Metabolic syndrome emerges after artificial selection for low baroreflex sensitivity

Abstract

Aims: It is unclear whether the impaired BRS plays a key role in the incidence of cardiovascular diseases. The molecular mechanism of impaired BRS remains to be fully elucidated. We hypothesized that selection of rats based on deficient and normal intrinsic BRS would yield models that reflect cardiovascular diseases risk.

Methods and results: Twenty generations of selection produced arterial baroreflex low rats and normal rats that differed in BRS by about 2.5-fold change. Metabolic syndrome (including hypertension, overweight, hyperlipemia, and hyperglycemia) emerged in ABR-DRs. Although ABR-DRs consumed less food, they gained significantly more body weight.

Conclusion: Our study demonstrated that intrinsic low BRS induced hypertension and metabolic disorder. Restoration of impaired BRS might be a potent target of therapeutic intervention in metabolic syndrome.

Keywords: ABR-DRs; ABR-NRs; baroreflex sensitivity; hypertension; metabolic syndrome.

Figure 1

Twenty generations of selective breeding in rats results in two divergent strains. A, BRS, SBP, DBP, and heart rate for two populations of rats across 20 generations. B, Incidence of hypertension across 20 generations. Chi‐square test was used to compare the group with and without hypertension. C, Representative scatter plots showed the significant and negative relationships between BRS and mean blood pressure (MBP) at generation 20, n = 48. Data are expressed as mean ± s.d. For ABR‐NRs, n = 819 in total; for ABR‐DRs, n = 779 in total. ANOVA for repeated measurement data was used to compare 2 strains of animals at different ages for (A). *P < 0.05,**P < 0.01

Figure 2

BRS (A), heart rate (B), SBP, and DBP (C,D) were measured in different ages of male ABR‐NRs and ABR‐DRs from generation 20 (1, 2, 4, 6, and 8 months, n = 7‐10 in different ages). Data are expressed as mean ± s.d. ANOVA for repeated measurement data was used to compare two strains of animals at different ages. *P < 0.05, **P < 0.01

Figure 3

ABR‐DRs show over weight, impaired glucose, and insulin tolerance. (A) Representative image of ABR‐DRs and ABR‐NRs. (B) Body weight and diet intake for ABR‐NRs and ABR‐DRs at different ages (1‐12 months) of generation 20, n = 20. (C) Glucose tolerance test (GTT), the area under the curve (AUC), and insulin concentration during the GTT (n = 10). (D) Insulin tolerance test (ITT, left), Glucose during ITT presented as the percentages over the baseline level (middle) and the percentage changes of AUC over control (right). n = 9. Data are expressed as mean ± s.d. ANOVA for repeated measurement data was used to compare two groups at different ages for (B) and at different time for (C) and (D). Student's t test was also used for (C) and (D). *P < 0.05,**P < 0.01

Figure 4

ABR‐DRs do not show the sensitivity of cardiac arrhythmia. They have normal sympathetic function and impaired parasympathetic function. (A) The threshold doses of aconitine required for ventricular premature beat (VPB), ventricular fibrillation (VF), and cardiac arrest (CA), n = 6. (B) Baseline of renal sympathetic nerve activity (RSNA). (C) The response of RSNA to blood pressure (BP) elevation. (D) Change of heart rate in response to the BP elevation. For panels (B‐D), n = 5. Data are expressed as mean ± s.d. Student's t test was used. **P < 0.01, n.s., no significance