Soluble guanylate cyclase α1β1 limits stroke size and attenuates neurological injury

Dmitriy N. Atochin, Izumi Yuzawa, Qian Li, Kristen M. Rauwerdink, Rajeev Malhotra, Junlei Chang, Peter Brouckaert, Cenk Ayata, Michael A. Moskowitz, Kenneth D. Bloch, Paul L. Huang, Emmanuel S. Buys

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background and Purpose-: Nitric oxide mediates endothelium-dependent vasodilation, modulates cerebral blood flow, and determines stroke outcome. Nitric oxide signals in part by stimulating soluble guanylate cyclase (sGC) to synthesize cGMP. To study the role of sGC in stroke injury, we compared the outcome of cerebral ischemia and reperfusion in mice deficient in the α1 subunit of sGC (sGCα1-/-) with that in wild-type mice. Methods-: Blood pressure, cerebrovascular anatomy, and vasoreactivity of pressurized carotid arteries were compared in both mouse genotypes. Cerebral blood flow was measured before and during middle cerebral artery occlusion and reperfusion. We then assessed neurological deficit and infarct volume after 1 hour of occlusion and 23 hours of reperfusion and after 24 hours of occlusion. Results-: Blood pressure and cerebrovascular anatomy were similar between genotypes. We found that vasodilation of carotid arteries in response to acetylcholine or sodium nitroprusside was diminished in sGCα 1-/- compared with wild-type mice. Cerebral blood flow deficits did not differ between the genotypes during occlusion, but during reperfusion, cerebral blood flow was 45% less in sGCα1 -/- mice. Infarct volumes and neurological deficits were similar after 24 hours of occlusion in both genotypes. After 1 hour of ischemia and 23 hours of reperfusion, infarct volumes were 2-fold larger and neurological deficits were worse in sGCα1 than in the wild-type mice. Conclusion-: sGCα1 deficiency impairs vascular reactivity to nitric oxide and is associated with incomplete reperfusion, larger infarct size, and worse neurological damage, suggesting that cGMP generated by sGCα 1β1 is protective in ischemic stroke.

Original languageEnglish
Pages (from-to)1815-1819
Number of pages5
JournalStroke
Volume41
Issue number8
DOIs
Publication statusPublished - Aug 2010
Externally publishedYes

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Cerebrovascular Circulation
Reperfusion
Stroke
Wounds and Injuries
Genotype
Nitric Oxide
Carotid Arteries
Vasodilation
Anatomy
Blood Pressure
Middle Cerebral Artery Infarction
Nitroprusside
Brain Ischemia
Acetylcholine
Endothelium
Blood Vessels
Soluble Guanylyl Cyclase
Ischemia

Keywords

  • cerebral ischemia
  • gene knockout mice
  • mouse models

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialised Nursing

Cite this

Atochin, D. N., Yuzawa, I., Li, Q., Rauwerdink, K. M., Malhotra, R., Chang, J., ... Buys, E. S. (2010). Soluble guanylate cyclase α1β1 limits stroke size and attenuates neurological injury. Stroke, 41(8), 1815-1819. https://doi.org/10.1161/STROKEAHA.109.577635

Soluble guanylate cyclase α1β1 limits stroke size and attenuates neurological injury. / Atochin, Dmitriy N.; Yuzawa, Izumi; Li, Qian; Rauwerdink, Kristen M.; Malhotra, Rajeev; Chang, Junlei; Brouckaert, Peter; Ayata, Cenk; Moskowitz, Michael A.; Bloch, Kenneth D.; Huang, Paul L.; Buys, Emmanuel S.

In: Stroke, Vol. 41, No. 8, 08.2010, p. 1815-1819.

Research output: Contribution to journalArticle

Atochin, DN, Yuzawa, I, Li, Q, Rauwerdink, KM, Malhotra, R, Chang, J, Brouckaert, P, Ayata, C, Moskowitz, MA, Bloch, KD, Huang, PL & Buys, ES 2010, 'Soluble guanylate cyclase α1β1 limits stroke size and attenuates neurological injury', Stroke, vol. 41, no. 8, pp. 1815-1819. https://doi.org/10.1161/STROKEAHA.109.577635
Atochin, Dmitriy N. ; Yuzawa, Izumi ; Li, Qian ; Rauwerdink, Kristen M. ; Malhotra, Rajeev ; Chang, Junlei ; Brouckaert, Peter ; Ayata, Cenk ; Moskowitz, Michael A. ; Bloch, Kenneth D. ; Huang, Paul L. ; Buys, Emmanuel S. / Soluble guanylate cyclase α1β1 limits stroke size and attenuates neurological injury. In: Stroke. 2010 ; Vol. 41, No. 8. pp. 1815-1819.
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AU - Malhotra, Rajeev

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AU - Ayata, Cenk

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AU - Buys, Emmanuel S.

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