The Effects of 4-Pentenoic and Pentanoic Acids on the Hypoxic Rat Atria

Abstract

When exposed to hypoxia, the isolated rat atria released lactate into the bathing medium and underwent a rise in resting tension and a decline of the contractions frequency. In some of them, it also occurred a complete cessation of the pacemaker activity. Atria from 24-h fasted rats, when compared to those from fed ones, exhibited a lower lactate output, a higher rise in resting tension, a faster decay of the contraction frequency and an increased occurrence of atrial arrest. In both the fed and fasted rats atria, some triacylglycerol lipolysis remained throughout the hypoxic incubation. Addition of 2 mM 4-pentenoic acid abolished the lipolytic activity and reduced lactate output in both groups of atria. In the fed rats atria it also accelerated the decrease of the pacemaker frequency. Pentanoic acid reduced lactate output in both groups of atria and in those from fed rats it did not alter lipolysis but increased the rise in resting tension, the decline of the pacemaker frequency and the occurrence of atrial arrest. Present data indicate that although 4-pentenoic acid inhibits fatty acid oxidation and endogenous lipolysis, it was not able to reduce the noxious effects of hypoxia. Since the effects of 4-pentenoic acid were rather similar to those of fasting and pentanoic acid, they might be ascribed to the accumulation of its own oxidative metabolites which could be detrimental for the hypoxic atria.

Effects of 5-hydroxydecanoate and ischemic preconditioning on the ischemic-reperfused heart of fed and fasted rats

“…These findings appear rather similar to recent observations concerning 5-HD metabolism which besides its inhibitory effect on the K-ATPmito is a substrate for enzymes of the 13-oxidative pathway (8). Taken together, these evidences suggest that the inhibitory effect of 5-HD on lactate production might be ascribed to a slowed glycolytic rate through the inhibition 6-phosphofructokinase due to an increase of citrate (9) or to the accumulation of its own oxidative metabolites (25). On the other hand, these metabolic effects of 5-HD do not seem to be the consequence of the blockade of K-ATPmito since it has been previously found that diazoxide exerted an inhibitory effect on lactate production (10).…”

“…Therefore, the lowered lactate production observed in hearts treated with 5-HD can not be ascribed to an inhibition of glycogenolysis but seems to be the consequence of the inhibition of glycolytic flux. Regarding this finding it is worthwhile to mention that exogenous short-and medium-chain fatty acids have been previously reported to inhibit glycolytic flux during oxygen limited conditions (13,25). Furthermore, 4-pentenoic acid, which inhibits fatty acid oxidation but can also be q through a different pathway to that involved in its inhibitory properties (2,24), reduces lactate production (25).…”

“…Regarding this finding it is worthwhile to mention that exogenous short-and medium-chain fatty acids have been previously reported to inhibit glycolytic flux during oxygen limited conditions (13,25). Furthermore, 4-pentenoic acid, which inhibits fatty acid oxidation but can also be q through a different pathway to that involved in its inhibitory properties (2,24), reduces lactate production (25). These findings appear rather similar to recent observations concerning 5-HD metabolism which besides its inhibitory effect on the K-ATPmito is a substrate for enzymes of the 13-oxidative pathway (8).…”

Retina stem cells, hopes and obstacles

“…These traits turn them into ideal sources for recovering the different cell types lost in diverse retina degenerative diseases, thus repairing the retina and restoring vision. The feasibility of reprogramming resident, non-neuronal cell types into neurons in vivo [ 126 ] has led to include them as well among the SC types apt to contribute to neuronal regeneration in the retina.…”