin system. This suggests that the changes observed in the aorta are directly related to blood pressure or to other mechanisms independent of the renin-angiotensin system, which could be blocked by a calcium antagonist such as mibefradil.
Véniant
M
M
Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Gray
G A
GA
Heudes
D
D
Ménard
J
J
Clozel
J P
JP
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000473:pathology*; D001562:Benzimidazoles / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006152:Cyclic GMP / Q000032:analysis*; D006978:Hypertension, Renovascular / Q000378:metabolism / Q000473:pathology*; D008297:Male; D020748:Mibefradil; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D013764:Tetrahydronaphthalenes; D020748:Mibefradil; D012083:Renin; D006152:Cyclic GMP