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Stroke prevention by losartan in stroke-prone spontaneously hypertensive rats
Insights
Losartan, an angiotensin II receptor antagonist, prevents stroke and cerebrovascular lesions in hypertensive rats, even without lowering blood pressure. This protective effect is similar to that of ACE inhibitors.
Area of Science:
- Cardiovascular Research
- Hypertension Studies
- Neuroprotection
Background:
- Chronic Angiotensin Converting Enzyme (ACE) inhibitor therapy prevents cerebrovascular lesions in stroke-prone spontaneously hypertensive rats (SHRSP).
- ACE inhibitors have minimal impact on systolic blood pressure in SHRSP.
Purpose of the Study:
- To investigate the effects of losartan, an orally active angiotensin (Ang) II receptor antagonist, on blood pressure and stroke incidence in SHRSP.
- To compare the efficacy of losartan with ACE inhibitors in preventing cerebrovascular lesions.
Main Methods:
- Chronic administration of losartan or vehicle to saline-drinking SHRSP.
- Monitoring of systolic blood pressure and stroke occurrence.
- Radiotelemetric measurement of arterial blood pressure in enalapril-treated SHRSP to assess losartan's effect.
Main Results:
- Oral losartan (30 mg/kg/day) delayed hypertension and prevented stroke in saline-drinking SHRSP.
- Losartan (10 mg/kg/day) prevented cerebrovascular lesions without affecting systolic blood pressure elevation.
- Losartan (30 mg/kg) did not alter blood pressure in SHRSP chronically treated with enalapril.
- Enalapril-treated SHRSP maintained severe hypertension without strokes.
Conclusions:
- Angiotensin II plays a role in the pathophysiology of cerebrovascular lesions in SHRSP.
- Losartan demonstrates a protective action against cerebrovascular lesions in SHRSP, independent of blood pressure reduction.
- Losartan's protective effects are comparable to those of ACE inhibitors.
Background:
Chronic angiotensin converting enzyme (ACE) inhibitor therapy with enalapril, captopril or ceranopril prevents the development of cerebrovascular lesions in stroke-prone spontaneously hypertensive rats (SHRSP) given a 1% NaCl solution to drink, with little or no effect on systolic blood pressure.
Objectives:
To determine the effect of the orally active angiotensin (Ang) II receptor antagonist losartan on blood pressure and stroke in SHRSP.
Methods:
Losartan or vehicle was chronically administered to saline-drinking SHRSP, and systolic blood pressure was monitored. The effect of losartan on arterial blood pressure measured by radiotelemetry in enalapril-treated SHRSP was also examined.
Results:
Oral losartan at 30 mg/kg per day delayed the development of severe hypertension and prevented stroke in saline-drinking SHRSP. Losartan therapy at a dose of 10 mg/kg per day did not affect the systolic blood pressure elevation but prevented the occurrence of cerebrovascular lesions at least until 28 weeks of age. Radiotelemetric monitoring of arterial blood pressure in enalapril-treated, saline-drinking SHRSP over a 3-month period verified the maintenance of severe hypertension without any strokes. Treatment with oral losartan at a dose of 30 mg/kg did not affect the blood pressure of SHRSP chronically treated with enalapril.
Conclusions:
These results are consistent with the theory that Ang II has an effect on the pathophysiology of cerebrovascular lesion development in saline-drinking SHRSP. These findings indicate that losartan has a protective action, similar to that previously observed with ACE inhibitors, against the development of cerebrovascular lesions in SHRSP in the absence of a blood pressure fall.