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(Stroke. 2007;38:1590.)
© 2007 American Heart Association, Inc.

Original Contributions

Effects of Poststroke Losartan Versus Captopril Treatment on Myogenic and Endothelial Function in the Cerebrovasculature of SHRsp

From the Division of Basic Medical Sciences Memorial University, St. John’s, Newfoundland, Canada.

Correspondence to Dr J.S. Smeda, PhD, Division of Basic Medical Sciences, Room H4354, Memorial University, Health Science Center, St John’s, Newfoundland, Canada, A1B 3V6. E-mail jsmeda{at}mun.ca

Background and Purpose— We assessed the ability of poststroke captopril and losartan treatment to reverse myogenic and endothelial dysfunction in the middle cerebral arteries of Kyoto-Wistar stroke-prone spontaneously hypertensive rats (SHRsp) that developed intracerebral hemorrhagic stroke.

Methods— SHRsp were sampled before and after stroke development and after up to 37 days of captopril (50 mg/kg per day) or losartan (35 mg/kg per day) treatment initiated after stroke. Pressure-dependent constriction to a 100-mm Hg pressure step, constriction to nitric oxide synthase inhibition (100 µmol/L N-nitro-L-arginine methyl ester), and endothelium-dependent vasodilation to bradykinin (1.6 µmol/L), 2-f-LIGRLO-NH₂ (1 µmol/L, a protease-activated receptor-2 agonist), and A23187 (2 µmol/L) were evaluated in middle cerebral arteries at 100 mm Hg with a pressure myograph.

Results— Middle cerebral arteries from SHRsp with stroke could not constrict to pressure or nitric oxide synthase inhibition, lacked the ability to vasodilate to bradykinin, and exhibited attenuated dilation and vasomotion in response to A23187. Vasodilation to 2-f-LIGRLO-NH₂ was unaltered. The aforementioned cerebrovascular alterations were reversed after 31 days of poststroke losartan but not of captopril treatment in the absence of an antihypertensive effect. Captopril treatment restored middle cerebral artery constriction to pressure, NOS inhibition, and bradykinin vasodilation temporarily after 7 to 18 days of treatment, after which function deteriorated to a level observed in SHRsp at stroke.

Conclusions— Aspects of poststroke cerebrovascular dysfunction, which likely play an important role in altering and modulating cerebral blood flow autoregulation, can be reversed in SHRsp more effectively after stroke development by blocking angiotensin II type 1 receptors as opposed to lowering angiotensin II levels.

Key Words: captopril • endothelium • intracerebral hemorrhage • myogenic response • SHRsp