Chronic Femoral Artery Ligation Increases Skeletal Muscle Interstitial Prostaglandin E2 in the Rat: Implications for the Exercise Pressor Reflex

Abstract

The stimulation of primarily mechanically‐sensitive group III and primarily metabolically‐sensitive group IV muscle afferents during skeletal muscle contraction evokes reflex increases in blood pressure (i.e., the exercise pressor reflex). The exercise pressor reflex is exaggerated in many forms of cardiovascular disease when compared to the reflex found in healthy counterparts. In rats in which a femoral artery is ligated for 72 hours (a model of simulated peripheral artery disease), the mechanically‐sensitive component of the reflex (i.e., the mechanoreflex) contributes importantly to the overall exercise pressor reflex exaggeration. Using a dynamic hindlimb muscle stretch protocol to study the mechanoreflex, we found recently that the increase in blood pressure was greater during stretch of a ligated versus a freely perfused hindlimb. This suggested that a chronic sensitization of mechanically‐activated channels contributed to the exaggerated mechanoreflex in ligated hindlimbs. The identity of the sensitizing chemical, however, was unknown. Experimental evidence has established that cyclooxygenase (COX) products, especially prostaglandins, sensitize mechanically‐activated channels. Accordingly, the purpose of this investigation was to determine whether 72 hour femoral artery ligation increased resting skeletal muscle interstitial prostaglandin E2 (PGE2) concentration in decerebrate, unanesthetized rats. The microdialysis technique was used to collect hindlimb skeletal muscle interstitial fluid in eight rats with a previously ligated femoral artery and a freely perfused femoral artery. We found that resting PGE2 concentration was greater in the ligated (224±44 pg/ml) versus the freely perfused (180±33 pg/ml, p<0.01) hindlimb. To investigate the potential underlying mechanisms of the PGE2 elevation, we quantified both COX expression and COX activity in the soleus muscles (highly oxidative) and white portion of the gastrocnemius muscles (highly glycolytic). Western blot analyses revealed that femoral artery ligation had no effect on COX‐1 or COX‐2 protein expression in the soleus or white gastrocnemius muscles (p‐value range: 0.44 to 0.78). Total COX activity, however, was higher in the white gastrocnemius muscle of ligated hindlimbs compared to freely perfused hindlimbs (p<0.04). There was no difference in total COX activity in the soleus muscle between hindlimbs (p=0.21). We conclude that 72 hours of femoral artery ligation increased resting PGE2 concentration in rat hindlimb skeletal muscles. The higher PGE2 concentration in ligated hindlimb muscles appears attributable to increased COX activity in white, glycolytic muscle portions. Our findings suggest that chronically elevated skeletal muscle interstitial PGE2 concentration may contribute to the exaggerated mechanically‐sensitive component of the exercise pressor reflex found in ligated hindlimb versus a freely perfused hindlimb.Support or Funding Information1R01HL142877 to SWCThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.