CARDIAC GLUCOSE AND FATTY-ACID OXIDATION IN THE STREPTOZOTOCIN-INDUCED DIABETIC SPONTANEOUSLY HYPERTENSIVE RAT

Hypertension intensifies the cardiac dysfunction of diabetes. We inves tigated the possible role of altered exogenous fuel oxidation in this phenomenon. Diabetes was induced by streptozotocin in spontaneously hy pertensive rats and normotensive Sprague-Dawley rats. Two weeks later, mechanical performance and the oxidation of glucose and palmitate wer e quantified in working hearts ex vivo at intermediate and high worklo ads. The results showed that the nondiabetic spontaneously hypertensiv e rat hearts, compared with those of the normotensive controls, oxidiz ed glucose at a higher rate but oxidized palmitate at a much lower rat e, as reported previously. The effects of diabetes in the hypertensive rats, compared with its effects in the normotensive strain, were char acterized by (1) a more pronounced decrease in heart performance, (2) either a similar or a less marked reduction in the rate of glucose oxi dation, depending on the workload, and (3) a relatively greater increa se in palmitate oxidation, particularly at the higher workload. These findings suggest that the exaggerated stimulation of fatty acid oxidat ion by diabetes in the hypertrophic left ventricle may be a more impor tant contributor to the premature mechanical dysfunction than the inhi bition of glucose oxidation. Possible mechanisms include antagonism of energetically favorable shifts in fuel oxidation or inhibition of acc elerated membrane lipid biosynthesis in left ventricular hypertrophy.