Hickey 2009 Am J Physiol Cell Physiol

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Hickey AJ, Chai CC, Choong SY, de Freitas Costa S, Skea GL, Phillips AR, Cooper GJ (2009) Impaired ATP turnover and ADP supply depress cardiac mitochondrial respiration and elevate superoxide in nonfailing spontaneously hypertensive rat hearts. Am J Physiol Cell Physiol 297:C766–74.

» PMID:19553568 Open Access

Hickey AJ, Chai CC, Choong SY, de Freitas Costa S, Skea GL, Phillips AR, Cooper GJ (2009) Am J Physiol Cell Physiol

Abstract: Although most attention has been focused on mitochondrial ATP production and transfer in failing hearts, less has been focused on the nonfailing hypertensive heart. Here, energetic complications are less obvious, yet they may provide insight into disease ontogeny. We studied hearts from 12-mo-old spontaneously hypertensive rats (SHR) relative to normotensive Wistar-Kyoto (WKY) rats. The ex vivo working-heart model of SHR showed reduced compliance and impaired responses to increasing preloads. High-resolution respirometry showed higher state 3 (with excess ADP) respiration in SHR left ventricle fibers with complex I substrates and maximal uncoupled respiration with complex I + complex II substrates. Respiration with ATP was depressed 15% in SHR fibers relative to WKY fibers, suggesting impaired ATP hydrolysis. This finding was consistent with a 50% depression of actomyosin ATPase activities. Superoxide production from SHR fibers was similar to that from WKY fibers respiring with ADP; however, it was increased by 15% with ATP. In addition, the apparent Km for ADP was 54% higher for SHR fibers, and assays conducted after ex vivo work showed a 28% depression of complex I in SHR, but not WKY, fibers. Transmission electron microscopy showed similar mitochondrial volumes but a decrease in the number of cristae in SHR mitochondria. Tissue lipid peroxidation was also 15% greater in SHR left ventricle. Overall, these data suggest that although cardiac mitochondria from nonfailing SHR hearts function marginally better than those from WKY hearts, they show dysfunction after intense work. Impaired ATP turnover in hard-working SHR hearts may starve cardiac mitochondria of ADP and elevate superoxide.

Keywords: Adenylate control, Saponin-permeabilized fibers, Hypertensive heart, Oxidative stress, Complex I dysfunction, Respiration

O2k-Network Lab: NZ Auckland Hickey AJ


Labels: Pathology: Cardiovascular 

Organism: Rat  Tissue;cell: Heart  Preparation: Permeabilized tissue 



HRR: Oxygraph-2k 


Correction

An Oroboros O2k was used in this publication, whereas the Anton Paar/Oroboros Oxygraph was the first-generation instrument for high-resolution respirometry, which was replaced by the Oxygraph-2k in 2002.