Protective effects of delapril, indapamide and their combination on stroke occurrence and lifespan in salt-loaded stroke-prone spontaneously hypertensive rats.
The effects of long-term oral administration of delapril (CAS 83435-67-0), indapamide (CAS 26807-65-8) and their combination on the occurrence of stroke and on mortality were investigated in young salt-loaded stroke-prone spontaneously hypertensive rats (SHRsp) for 31 weeks of treatment (8th-39th week of age) and up to 8 weeks thereafter. Body weight and saline consumption were investigated at regular intervals and cerebrovascular lesions, renal and heart weight were assessed after sacrifice. Untreated SHRsp served as controls. About 50% of control animals died within 6 weeks of saline administration and in 56% of surviving animals cerebral lesions were present at sacrifice, while no death and no cerebral lesions were observed in animals drinking saline, to which delapril, indapamide and their combination had been added, up to the end of treatment. This protective effect was maintained even in the withdrawal period. All treatments induced a highly significant (p < 0.001) reduction of heart weight/body weight and kidney weight/body weight ratios.
Razzetti
R
R
Department of Pharmaco-toxicology, Chiesi Farmaceutici S.p.A., Parma, Italy.
Bongrani
S
S
Oberto
G
G
Ferrari
R
R
Biagini
G
G
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004232:Diuretics / Q000494:pharmacology*; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D007189:Indans / Q000494:pharmacology*; D007190:Indapamide / Q000494:pharmacology*; D008136:Longevity / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D012982:Sodium, Dietary / Q000633:toxicity*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D007189:Indans; D012982:Sodium, Dietary; D007190:Indapamide; C047759:delapril