Stroke Related Alterations in the Cerebrovasculature of spSHR Associated with the Loss of Pressure Dependent Constriction

  • John S. Smeda
Part of the Experimental Biology and Medicine book series (EBAM, volume 26)


Kyoto Wistar stroke prone spontaneously hypertensive rats (spSHR) fed a Japanese style diet containing 4% NaCl from weaning exhibited a 100% mortality associated with hemorrhagic stroke by 20 weeks of age. The middle cerebral arteries (MCA) from spSHR after stroke and at two ages prior to stroke (before and after 12.5 weeks) were sampled and compared to the MCA of age matched stroke resistant SHR (srSHR). When compared to younger spSHR or srSHR the isolated MCA of prestroke spSHR >12.5 weeks exhibited a decreased ability to constrict to a) elevated pressure b) high levels of [K+]0 (84.6 mM) and c) protein kinase C (PKC) activation (10−6M phorbol dibutyrate), whereas the MCA of poststroke spSHR were unable to constrict to the above vasoactive stimuli. Pressure dependent constriction (PDC) of cerebral arteries is associated with smooth muscle cell depolarization, Ca+2 entery into the muscle through voltage gated Ca+2 channels and the activation of PKC. The decreased ability or inability of MCA from spSHR to constrict to depolarizing stimuli (i.e. elevated [K+]0) and PKC activation prior to and after stroke could account for the attenuation or loss of PDC in these arteries. The loss of PDC prior to stroke may promote the over perfusion of the cerebrovasculature and facilitate the formation of hemorrhagic lesions in spSHR.


Middle Cerebral Artery Hemorrhagic Stroke Lumen Diameter Posterior Cerebral Artery Hemorrhagic Lesion 
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  1. 1.
    Brayden, J.E., and G.C. Wellman. Endothelium- dependent dilation of feline cerebral arteries: Role of membrane potential and cyclic nucleotides. J. Cereb. Blood Flow 9: 256–263, 1989.CrossRefGoogle Scholar
  2. 2.
    Halpern, W., G. Osol, and G.S. Coy. Mechanical behavior of pressurized in vitro prearteriolar vessels determined with a video system. Ann. Biomed. Eng. 12: 463–469, 1984.PubMedCrossRefGoogle Scholar
  3. 3.
    Harder, D.R. Pressure-dependent membrane depolarization in cat middle cerebral artery. Circ. Res. 55: 197–202, 1984.PubMedCrossRefGoogle Scholar
  4. 4.
    Laher, I., and J.A. Bevan. Stretch of vascular smooth muscle activates tone and 45 Ca 2+ influx. J. Hypertension 7 (Suppl. 4): S17 - S20, 1989.Google Scholar
  5. 5.
    Laher, I., and J.A. Bevan. Protein kinase C activation selectively augments a stretch-induced, calcium-dependent tone in vascular smooth muscle. J. Pharmacol. Exp. Ther. 242: 566–572, 1987.PubMedGoogle Scholar
  6. 6.
    Loutzenhiser, R., M. Epstein, and C. Horton. Inhibition by diltiazem of pressure-induced afferent vasoconstriction in the isolated perfused rat kidney. Am. J. Cardiol. 59: 72A - 75A, 1987.PubMedCrossRefGoogle Scholar
  7. 7.
    Osol, G. Protein kinase C (PKC) activation lowers the calcium requirements for cerebral artery myogenic tone. J. Vascular Res. 31(Suppl. 1): 37.Google Scholar
  8. 8.
    Osol, G., and W. Halpern. Spontaneous vasomotion in pressurized cerebral arteries from genetically hypertensive rats. Am. J. Physiol. 254: H28 - H33, 1988.PubMedGoogle Scholar
  9. 9.
    Osol, G., I. Laher, and M. Cipolla. Protein kinase C modulates basal myogenic tone in resistance arteries from the cerebral circulation. Circ. Res. 68: 359–367, 1991.PubMedCrossRefGoogle Scholar
  10. 10.
    Nagaoka, A., A. Shino, and H. Iwatsuka. Accelerating effects of dexamethasone and thyroxine on hypertension without accompanying stroke in stroke-prone spontaneously hypertensive rats. Life Sci. 24:71–78, 1979.Google Scholar
  11. 11.
    Smeda, J.S. Cerebral vascular changes asociated with hemorrhagic stroke in hypertension. Can. J. Physíol. Pharmacol. 70: 552–564, 1992.PubMedCrossRefGoogle Scholar
  12. 12.
    Smeda, J.S. Hemorrhagic stroke development in spontaneously hypertensive rats fed a North American, Japanese-style diet. Stroke 20: 1212–1218, 1989.PubMedCrossRefGoogle Scholar
  13. 13.
    Stier, C.S., Jr., I.F. Benter, S. Ahmad, H. Zuo, N. Selig, S. Roethel, S. Levine, and H.D. Itskovitz. Enalapril prevents stroke and kidney dysfunction in salt-loaded stroke-prone spontaneously hypertensive rats. Hypertension (Dallas), 13: 115–121, 1989.CrossRefGoogle Scholar
  14. 14.
    Wang, H., J.S. Smeda, and R.M.K.W. Lee. Preventional stroke and hypertension development in spontaneously hypertensive rats with perindopril treatment. CFBS Meeting, Windsor, Ont., Canada, 1993.Google Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • John S. Smeda
    • 1
  1. 1.Division of Basic Medical Sciences Faculty of MedicineMemorial University of NewfoundlandSt. John’sCanada

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