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

2007 ◽  
Vol 292 (1) ◽  
pp. R415-R422 ◽  
Author(s):  
Anne M. Dorrance ◽  
David M. Pollock ◽  
Olga P. Romanko ◽  
David W. Stepp
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Growth Factor ◽  
Infarct Size ◽  
Cerebral Artery ◽  
Vascular Structure ◽  
Hypertensive Rats ◽  
High Potassium ◽  
Wky Rats ◽  
Potassium Supplementation

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-α and -β, 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.

Congenic removal of a QTL for blood pressure attenuates infarct size produced by middle cerebral artery occlusion in hypertensive rats

2007 ◽  
Vol 30 (1) ◽  
pp. 69-73 ◽  
Author(s):  
Hiroshi Yao ◽  
Zong-Hu Cui ◽  
Junichi Masuda ◽  
Toru Nabika
Keyword(s):  
Blood Pressure ◽  
Young Adult ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Infarct Volume ◽  
Chromosome 1 ◽  
Hypertensive Rats ◽  
Arterial Blood ◽  
Mca Occlusion

A genome-wide screen found a blood pressure quantitative trait locus (QTL) on rat chromosome 1 in stroke-prone spontaneously hypertensive rats of a Japanese colony (SHRSP/Izm). In the present study, we investigated the effects of congenic removal of this QTL from SHRSP/Izm on infarct size produced by middle cerebral artery (MCA) occlusion. To establish the congenic strain (SHRSPwch1.0), the blood pressure QTL was introgressed from Wistar-Kyoto (WKY)/Izm to SHRSP/Izm by repeated backcrossing. Male SHRSP/Izm [10–12 wk old (young adult) n = 8, 5 mo old (adult) n = 17] and SHRSPwch1.0 (young adult n = 7, adult n = 15) were randomly assigned to distal MCA occlusion. Resting mean arterial blood pressure (MABP) was 212 ± 23 mmHg in adult SHRSPwch1.0, which was significantly lower than 241 ± 22 mmHg in SHRSP/Izm. Infarct volume in the congenic rats was significantly decreased compared with that in SHRSP/Izm (66.4 ± 21.5 mm3 vs. 103.4 ± 24.8 mm3). Cerebral blood flow (CBF), determined at collaterally-perfused cortex with laser-Doppler flowmetry after MCA occlusion, was significantly greater in adult SHRSPwch1.0 compared with CBF in adult SHRSP/Izm. In young adult rats, there were no significant differences in MABP or in infarct volume between SHRSPwch1.0 and SHRSP/Izm. The congenic removal of a blood pressure QTL lowered blood pressure and caused a substantial reduction in infarct volume (−36%) with increased collateral CBF after MCA occlusion in the congenic rat. We demonstrated for the first time that the congenic strategy is useful to investigate the effects of genetic hypertension on focal ischemia or stroke.

scholarly journals Intact female stroke-prone hypertensive rats lack responsiveness to mineralocorticoid receptor antagonists

2007 ◽  
Vol 293 (4) ◽  
pp. R1754-R1763 ◽  
Author(s):  
Christiné S. Rigsby ◽  
Ashley E. Burch ◽  
Safia Ogbi ◽  
David M. Pollock ◽  
Anne M. Dorrance
Keyword(s):  
Infarct Size ◽  
Cerebral Artery ◽  
Mineralocorticoid Receptor ◽  
Cerebral Vasculature ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Heart Study ◽  
Ischemic Infarct ◽  
Vessel Structure ◽  
Occlusion Technique

Data from the Framingham Heart Study suggest that women may be more sensitive to the deleterious cardiovascular remodeling effects of aldosterone. Previous studies from our laboratory have shown that chronic treatment with spironolactone, a mineralocorticoid receptor (MR) antagonist, decreases ischemic cerebral infarct size and prevents remodeling of the middle cerebral artery (MCA) in male spontaneously hypertensive stroke-prone rats (SHRSP). Therefore, we hypothesized that MR antagonism would reduce ischemic infarct size and prevent MCA remodeling in female SHRSP. Six-week-old female SHRSP were treated for 6 wk with spironolactone (25 or 50 mg·kg−1·day−1) or eplerenone (100 mg·kg−1·day−1) and compared with untreated controls. At 12 wk, cerebral ischemia was induced for 18 h using the intraluminal suture occlusion technique, or the MCA was isolated for analysis of passive structure using a pressurized arteriograph. MR antagonism had no effect on infarct size or passive MCA structure in female SHRSP. To study the potential effects of estrogen, the above experiments were repeated in bilaterally ovariectomized (OVX) female SHRSP treated with spironolactone (25 mg·kg−1·day−1). Infarct size and vessel structure in OVX SHRSP were not different from control SHRSP. Spironolactone had no effect on infarct size in OVX SHRSP. However, MCA lumen and outer diameters were increased in spironolactone-treated OVX SHRSP, suggesting an effect of estrogen. Cerebral artery MR expression, assessed by Western blotting, was increased in female, compared with male, SHRSP. These studies highlight an apparent sexual dimorphism of MR expression and activity in the cerebral vasculature from hypertensive rats.

scholarly journals Tumor necrosis factor-α inhibition attenuates middle cerebral artery remodeling but increases cerebral ischemic damage in hypertensive rats

2014 ◽  
Vol 307 (5) ◽  
pp. H658-H669 ◽  
Author(s):  
Paulo W. Pires ◽  
Saavia S. Girgla ◽  
Guillermo Moreno ◽  
Jonathon L. McClain ◽  
Anne M. Dorrance
Keyword(s):  
Cerebral Ischemia ◽  
Tumor Necrosis Factor ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Tumor Necrosis ◽  
Myogenic Tone ◽  
Hypertensive Rats ◽  
Tnf Α ◽  
Necrosis Factor

Hypertension causes vascular inflammation evidenced by an increase in perivascular macrophages and proinflammatory cytokines in the arterial wall. Perivascular macrophage depletion reduced tumor necrosis factor (TNF)-α expression in cerebral arteries of hypertensive rats and attenuated inward remodeling, suggesting that TNF-α might play a role in the remodeling process. We hypothesized that TNF-α inhibition would improve middle cerebral artery (MCA) structure and reduce damage after cerebral ischemia in hypertensive rats. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with the TNF-α inhibitor etanercept (ETN; 1.25 mg·kg−1·day−1 ip daily) or PBS (equivolume) for 6 wk. The myogenic tone generation, postischemic dilation, and passive structure of MCAs were assessed by pressure myography. Cerebral ischemia was induced by MCA occlusion (MCAO). Myogenic tone was unchanged, but MCAs from SHRSP + ETN had larger passive lumen diameter and reduced wall thickness and wall-to-lumen ratio. Cerebral infarct size was increased in SHRSP + ETN after transient MCAO, despite an improvement in dilation of nonischemic MCA. The increase in infarct size was linked to a reduction in the number of microglia in the infarct core and upregulation of markers of classical macrophage/microglia polarization. There was no difference in infarct size after permanent MCAO or when untreated SHRSP subjected to transient MCAO were given ETN at reperfusion. Our data suggests that TNF-α inhibition attenuates hypertensive MCA remodeling but exacerbates cerebral damage following ischemia/reperfusion injury likely due to inhibition of the innate immune response of the brain.

Abstract 11003: Hypothalamic Activated Microglia With Morphological Changes Accelerate Blood Pressure Elevation During the Hypertension Development Phase in Stroke-prone Spontaneously Hypertensive Rats

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ko Takesue ◽  
Takuya Kishi ◽  
Yoshitaka Hirooka
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Development Phase ◽  
Hypertensive Rats ◽  
Blood Pressure Elevation ◽  
Spontaneously Hypertensive ◽  
Activated Microglia ◽  
Wky Rats ◽  
Pressure Elevation ◽  
Hypertension Development

Introduction: A recent paradigm shift in cardiovascular pathophysiology is the impact of inflammation on hypertension. Inflammation within the paraventricular nucleus of the hypothalamus (PVN) is an important pathology of sympathetic hyperactivity, and is mainly mediated by innate immune cells, microglia. Activated microglia with alteration of their morphology produce inflammatory cytokines. Previous reports demonstrated that microglia within the PVN have activated morphology in angiotensin II-induced hypertensive rats and spontaneously hypertensive rats compared with normotensive control Sprague-Dawley rats or Wistar-Kyoto (WKY) rats. However, the role of activated microglia in the PVN in blood pressure elevation associated with sympathetic hyperactivity remains unknown. In the present study, we determined whether inhibition of microglial activation within the PVN attenuates the blood pressure elevation in genetically hypertensive rats. Methods and Results: We evaluated the activation of PVN microglia, identified by microglia specific ionized calcium-binding adaptor molecule 1 immunoreactivity, by measuring the roundness and the perimeter of microglia at 6 weeks of age, early hypertension development phase in stroke-prone spontaneously hypertensive rats (SHRSP) and compared with them in age-matched normotensive WKY rats. At 6 weeks of age, increased roundness and shortening of perimeter of microglia, indicating activated microglia, were observed in SHRSP compared with those in WKY rats. Then, we performed intracerebroventricular (ICV) administration of minocycline (5 μg/h) to deactivate microglia at 6 weeks of age for 4 weeks. ICV administration of minocycline significantly attenuated systolic blood pressure elevation in SHRSP over 4 weeks (at the end of experiments; 203.2±2.2 mm Hg vs. 215.9±2.7 mm Hg, n=8-9, P<0.05), but not in WKY rats. At 10 weeks of age, morphological analysis revealed that ICV minocycline significantly decreased the roundness and increased the perimeter of microglia, indicating deactivation of microglia, within the PVN in SHRSP. Conclusions: Hypothalamic activated microglia with morphologic changes accelerate blood pressure elevation during the hypertension development phase in SHRSP.

High-potassium diet attenuates salt-induced acceleration of hypertension in SHR

1991 ◽  
Vol 260 (1) ◽  
pp. R21-R26 ◽  
Author(s):  
Y. Sato ◽  
K. Ando ◽  
E. Ogata ◽  
T. Fujita
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
High Potassium ◽  
Spontaneously Hypertensive ◽  
Antihypertensive Action ◽  
High K ◽  
Wistar Kyoto ◽  
Renal Vascular

We studied the effects of K supplementation (8% KCl) for 4 wk on blood pressure (BP), Na space, and renal hemodynamics in 5-wk-old, spontaneously hypertensive rats (SHR) or age-matched Wistar-Kyoto rats (WKY) eating normal-NaCl (0.66%) or high-NaCl (8%) diet. In WKY, high-Na and/or high-K diets had no effects on BP. In SHR, Na load accelerated the development of hypertension, whereas K supplementation did not affect BP of normal-Na SHR but attenuated the increase in BP with Na load. Correspondingly, Na load in SHR significantly increased renal vascular resistance (RVR), and K supplementation attenuated the increased RVR of Na-loaded SHR. Moreover, Na space of SHR was increased compared with that of WKY, and although Na load did not affect Na space, K supplementation tended to decrease Na space in SHR. These results indicate that 9-wk-old SHR is relatively volume-expanded compared with age-matched WKY, and K supplementation could improve the lowered slope of the pressure-Na excretion relationship in SHR, resulting in maintenance of Na balance. Thus the data suggest that changes in RVR, which might be intimately related to renal function for Na excretion, contribute to both salt sensitivity of SHR and antihypertensive action of K supplementation in Na-loaded SHR.

scholarly journals Effect of a methionine-supplemented diet on the blood pressure of Wistar–Kyoto and spontaneously hypertensive rats

2003 ◽  
Vol 89 (4) ◽  
pp. 539-548 ◽  
Author(s):  
Sophie Robin ◽  
Véronique Maupoil ◽  
Frédérique Groubatch ◽  
Pascal Laurant ◽  
Alain Jacqueson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Plasma Homocysteine ◽  
Shr Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Complex Interactions ◽  
Methionine Concentration ◽  
Wistar Kyoto

The objectives of the present work were to evaluate the effect of a methionine-supplemented diet as a model of hyperhomocysteinaemia on the systolic blood pressure (BP) and vasomotor functions of aortic rings in Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR). WKY and SHR rats, randomised into four groups, were fed a normal semisynthetic diet or a methionine (8 g/kg)-supplemented diet for 10 weeks. Systolic BP was measured non-invasively. At the end of the experiment, plasma homocysteine, methionine, cysteine and glutathione levels were determined. Vasoconstriction and vasodilatation of aortic rings were measured. The methionine-supplemented diet induced a significant increase in plasma homocysteine and methionine concentration in both WKY and SHR rats, an increase in plasma cysteine concentrations in WKY rats and an increase in the glutathione concentration in SHR. The systolic BP of WKY rats fed the methionine-supplemented diet increased significantly (P<0·01), whereas systolic BP was reduced in SHR. An enhanced aortic responsiveness to noradrenaline and a decreased relaxation induced by acetylcholine and bradykinin were observed in the WKY rats fed the methionine-enriched diet. In SHR, the bradykinin-induced relaxation was reduced, but the sodium nitroprusside response was increased. In conclusion, a methionine-enriched diet induced a moderate hyperhomocysteinaemia and an elevated systolic BP in WKY rats that was consistent with the observed endothelial dysfunction. In SHR, discrepancies between the decreased systolic BP and the vascular alterations suggest more complex interactions of the methionine-enriched diet on the systolic BP. Further investigations are needed to understand the paradoxical effect of a methionine-rich diet on systolic BP.

scholarly journals Effects of physical training and potassium supplementation on blood pressure, glucose metabolism and albuminuria of spontaneously hypertensive rats

2014 ◽  
Vol 36 (3) ◽  
Author(s):  
Evelyn Manuella Martins Gomes Jodas ◽  
Aline Francisco Voltera ◽  
Milton Ginoza ◽  
Osvaldo Kohlmann Junior ◽  
Nelson Brancaccio dos Santos ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glucose Metabolism ◽  
Physical Training ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Potassium Supplementation
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