HMG-CoA Reductase Inhibitor Has Protective Effects Against Stroke Events in Stroke-Prone Spontaneously Hypertensive Rats

Abstract

Background and Purpose-Recent clinical studies suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert protective effects against nonhemorrhagic stroke. In a murine cerebral ischemia model produced by occlusion of the middle cerebral artery, statins were shown to reduce infarct size. However, the effect of statins on hypertension-based stroke is unknown. The purpose of this study is to clarify the effect of a statin on stroke in stroke-prone spontaneously hypertensive rats (SHR-SP), in which both cerebral hemorrhage and infarction occur. Methods-We treated SHR-SP chronically from 4 weeks of age with cerivastatin (2 mg/kg per day by gavage) or vehicle.The physiological parameters, the incidence of stroke-associated symptoms, and mortality were assessed. Results-At 14 weeks of age, the incidence (13Ϯ3% versus 37Ϯ8%; PϽ0.01) and the size of stroke (1.6Ϯ0.2 versus 2.2Ϯ0.1 arbitrary units; PϽ0.01) were significantly decreased by cerivastatin, although blood pressure and plasma cholesterol levels were not different. Moreover, stroke-associated symptoms and early mortality of SHR-SP were markedly reduced in the statin-treated group (mortality at the age of 15 weeks: 15% versus 50%; PϽ0.05). Statin treatment significantly reduced superoxide production from nonstroke parenchyma of brain and infiltration of inflammatory cells to the stroke lesions. Conclusions-Our data show that a high dose of statin exerts protection against hypertension-based stroke and ameliorates the disease severity via inhibition of superoxide production and modulation of inflammation in brain.

Renoprotective Effect of Pravastation in Salt-Loaded Dahl Salt-Sensitive Rats

“…In agreement with our data, a previous study reported that pravastatin decreased serum triglycerides but did not affect serum total or HDL cholesterol in SHR (9). The same influence of lipid metabolism has been reported in simvastatin (9) and cerivastatin (40). The different effect of HMG-CoA reductase inhibitors in lipids might be due to the relatively lower levels of serum total, HDL, and LDL cholesterol and the relatively higher level of triglycerides.…”

Statins: another class of antihypertensive agents?

“…Statin treatment significantly reduced superoxide production from non-stroke parenchyma of the brain and infiltration of inflammatory cells to the stroke lesions. 41 In another experimental model of strokeprone SHR, 42 atorvastatin decreased the BP, at least in part via the reduction of sympathetic nervous system activity. This so-called 'sympatho-inhibitory effect' may be mediated by an increase in NO production, with the upregulation of eNOS expression in the brain.…”

“…40 Cerivastatin has also been shown to protect against hypertension-based stroke and ameliorate the disease severity. Kawashima et al 41 showed that chronic treatment of stroke-prone SHR resulted in a significant decrease in the incidence and size of stroke and early mortality. These effects were independent of BP and lipid levels.…”

Correlation of NO Metabolites and 8-Iso-Prostaglandin F 2a With Periventricular Hyperintensity Severity

“…28 In the stroke-prone spontaneously hypertensive rat, which is a model of hypertension-based cerebrovascular injury, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ameliorated the severity of cerebrovascular damage through a reduction of oxidative stress and induction of eNOS activity. 29 In addition to the possible contribution of NO, IsoP itself may be a factor detrimental to WMLs directly because IsoP is a potent vasoactive agent. 15 In this context, it is of interest that a recent study by Brault et al indicated that IsoP injected intraventricularly induced periventricular damage, probably because of microvascular degeneration in rats.…”