A high-potassium diet reduces infarct size and improves vascular structure in hypertensive rats

Abstract

High-potassium diets can improve vascular function, yet the effects of potassium supplementation on ischemic stroke have not been studied. We hypothesized that dietary potassium supplementation would reduce ischemic cerebral infarct size by reversing cerebral artery hypertrophy. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were fed diets containing 0.79% potassium (LK) or 2.11% potassium (HK) for 6 wk; Wistar-Kyoto (WKY) rats were fed the LK diet. The HK diet did not reduce blood pressure, as measured by telemetry, in the SHRSP. Cerebral ischemia was induced by middle cerebral artery (MCA) occlusion. The resultant infarct was smaller in the HK-SHRSP than in the LK-SHRSP: 55.1 +/- 6.3 vs. 71.4 +/- 2.4% of the hemisphere infarcted (P < 0.05). Infarcts were smaller in WKY rats (33.5 +/- 4.8%) than in LK-SHRSP or HK-SHRSP. The vessel wall of MCAs from LK-SHRSP was hypertrophied compared with WKY rats; this was reversed in HK-SHRSP. RT-PCR analysis of the cerebral vessels showed that expression of platelet-derived growth factor receptors-alpha and -beta, epidermal growth factor receptor, and collagen I and III was increased in the vessels from LK-SHRSP compared with WKY rats and reduced in HK-SHRSP. These results suggest that potassium supplementation provides neuroprotection in a model of ischemic stroke independent of blood pressure and possibly through changes in vascular structure.

Doxycycline, a matrix metalloprotease inhibitor, reduces vascular remodeling and damage after cerebral ischemia in stroke-prone spontaneously hypertensive rats

“…With very few available options for the treatment of stroke, to reduce stroke risk it seems prudent to identify therapies aimed at primary prevention. We have shown previously that improving MCA structure reduces the damage caused by cerebral ischemia (13,41,42). In the present report, we show that chronic DOX treatment attenuates the hypertensive vascular remodeling observed in SHRSP.…”

“…Many studies show that the MCA from hypertensive animals undergoes inward remodeling, which includes a reduction in lumen diameter (13,14,22,25,41). This process begins in hypertensive rats early in the development of the disease (26).…”

“…13,14,38,42). Remodeling of the resistance vasculature encompasses structural changes that lead to a reduction in the lumen diameter and an increase in the wall thickness and wall-to-lumen ratio (2,17,23,36).…”

“…Together, these alterations may lead to impairment in the ability of vessels to autoregulate and dilate. In the cerebral vasculature, these impairments might cause a reduction in blood flow and an increase in ischemic damage (13). When one considers attenuation of vascular remodeling as a primary strategy for stroke prevention, it is important to identify agents that have a maximal effect on the cerebral vasculature and little effect on the periphery, to not decrease blood pressure or impair its control.…”

Spironolactone improves structure and increases tone in the cerebral vasculature of male spontaneously hypertensive stroke-prone rats

“…The differences in vessel structure also do not appear to be related to overall growth, as body weight was not changed by treatment with spironolactone. Other circulating factors, such as plasma potassium (Dorrance et al, 2006a), can also have effects on the outcome of ischemic stroke. However, plasma potassium is not significantly elevated in the spironolactone-treated SHRSP, indicating that the effects of spironolactone are most likely through the inhibition of the mineralocorticoid receptor and not due to increased plasma potassium.…”