Regression of hypertension-induced vascular hypertrophy by an ACE inhibitor and calcium antagonist in the spontaneously hypertensive rat.
This study was designed to investigate the effects of antihypertensive drugs on vascular hypertrophy and vascular angiotensin II in vivo in spontaneously hypertensive rats (SHR). Hydralazine (10 mg/kg/day), delapril (angiotensin converting enzyme inhibitor; 20 mg/kg/day), manidipine (calcium channel blocker; 10 mg/kg/day), and vehicle were given by gavage to four groups of SHR between 4 and 5 months of age. The aortic angiotensin II level was measured by highly sensitive radioimmunoassay coupled with high pressure liquid chromatography; aortic morphologic studies were performed. Each drug treatment effectively lowered blood pressure to the same level. However, the aortic wall thickness, medial-intimal areas, and wall to lumen ratio of abdominal aorta decreased significantly (p < 0.05, p < 0.01, p < 0.01, respectively) with delapril and manidipine but not hydralazine. Delapril significantly decreased aortic angiotensin II levels (p < 0.05), whereas manidipine treatment significantly increased them (p < 0.05). The aortic angiotensin II level was not changed by hydralazine. These results show that delapril and manidipine caused regression of hypertension-induced vascular hypertrophy in SHR. The probable mechanism of regression of aortic hypertrophy by delapril was inhibition of vascular angiotensin II formation, but the mechanism for manidipine was unclear.
Morishita
R
R
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Higaki
J
J
Nakamura
F
F
Tomita
N
N
Yu
H
H
Nagano
M
M
Mikami
H
H
Ogihara
T
T
D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001012:Aorta, Abdominal / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy*; D006984:Hypertrophy / Q000188:drug therapy / Q000209:etiology; D007189:Indans / Q000494:pharmacology; D008297:Male; D009578:Nitrobenzenes; D010879:Piperazines; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007189:Indans; D009578:Nitrobenzenes; D010879:Piperazines; D000804:Angiotensin II; D006830:Hydralazine; C054218:manidipine; C047759:delapril