Developmental course of hypertension and regional cerebral blood flow in stroke-prone spontaneously hypertensive rats.

Abstract

SUMMARY Regional cerebral blood flow (rCBF) was repeatedly measured by the hydrogen clearance method in the frontal cortex of stroke-prone spontaneously hypertensive rats (SHRSP) at the age of 50 days and thereafter. When SHRSP rats developed severe hypertension (over 200 mg Hg at the age of 60 days) rCBF began to decrease abruptly in the frontal cortex -one of the three predilection sites of stroke in these rats. In contrast, such a reduction in rCBF was not noted in either stroke-resistant spontaneously hypertensive rats (SHRSR) which developed moderate hypertension (under 200 mg Hg), or in Wistar-Kyoto rats (WK) with normal blood pressure (under 150 mm Hg).A similar marked reduction of rCBF with severe hypertension (over 200 mm Hg) was also detected in apoplectic gene-free renal infarction hypertensive rats (RHR) experimentally produced from agematched WK animals. Blood samples were obtained through an implanted femoral artery canula without disturbing the nonanesthetized SHRSP, SHRSR and WK rats. Arterial blood gas analysis (PacOj, Pao 2 and pH) showed no significant differences at the age of 5 months in any of these rats.Chemical cerebrovascular reactivity, that is, an increase in rCBF in response to CO a inhalation, showed no significant difference among SHRSP rats from the age of 50 days to 5 months. However, it markedly decreased in SHRSP rats at the age of 9 months and thereafter (the average age of male SHRSP rats which develop stroke is 9 months).The present study showed stroke did not occur in antihypertensive agent-treated SHRSP rats. In these SHRSP rats rCBF did not decrease as long as blood pressure was well-controlled.RECENTLY, there has been increasing clinical interest in studies on cerebral blood flow (CBF) in cerebrovascular disease. Methods for CBF measurement have made rapid progress since the introduction of the nitrous oxide technique, first developed by Kety and Schmidt.1 ' 2 In patients with stroke there have been reported changes in regional cerebral blood flow (rCBF) at various stages. Many investigators have observed rCBF reduction after patients developed stroke. 36 However, the causal relation between CBF and stroke, and especially between CBF and hypertension, have never been elucidated.To clarify this relation, a number of experimental approaches have been tried. "8 Among these, some emphasize clinical data, others add new experimental data and still others have developed new theories, for example, "hypertension breakthrough." 9 ' 10As previously reported, a stroke-prone spontaneously hypertensive rat (SHRSP) was successfully developed in our laboratory at Kyoto University." More than 80% of these SHRSP rats spontaneously develop stroke (cerebral hemorrhage and/or cerebral softening). In our previous report, we confirmed the pathogenetic similarity of stroke in SHRSP rats and humans. 12 In the present studies, using our original SHRSP rats, we tried to elucidate the causal relation between rCBF and stroke.Methods SHRSP rats used in this study were of the A 4 strain among the F^.M...

Tissue Oxygen is Reduced in White Matter of Spontaneously Hypertensive-Stroke Prone Rats: A Longitudinal Study with Electron Paramagnetic Resonance

“…In addition, others have shown a reduction in cerebral blood flow in conjunction with hypertension in SHR/SP with a marked decrease after 12 weeks, which is consistent with the timing we observed in hypoxic changes. [33][34][35] In conclusion, we used the SHR/SP with poor diet and carotid occlusion as a model for WM disease in VCI patients, and showed for the first time using direct pO 2 measurements with EPR a significant reduction in the O 2 in the deep WM. Our results suggest that changes in WM pO 2 may contribute to the selective injury in the deep WM unrelated to frank ischemic infarcts.…”

Regional Cerebral Blood Flow and Arterial Blood Volume and Their Reactivity to Hypercapnia in Hypertensive and Normotensive Rats

“…1,[11][12][13][14] In addition, studies showed that, as compared with normotensive subjects, hypertensive subjects have a blunted CBF response to neural tasks 11 and CO 2 stimulus. 15 In general, the brain maintains adequate CBF within a certain autoregulatory range independent of changes in systemic arterial pressure by adjusting vessel diameters of arteries and arterioles.…”

The expression of matrix metalloproteinase-13 is increased in vessels with blood–brain barrier impairment in a stroke-prone hypertensive model

“…6,7 It is known that the neuronal loss occurs with a reduction of gray matter volume in the CA1 subfield and dentate gyrus of the hippocampus in SHR at the age of 6 months or order, indicating that SHR can be a good animal model of vascular dementia. 8,9 SHRSP is also well known as an excellent model for subcortical vascular dementia accompanied by small-vessel pathology, because these rats show structural alterations of small cerebral arteries, 10 reduction in cerebral blood flow, 11 white matter lesions 12,13 and cognitive impairment. 14,15 We then examined differences in gene expression between microdissected hippocampal vessels with BBB impairment in SHRSP and those without the impairment in Wistar Kyoto (WKY) rats using a microarray assay and reported that the expression of osteopontin, a matricellular protein, was increased in BBB-damaged vessels in hypertensive SHRSP compared with that in vessels without BBB impairment in WKY rats.…”