Beschreibung:
Obesity is a risk factor for stroke, but the underlying mechanisms by which obesity increases stroke risk are unknown. Hypertension is a major risk factor for stroke. We have previously reported that obese Zucker rats (OZR) have a worse stroke outcome and display evidence of remodeling and increased myogenic tone of the middle cerebral artery (MCA) in parallel with hypertension compared to lean controls (LZR). This study tested the hypothesis that preventing the increase in blood pressure in OZR would improve remodeling, tone, and the outcome of stroke. Blood pressure was measured by telemetery in LZR, OZR, and OZR+hydrochlorthiazide (HCT, 2 mg/kg/day) from the age of 6 to 16 weeks. Vessel structure and function were assessed in isolated, pressurized MCAs. Cerebral schemia was induced for 60 minutes using an intralumenal suture technique, followed by 24 hours of reperfusion. HCT treatment effectively prevented the increase in blood pressure in OZR. Additionally, HCT prevented the changes in MCA structure and tone observed in untreated OZR. Importantly, infarct size was normalized in OZR+HCT following ischemia/reperfusion. These results indicate that increased pressure is essential for driving the changes in infarct size and MCA structure and function in OZR. These observations suggest that increased blood pressure evident in obese individuals is a necessary major determinant for stroke risk in this population.