Role of the fuel utilized by tissues on coronary vessel response to physical stimuli in isolated rat hearts

In isolated rat hearts which can or cannot utilize fatty acids (FA) as substrates the coronary responses to an increase in flow were studied under three different conditions: a) control, during perfusion with glucose-enriched Tyrode solution which allowed the hearts to utilize long-chain FA from the endogenous pool, b) during forced utilization of glucose obtained with oxfenicine, an inhibitor of long-chain FA oxidation, and c) during restored utilization of FA obtained with the addition of hexanoic acid which bypasses the blockade induced by oxfenicine. A step increase in coronary flow (50 %) induced an increase in coronary perfusion pressure whose initial slope (first 60-80 s) was similar in all the conditions of buffer perfusion, thereafter the pressure tended to further increase under control conditions (buffer a), but to decrease during oxfenicine (buffer b). The addition of hexanoic acid to the perfusion solution (buffer c) abolished the effect of oxfenicine. Steady-state conditions were reached after four minutes of increased flow, when perfusion pressure increased by about 70 and 65 % under control conditions and during hexanoate, respectively, but only by 45 % during oxfenicine. In isolated rat hearts during inhibition of FA utilization, an increase in flow elicited a reduced increase in perfusion pressure that resulted in delayed coronary dilation. It follows that the resulting shear stress is substrate-sensitive.