Obesity Increases Blood Pressure, Cerebral Vascular Remodeling, and Severity of Stroke in the Zucker Rat

Abstract

Obesity is a risk factor for stroke, but the mechanisms by which obesity increases stroke risk are unknown. Because microvascular architecture contributes to the outcome of stroke, we hypothesized that middle cerebral arteries (MCA) from obese Zucker rats (OZR) undergo inward remodeling and develop increased myogenic tone compared to lean Zucker rats (LZR). We further hypothesized that OZR have an increased infarct following cerebral ischemia and that changes in vascular structure and function correlate with the development of hypertension in OZR. Blood pressure was measured by telemetery in LZR and OZR from 6 to 17 weeks of age. Vessel structure and function were assessed in isolated MCAs. Stroke damage was assessed after ischemia was induced for 60 minutes followed by 24 hours of reperfusion. While mean arterial pressure (MAP) was similar between young rats (6-8 weeks old), MAP was higher in adult (14-17 weeks old) OZR than LZR. MCAs from OZR had a smaller lumen diameter and increased myogenic vasoconstriction compared to those from LZR. Following ischemia, infarction was 58% larger in OZR than LZR. Prior to the development of hypertension, MCA myogenic reactity and lumen diameter as well as infarct size were similar between young LZR and OZR. Our results indicate that the MCAs of OZR undergo structural remodeling and that these rats have greater cerebral injury following cerebral ischemia. These cerebrovascular changes correlate with the development of hypertension and suggest that the increased blood pressure may be the major determinant for stroke risk in obese individuals.

Altered regulation of the rostral ventrolateral medulla in hypertensive obese Zucker rats

“…Baseline MAP of the OZR was significantly higher than the LZR under urethane anesthesia (Table 1), as previously reported for conscious adult Zucker rats (5,29). Rectified SNA voltage was also significantly higher in the OZR compared with the LZR (Table 1), in agreement with previous observations of elevated renal and splanchnic SNA in the OZR (16,27).…”

Differential structural and functional changes in penile and coronary arteries from obese Zucker rats

“…Accordingly, in the present study, structural abnormalities were associated with severe endothelial dysfunction in PAs, whereas structure was preserved in CAs, which displayed a moderate endothelial dysfunction in the same OZRs. Interestingly, PA vascular reactivity and structure were impaired before the onset of hypertension and in contrast to that recently reported for cerebral arteries in this animal model, where structural remodeling, enhanced myogenic tone, and increased stroke risk and injury correlate with the development of hypertension (37). Our findings in PAs of OZRs therefore reinforce the view of ED as an early sign of subclinical vascular disease (46).…”

Modeling Risk Factors and Confounding Effects in Stroke

“…However, our own experience suggests that despite marginally extended surgery times, subcutaneous adiposity does not unduly affect success rates. This is also borne out by the recent studies that have emerged combining experimental obesity and stroke (119)(120)(121)(122). All such studies have found that the severity of brain damage is markedly increased in obese rodents compared to corresponding wild-types (see below).…”

“…It is only in the last 2 years that studies investigating the impact of obesity on experimental stroke in rodents have emerged (119)(120)(121)(122). All studies have found significantly increased ischemic brain damage in the obese group (see Table).…”