Effects of long-term pressure overload on regional myocardial glucose and free fatty acid uptake in rats: A quantitative autoradiographic study

To investigate the effects of long-term pressure overload on regional myocardial substrate use, we performed quantitative autoradiography using 2 -deoxy-D-[U-¹⁴C]glucose (¹⁴C-DG) and β-methyl[1-¹⁴C]heptadecanoic acid (¹⁴C-BMHDA) in conscious rats with a 10-week ascending aortic constriction. Heart weight/body weight ratio increased by 27% in aortic-constricted rats as compared with sham-operated rats (p<0.01). Myocardial ¹⁴C-DG uptake increased (258±63 vs. 144±41 nCi/g, p<0.01, n=6 for each group); however, ¹⁴C-BMHDA extraction decreased (251±69 vs. 342±75 nCi/g, p<0.05, n=7 for each group) in aortic-constricted rats as compared with sham-operated rats. In sham-operated rats, both ¹⁴C-DG and ¹⁴C-BMHDA uptakes were higher in the left ventricular anterior and lateral walls as compared with the posterior wall or the interventricular septum. In aortic-constricted rats, ¹⁴C-DG uptake also increased in the interventricular septum, as well as in the left ventricular anterior and lateral walls, as compared with the posterior wall. There was, however, no regional difference in ¹⁴C-BMHDA extraction among these four regions. Myocardial blood flow distribution determined by 4-[N-methyl-¹⁴C]iodoantipyrine or myocyte width showed no regional variations among the four regions, either in aortic-constricted or sham-operated rats. Regional interstitial fibrosis was small in either group. The present study suggests that myocardial substrate uptake is altered nonhomogeneously, and that the nonhomogeneity is not because of regional variations in blood flow distribution, myocyte hypertrophy, or interstitial fibrosis. The results of angiotensin II-induced acute pressure overloading in other sham-operated rats, in which a remarkable increase in myocardial ¹⁴C-BMHDA extraction (n=3, p < 0.01) and no difference in ¹⁴C-DG uptake (n=3) as compared with normotensive sham-operated rats were elicited, suggest that the findings in aortic-constricted rats are not direct responses to increased left ventricular pressure itself but rather should be explained by still unknown factors related to prolonged pressure overload.