BACKGROUND: High incidence of stroke at interchange period of autumn and winter was demonstrated by epidemiological survey, and the specific causes should be further investigated.OBJECTIVE: To investigate the influence of artificial cold exposure on the incidence of stroke in renovascular hypertensive rats (RHR), and analyze the association with blood pressure and cold-inducible RNA binding protein (CIRP) mRNA expression in brain tissue.DESIGN: A completely randomized grouping design, a randomized control animal trial.SETTINGS: Lab of Neurology, the First Affiliated Hospital of Sun Yat-sen University; Department of Chemistry, Open laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong.MATERIALS: Male SD rats (n =460), weighing 80- 100 g were obtained from Guangdong Province Health Animal Unit. A modified RXZ-300A intelligent artificial climate cabinet (Ningbo Jiangnan Instrument Co.,Ltd., China).METHODS: The experiment were processed in the Lab of Neurology, the First Affiliated Hospital of Sun Yat-sen University and the Open Laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong from October 2004 to November 2005. Rats (n =400) were operated to establish 2-kidney 2-clip RHR model as described previously. The sham-operated rats (n =60) served as normotensive controls. Eight weeks later, 300 of RHR were randomly selected according to their systolic blood pressure (SBP) and divided into 3 sub-groups (n =100 per group): mild hypertensive group (SBP of 160 - 200 mm Hg), moderate hypertensive group (SBP of 200 - 220 mm Hg) and severe hypertensive group (SBP ＞ 220 mm Hg). Each group was further divided into two groups (n =50) under ACE and non-ACE. Normal sham-operated SD rats (n =60), SBP ＜ 140 mm Hg, were randomly divided into two groups: Sham-operated control group (n =30) under ACE and non-ACE. To establish the ACE and non-ACE treatment, rats were housed individually in artificial climate cabinet, and ACE was designed as three cycles of 12-hour light of 22 ℃ (7∶00 - 19∶00) and 12-hour dark of 4 ℃(19∶ 00 - 7∶ 00). The non-ACE group was kept at 22 ℃ throughout the experiment.MAIN OUTCOME MEASURES: Blood Pressure changes were measured and stroke symptom were observed; Expression of the CIRP were examined by reverse transcription-polymerase chain reaction.RESULTS: Finally 360 rats were involved in the analysis of results. ① Incidence of stroke: The incidence of stroke in 2k2c RHR was significantly higher after a three-day intermittent (12-hour) ACE (29.3%) as compared with that in non-ACE (17.3%) (P ＜ 0.05). Furthermore, the severe hypertensive 2k2c RHR (BP ＞ 220 mm Hg) was found to have much higher incidence of stroke (66%, 33/50) than the mild (8%, 4/50) and moderate (18%) hypertensive 2k2c RHR. ② CIRP mRNA in brain tissue: ACE treatment stimulated the mRNA expression of CIRP in non-stroke 2k2c RHR but not in stroke 2k2c RHR (P ＜ 0.05).CONCLUSION: High blood pressure and low expression of CIRP are associated with ACE induced stroke.