Hypertension is an important clinical symptom of metabolic syndrome (MetS). Rats selectively bred for low intrinsic aerobic capacity (LCR) are animal models for MetS, and present with increased blood pressure and vascular dysfunction. In contrast, rats selected for high intrinsic aerobic capacity (HCR) display reduced vascular inflammation and no metabolic abnormalities. Two important enzymes for vascular inflammation and the resolution of inflammation are cyclooxygenase (COX) and lipoxygenase (LOX), respectively; however, it is unknown whether COX and LOX play a role in the vascular function of LCR and HCR. We hypothesized that mesenteric resistance arteries (MRA) from untrained LCR present increased COX activity, while arteries from HCR show decreased COX and increased LOX activity.
Female (18-38 weeks old) LCR, HCR, and high response trained (HRT) rats, control, were used. HRT rats present higher intrinsic aerobic capacity than LCR, but lower than HCR. MRA were mounted onto a wire myograph. One-way ANOVA: p<0.05: *vs. control (HRT); # vs. HCR; & vs. absence of indomethacin (INDO), a COX inhibitor. LCR rats showed increased periovarian fat pad [HRT: 0.95±0.1 (n=7) vs. LCR: 1.80±0.1* # (n=7) vs. HCR: 1.18±0.1 (n=7) (g)]. No significant differences were observed in the KCl (120 mM), acetylcholine, and sodium-nitroprusside-induced responses. However, LCR presented a decrease in phenylephrine (PE)-induced contraction [PE: E max %: HRT: 103±3 (n=8); LCR: 74±9* # (n=11); HCR: 112±5 (n=9)]. Inhibiting COX [INDO, 10 μM] decreased contraction in HRT arteries, but had little effect on HCR arteries. Contrarily, INDO abolished contraction in MRA from LCR [PE+INDO: E max %: HRT: 31±18 & (n=7); LCR: 2±0.9 & (n=8); HCR: 77±9 (n=8)]. Lipoxin (LXA4), a LOX-derived mediator for resolution of inflammation, induced contraction in MRA from HCR, but relaxation in LCR and HRT arteries [LXA4: E max %: HRT: -69±19 (n=4); LCR: -18±9 (n=3); HCR: 11±5 (n=4)*]. Thus, HCR are unresponsive to COX inhibition, suggesting a change from a normal inflammatory state to a higher resolution state. LCR display low-grade chronic inflammation via increased COX activity. These data reveal novel, inherited mechanisms for vascular physiology in high vs. low intrinsic aerobic capacity.
- HYPERTENSION Journal
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