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 language | English |
|---|---|
| Pages (from-to) | 1815-1819 |
| Number of pages | 5 |
| Journal | Stroke |
| Volume | 41 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2010 |
| Externally published | Yes |
Fingerprint
Keywords
- cerebral ischemia
- gene knockout mice
- mouse models
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Clinical Neurology
- Advanced and Specialised Nursing
Cite this
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 journal › Article
}
TY - JOUR
T1 - Soluble guanylate cyclase α1β1 limits stroke size and attenuates neurological injury
AU - Atochin, Dmitriy N.
AU - Yuzawa, Izumi
AU - Li, Qian
AU - Rauwerdink, Kristen M.
AU - Malhotra, Rajeev
AU - Chang, Junlei
AU - Brouckaert, Peter
AU - Ayata, Cenk
AU - Moskowitz, Michael A.
AU - Bloch, Kenneth D.
AU - Huang, Paul L.
AU - Buys, Emmanuel S.
PY - 2010/8
Y1 - 2010/8
N2 - 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.
AB - 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.
KW - cerebral ischemia
KW - gene knockout mice
KW - mouse models
UR - http://www.scopus.com/inward/record.url?scp=77955171286&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955171286&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.109.577635
DO - 10.1161/STROKEAHA.109.577635
M3 - Article
C2 - 20595671
AN - SCOPUS:77955171286
VL - 41
SP - 1815
EP - 1819
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 8
ER -