Oxotremorine-induced cerebral hyperemia does not predict infarction volumein spontaneously hypertensive or stroke-prone rats

Objectives: We tested the following hypotheses: a) spontaneously hypertensi ve stroke-prone rats (SHR-SP) have more brain injury than spontaneously hyp ertensive rats (SHR) and normotensive controls (Wistar-Kyoto rats [WKY]) wh en exposed to transient focal ischemia; b) infarction size is not correlate d with baseline blood pressure; and c) infarction size is inversely related to the cerebral hyperemic response to oxotremorine, a muscarinic agonist t hat increases cerebral blood flow (CBF) by stimulating endothelial nitric o xide synthase, Design: In vivo study. Setting: Animal laboratory in a university teaching hospital. Subjects: Adult age-matched male WKY, SHR, and SHR-SP. Interventions: Rats were instrumented under halothane anesthesia. Transient focal cerebral ischemia was produced for 2 hrs with the intravascular sutu re technique. Cerebral perfusion, estimated with laser Doppler flowmetry (L D-CBF), in response to intravenous oxotremorine, was measured in one cohort of rats to estimate endothelial nitric oxide synthase function. Infarction volume was measured at 22 hrs of reperfusion with 2,3,5-triphenyltetrazoli um chloride staining. Measurements and Main Results: Infarction volume in the striatum of SHR-SP (42 +/- 4 mm(3)) was greater than in SHR (29 +/- mm3) or WKY (1 +/- 1 mm(3) ) (n = 9 rats/strain). Resting (unanesthetized) mean arterial blood pressur e was similar in SHR-SP (177 +/- 5 mm Hg) and SHR (170 +/- 5 mm Hg) despite a greater infarction volume in SHR-SP (n = 4) compared with SHR (n = 5), T he percentage increase in LD-CBF signal in response to oxotremorine was sim ilar for both groups (SHR, 64% +/- 22% [n = 10]; SHR-SP, 69% +/- 22% [n = 8 ]), However, in this cohort, cortical infarction volume was less in SHR (30 % +/- 4% of ipsilateral cortex) than in SHR-SP (49% +/- 2% of ipsilateral c ortex). Conclusions: Although SHR-SP have greater infarction volume than SHR, the m echanism of injury does not appear to be related to a difference in unanest hetized baseline mean arterial blood pressure or to an alteration in endoth elium-produced nitric oxide.