Oxotremorine-induced cerebral hyperemia does not predict infarction volume in spontaneously hypertensive or stroke-prone rats.

Abstract

OBJECTIVES:

We tested the following hypotheses: a) spontaneously hypertensive stroke-prone rats (SHR-SP) have more brain injury than spontaneously hypertensive rats (SHR) and normotensive controls (Wistar-Kyoto rats [WKY]) when exposed to transient focal ischemia; b) infarction size is not correlated with baseline blood pressure; and c) infarction size is inversely related to the cerebral hyperemic response to oxotremorine, a muscarinic agonist that increases cerebral blood flow (CBF) by stimulating endothelial nitric oxide 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 suture technique. Cerebral perfusion, estimated with laser Doppler flowmetry (LD-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-triphenyltetrazolium chloride staining.

MEASUREMENTS AND MAIN RESULTS:

Infarction volume in the striatum of SHR-SP (42+/-4 mm3) was greater than in SHR (29+/-6 mm3) or WKY (1+/-1 mm3) (n = 9 rats/strain). Resting (unanesthetized) mean arterial blood pressure 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). The percentage increase in LD-CBF signal in response to oxotremorine was similar 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 cortex).

CONCLUSIONS:

Although SHR-SP have greater infarction volume than SHR, the mechanism of injury does not appear to be related to a difference in unanesthetized baseline mean arterial blood pressure or to an alteration in endothelium-produced nitric oxide.

• Authors: I Harukuni, H Takahashi, R J Traystman, A Bhardwaj, J R Kirsch
• Journal: Critical care medicine (Crit Care Med) Vol. 28 Issue 1 Pg. 190-5 (Jan 2000) ISSN: 0090-3493 [Print] United States
• PMID: 10667521 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Coloring Agents
• Muscarinic Agonists
• Oxotremorine
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type III
• Nos3 protein, rat

Topics

• Animals
• Brain (blood supply)
• Brain Ischemia (complications, diagnostic imaging, pathology)
• Cerebral Infarction (complications, diagnostic imaging, pathology)
• Coloring Agents
• Disease Models, Animal
• Endothelium, Vascular (drug effects, enzymology)
• Hypertension (complications)
• Laser-Doppler Flowmetry
• Male
• Muscarinic Agonists (pharmacology)
• Nitric Oxide Synthase (drug effects)
• Nitric Oxide Synthase Type III
• Oxotremorine (pharmacology)
• Predictive Value of Tests
• Rats
• Rats, Inbred SHR
• Rats, Inbred Strains
• Rats, Inbred WKY
• Ultrasonography