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 (13+/-3% versus 37+/-8%; P<0.01) and the size of stroke (1.6+/-0.2 versus 2.2+/-0.1 arbitrary units; P<0.01) 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%; P<0.05). 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.

• Authors: Seinosuke Kawashima, Tomoya Yamashita, Yoichi Miwa, Masanori Ozaki, Masayuki Namiki, Tetsuaki Hirase, Nobutaka Inoue, Ken-ichi Hirata, Mitsuhiro Yokoyama
• Journal: Stroke (Stroke) Vol. 34 Issue 1 Pg. 157-63 (Jan 2003) ISSN: 1524-4628 [Electronic] United States
• PMID: 12511768 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Lipids
• Pyridines
• Superoxides
• cerivastatin
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type III
• Nos3 protein, rat

Topics

• Animals
• Blood Pressure (drug effects)
• Blood Vessels (enzymology)
• Brain (pathology)
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology, therapeutic use)
• Hypertension (complications, physiopathology)
• Inflammation (pathology)
• Kinetics
• Lipids (blood)
• Male
• Nitric Oxide Synthase (metabolism)
• Nitric Oxide Synthase Type III
• Pyridines (pharmacology, therapeutic use)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Stroke (diagnosis, metabolism, prevention & control)
• Superoxides (metabolism)
• Survival Analysis