The effects of captopril treatment on hemorrhagic stroke development in stroke-prone spontaneously hypertensive rats

MacLeod, Andrew B. (2001) The effects of captopril treatment on hemorrhagic stroke development in stroke-prone spontaneously hypertensive rats. Masters thesis, Memorial University of Newfoundland.

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Abstract

We tested the hypothesis that inhibiting stroke development in Kyoto Wistar stroke-prone rats (SHRsp) with captopril treatment (50 mg/kg) was, in part, mediated by reduced plasma aldosterone levels, independent of an antihypertensive effect. -- Plasma aldosterone levels were measured before and after stroke development in untreated and captopril treated SHRsp. Plasma aldosterone levels suppressed by captopril were re-elevated by aldosterone infusion (16 pg/day) into captopril treated SHRsp. The resulting blood pressure (BP) and stroke development was evaluated. We also examined the BP and antistroke effects of a vasodilating agent, hydralazine (40-100 mg/L), and aldosterone antagonism by spironolactone (20 mg/kg). -- Untreated SHRsp developed hypertension and 100% mortality associated with intracerebral hemorrhage by 14 weeks of age. Captopril treatment from 6 weeks of age did not lower BP but increased survival past 35 weeks of age. Hydralazine lowered BP but only mildly retarded stroke development compared with captopril treated rats. Plasma aldosterone levels increased with age in prestrike SHRsp (0.25 to 3.9 nmol/l) and rose further following stroke (11.4 nmol/l). Captopril treated SHRsp showed suppressed aldosterone values (0.5 nmol/l). Restoring hyperaldosteronemia in captopril treated SHRsp negated captopril's ability to retard stroke development. Spironolactone treatment reduced BP with little effect on stroke development. -- Additional studies assessed the hypothesis that captopril treatment helped preserve contractile function (related to blood flow autoregulation) of isolated middle cerebral arteries (MCA) from SHRsp. This was accomplished by examining lumen diameter changes in response to pressure, protein kinase C activation and potassium induced depolarization in the MCA from untreated and captopril treated, pre and post stroke SHRsp. -- Stroke development was associated with a defect in the ability of the MCA to constrict to elevated transmural pressure (pressure dependent constriction) and phorbol dibutyrate induced protein kinase C activation. Captopril treatment preserved these functions. -- We concluded that elevated plasma aldosterone levels promoted stroke development within captopril treated SHRsp through mechanisms not involving mineralocorticoid receptor stimulation or the exacerbation of hypertension. The antistroke effect of captopril may be partially mediated through plasma aldosterone suppression. We further suggest that the ability of captopril treatment to preserve. MCA pressure dependant constriction may also contribute to the antistroke effects of captopril treatment in SHRsp

Item Type: Thesis (Masters)
URI: http://research.library.mun.ca/id/eprint/1487
Item ID: 1487
Additional Information: Bibliography: leaves 161-195
Department(s): Medicine, Faculty of
Date: 2001
Date Type: Submission
Library of Congress Subject Heading: Brain--Hemorrhage--Treatment; Captopril; Hypertension
Medical Subject Heading: Stroke--drug therapy; Intracranial Hemorrhage, Hypertensive--drug therapy; Captopril--drug effects; Aldosterone; Angiotensin-Converting Enzyme Inhibitors;

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