Quinapril prevents stroke both during and after the treatment period in stroke-prone spontaneously hypertensive rats.
The effects of long-term oral administration of quinapril on the occurrence of stroke and on mortality were investigated in young salt-loaded stroke-prone spontaneously hypertensive rats (SHR-SPs) during the treatment period (8th-34th week of age) and up to 6 weeks thereafter. Simultaneously, blood pressure, saline intake, diuresis, and proteinuria were investigated at regular intervals, and cerebrovascular, renal, and cardiac lesions were assessed after death. Untreated SHR-SPs served as controls. Quinapril completely suppressed stroke and mortality, afforded only limited protection v blood pressure rise, and prevented any increase in saline intake, diuresis, and proteinuria both during and after the treatment period. Quinapril long-lastingly prevented vascular fibrinoid necrosis development at the cerebral, but also at the renal and cardiac levels. In the kidneys, vascular intimal and medial hyperplasia were strongly reduced, as were the glomerular and tubulo-interstitial lesions. At the cardiac level, intimal and medial hyperplasia were slightly reduced but infarction and fibrosis were hardly affected. As the renin-angiotensin system is highly stimulated in SHR-SPs and as angiotensin II (AII) is responsible for fibrinoid necrosis formation, vessel obstruction, and stroke in these animals, we conclude that the long-lasting protection afforded by quinapril v stroke and mortality in SHR-SPs both during and after the treatment period is mostly due to the drug-induced interruption of the renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS)
Vacher
E
E
Département de Pharmacologie, Faculté de Médecine Paris-Sud, France.
Fornes
P
P
Domergue
V
V
Richer
C
C
Bruneval
P
P
Giudicelli
J F
JF
D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001827:Body Height / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000453:epidemiology* / Q000517:prevention & control*; D004231:Diuresis / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D015994:Incidence; D007546:Isoquinolines / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D009206:Myocardium / Q000473:pathology; D011507:Proteinuria / Q000503:physiopathology; D000077583:Quinapril; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D012307:Risk Factors; D044005:Tetrahydroisoquinolines; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000804:Angiotensin II; D000077583:Quinapril