Effect of hypertension and peroxynitrite decomposition with FeTMPyP on CBF and stroke outcome.
We investigated the effect of peroxynitrite decomposition catalyst FeTMPyP treatment on perfusion deficit, vascular function and stroke outcome in Wistar ( n = 26) and spontaneously hypertensive rats stroke-prone (SHRSP; n = 26) that underwent tMCAO for 2 h or Sham operation. Peri-infarct CBF was measured by hydrogen clearance in the absence or presence of FeTMPyP (10 mg/kg, i.v.) or vehicle 10 min before reperfusion. Myogenic tone of parenchymal arterioles (PAs) was measured as an indication of small vessel resistance (SVR). Baseline CBF was similar between Wistar and SHRSP (114 ± 12 vs. 132 ± 9 mL/100 g/min); however, MCAO caused greater perfusion deficit in SHRSP (24 ± 6 vs. 7 ± 1 mL/100 g/min; p < 0.05) and increased infarct volume by TTC (12 ± 6 vs. 32 ± 2%; p < 0.05). Reperfusion CBF was decreased from baseline in both SHRSP and Wistar (54 ± 16 and 46 ± 19 mL/100 g/min; p < 0.05), suggesting increased infarction in SHRSP was related to greater perfusion deficit. PAs from SHRSP had increased tone vs. Wistar that was enhanced after tMCAO. FeTMPyP treatment did not affect CBF during ischemia or reperfusion, or tone of PAs, but decreased the incidence of hemorrhage in SHRSP by 50%. Thus, increased tone in PAs from SHRSP could increase perfusion deficit during MCAO that was not alleviated by FeTMPyP.
Departments of Neurological Sciences, Obstetrics, Gynecology & Reproductive Sciences, and Pharmacology, University of Vermont College of Medicine, Burlington, VT, USA.
Marilyn J
MJ
Cipolla
Departments of Neurological Sciences, Obstetrics, Gynecology & Reproductive Sciences, and Pharmacology, University of Vermont College of Medicine, Burlington, VT, USA.
Julie G
JG
Sweet
Departments of Neurological Sciences, Obstetrics, Gynecology & Reproductive Sciences, and Pharmacology, University of Vermont College of Medicine, Burlington, VT, USA.
Siu-Lung
SL
Chan
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D030421:Peroxynitrous Acid / Q000378:metabolism*; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020521:Stroke / Q000378:metabolism / Q000503:physiopathology*
C492721:5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato-iron(III); D008665:Metalloporphyrins; D030421:Peroxynitrous Acid
Arterioles; cerebral blood flow; focal ischemia; hypertension; reperfusion