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

Figure 1.. Baseline mean arterial pressure (AP) and baroreflex-mediated bradycardia in conscious 12- to 14-wk-old female and male lean Zucker rats (LZRs) and obese Zucker rats (OZRs). Individual data points are shown with a red horizontal line representing the mean and capped vertical lines representing the SE. A: baseline mean AP immediately preceding the infusion of phenylephrine (PE) in female rats (n = 6 LZRs and 6 OZRs) and male rats (n = 6 LZRs and 5 OZRs). B: representative recordings of mean AP (MAP), AP, and heart rate (HR) from a female OZR with infusion of PE. C: maximum PE-induced decreases in HR in first 5 min of the 40 mmHg rise in AP in rats from A. Males and females were analyzed separately by unpaired t tests. *P <0.05, OZRs vs. LZRs of same sex.

Figure 2.. Phenylephrine (PE)-induced c-Fos expression in the nucleus tractus solitarius (NTS) in conscious 12- to 14-wk-old female and male Zucker rats. Individual data points are shown with a red horizontal line representing the mean and capped vertical lines representing the SE. Data are from rats in Fig. 1 and include three additional female rats that were not included in Fig. 1 due to unstable heart rate (HR) readings during the first 5 min of the PE infusion. A: counts of c-Fos+ neurons in the NTS of females at four rostro-caudal levels from bregma (n = 8 LZRs and 7 OZRs). B: counts of c-Fos+ neurons in the NTS of males at the same four rostro-caudal levels shown in A (n = 6 LZRs and 5 OZRs). C: total counts of c-Fos+ neurons in the NTS from females and males in A and B. D: representative maps of c-Fos+ neurons in the NTS at four rostro-caudal levels from bregma in a female LZR (left map inset), a female OZR (middle map inset), and a male OZR (right map inset), as previously reported in male OZRs and LZRs (33). Representative photomicrographs of c-Fos immunohistochemistry from the four groups are in Fig. 3. Males and females were analyzed separately by two-way ANOVA with repeated…

Figure 3.. Representative photomicrographs of phenylephrine (PE)-induced c-Fos expression in the nucleus tractus solitarius (NTS) of 12- to 14-wk-old male and female obese Zucker rats (OZRs) and lean Zucker rats (LZRs). The 30-μm sections are in the coronal plane, showing the right half of intermediate NTS at bregma level: 13.8 mm in a male LZR (A), a male OZR (B), a female LZR (C), and a female OZR (D), as previously shown in males (33, 38). AP, area postrema; F-LZR, female LZR; F-OZR, female OZR; M-LZR, male LZR; M-OZR, male OZR; TS, tractus solitarius. Scale bar = 250 μm.

Figure 4.. Representative sympathetic baroreflexes from urethane-anesthetized, 15-wk-old female rats. Changes in splanchnic sympathetic nerve activity (SNA) were produced by raising mean arterial pressure (AP) with phenylephrine (PE) and decreasing mean AP with sodium nitroprusside and analyzed using the Boltzman equation. A: sigmoid curve from one female lean Zucker rat (F-LZR) with 253 points of data. B: sigmoid curve from one female obese Zucker rat (F-OZR) with 237 points of data. The vertical dotted line denotes the mean AP at the midpoint of the curve (MAP50). C: representative tracings from a female OZR showing a PE-induced rise in AP and baroreflex-mediated inhibition of SNA. Expanded time scale from rat (C) shows baseline SNA (D), and the PE-induced nadir of SNA (E). Group baseline data are in Table 2, and group baroreflex data are in Table 3.

Figure 5.. Physiological responses to activation and inhibition of neurons in the nucleus tractus solitarius (NTS) in urethane-anesthetized female and male obese Zucker rats (OZRs) and lean Zucker rats (LZRs). Individual data points are shown with a red horizontal line representing the mean and capped vertical lines representing the SE. A: nanoinjections of glutamate (1 nmol/50 nL/side with responses averaged) evoked comparable decreases in sympathetic nerve activity (SNA) and mean arterial pressure (MAP) in female OZRs and LZRs (n = 5/group). B: glutamate evoked smaller decreases in SNA and MAP in male OZRs compared with male LZRs (n = 6/group). C: bilateral nanoinjections of GABAA agonist muscimol (100 pmol/100 nL/side) into the NTS produced comparable decreases in SNA in the same female OZRs and LZRs. D: muscimol produced smaller rises in SNA and MAP in the same male OZRs compared with male LZRs. Males and females were analyzed separately by unpaired t tests for each measure. *P < 0.05, OZRs vs. LZRs of same sex. Representative recordings of physiological responses to muscimol in the NTS are in Fig. 6.

Figure 6.. Representative recordings of physiological responses to inhibition of neurons in the nucleus tractus solitarius (NTS) produced by bilateral nanoinjections of muscimol. A: nanoinjections of muscimol (2 downward arrows, left then right side) evoked rises in arterial pressure (AP), sympathetic nerve activity (SNA), and heart rate (HR) in a urethane-anesthetized male lean Zucker rat (LZR). To verify effective inhibition of the NTS, intravenous injections of phenylephrine (PE) (5 µg/kg in 50 µL, at downward arrow) and phenyl biguanide (PBG, 2 µg/kg in 50 µL, at downward arrow) were performed before and after nanoinjections of muscimol into the NTS. B: expanded time scale to show PE-induced rise in AP and baroreflex-mediated decrease in SNA and HR before muscimol and the absence of PE-induced baroreflex-mediated changes in SNA and HR after muscimol. C: expanded time scale to show PBG-induced decreases in AP, SNA, and HR before muscimol and the absence of PBG-induced changes in AP, SNA, and HR after muscimol. Group data for muscimol-induced changes in AP, SNA, and HR are in Fig. 5.

Figure 7.. Hourly average blood glucose measurements by telemetry in conscious rats with access to food at two age ranges. Data are means ± SE. Left panels compare female lean Zucker rats (F-LZRs) and female obese Zucker rats (F-OZRs), and right panels compare the same female OZRs with male OZRs (M-OZRs). A: hourly blood glucose over a 24-h period in 12- to 14-wk-old F-OZRs (n = 13) and F-LZRs (n = 13). B: hourly blood glucose over a 24-h period in 15- to 17-wk-old F-LZRs and F-OZRs from A without one of the OZRs (n = 12). C: hourly blood glucose over a 24-h period in 12- to 14-wk-old F-OZRs from A (n = 13) and M-OZRs (n = 12). D: hourly blood glucose over a 24-h period in 15- to 17-wk-old F-OZRs from B (n = 12) and in six of the male OZRs from C. Hourly values are the mean of twelve 5-min samples occurring 30 min preceding the hour to 30 min after the hour. Data were analyzed for each age range using a two-way ANOVA with repeated measures for time and Tukey’s honestly significant difference (HSD) tests when significant F values were observed. The second factors for rat phenotype (in A and B) or sex (in C and D) were analyzed separately within age range. *P < 0.05, age-matched F-OZRs vs.…

Figure 8.. Glucose tolerance tests in female obese Zucker rats (OZRs) and lean Zucker rats (LZRs) with blood glucose measured by telemetry at three age ranges. Data are presented as means ± SE. The age ranges of rats were 12–13 wk (A), 14–15 wk (B), and 16–17 wk (C). A–C: blood glucose values 60 min before and 180 min after injection of glucose (time 0) measured by telemetry in 5-min increments at three age ranges. Each age range was analyzed by two-way ANOVA with repeated measures followed by Tukey honestly significant difference (HSD) tests when a significant F value was obtained for rat phenotype. There was no significant effect for phenotype in (A) F = 2.27, P = 0.16. There was a significant effect for phenotype in (B) F = 29.82, P < 0.001 and (C) F = 37.72, P < 0.001. *P < 0.05, F-OZRs vs. F-LZRs at those time points. All groups had a significant main effect for time. See Table 5 for group sizes and analyses of single value comparisons during the glucose tolerance tests at each age range.

Figure 9.. Baseline mean arterial pressure (AP) and baroreflex-mediated bradycardia in conscious 24- to 27-wk-old female lean Zucker rats (F-LZRs) (n = 9) and obese Zucker rats (F-OZRs) (n = 6). Values are means ± SE. A: baseline mean AP immediately preceding the infusion of phenylephrine (PE). B: representative recordings of AP, mean AP (MAP), and heart rate (HR) from a female OZR with infusion of PE. C: maximum PE-induced decreases in HR in the first 5 min of the rise in AP in rats from A. D: counts of c-Fos+ neurons in the nucleus tractus solitarius (NTS) at four rostro-caudal levels from bregma. This graph contains three additional rats (n = 11 F-LZRs and 7 F-OZRs) that are not included in (A) due to unstable HR at the beginning of the infusion of PE. E: total counts of c-Fos+ neurons from the four rostro-caudal levels in D. Data in A, C, and E were analyzed by unpaired t tests. *P <0.05, F-OZRs vs. F-LZRs. Data in D were analyzed by two-way ANOVA with repeated measures for bregma level. There was a significant main effect for bregma level (F = 9.645, P < 0.001), consistent with the expected distribution of barosensitive NTS neurons. There was no significant main effect for phenotype (F…