Preserved glycemic control and baroreflex efficacy in young adult hypertensive female obese Zucker rats

Abstract

Obese Zucker rats (OZRs) develop hypertension and hyperinsulinemia by 3 months of age. Male OZRs also have diminished baroreflex-mediated activation of nucleus tractus solitarius (NTS) and bradycardia, which are improved by correcting their hyperglycemia. Conversely, 3-month-old female OZRs and lean Zucker rats (LZRs) have equivalent baroreflex-mediated bradycardia that is impaired in 6-month-old OZRs. We hypothesized that 3-month-old female OZRs maintain NTS activation and baroreflexes coincident with glycemic control. We also hypothesized that 6-month-old female OZRs develop impaired baroreflexes with hyperglycemia and diminished NTS activation. In 12-16-week-old females, sympathetic nerve activity (SNA) and arterial pressure (AP) were higher in OZRs than LZRs. However, baroreflex-mediated inhibition of SNA and bradycardia were equivalent in female OZRs and LZRs. Unlike deficits in male OZRs, female OZRs and LZRs had no differences in phenylephrine-induced c-Fos expression in NTS or decreases in SNA and AP evoked by glutamate into NTS. Compared to hyperglycemia in male OZRs (217.9±34.4mg/dl), female OZRs had normal fed blood glucose levels (108.2±1.6mg/dl in LZRs and 113.6±3.5mg/dl in OZRs) with emerging glucose intolerance. Conscious 24-27-week-old female OZRs had impaired baroreflex-mediated bradycardia, but fed blood glucose was modestly elevated (124.2±5.2mg/dl) and phenylephrine-induced c-Fos expression in NTS was comparable to LZRs. These data suggest better glycemic control in 3-month-old female OZRs prevents diminished NTS activation and baroreflexes, supporting the notion that hyperglycemia impairs these responses in male OZRs. However, 6-month-old female OZRs had impaired baroreflex efficacy without diminished NTS activation or pronounced hyperglycemia, suggesting baroreflex deficits develop by different mechanisms in female and male OZRs.