Autophagy is altered in skeletal and cardiac muscle of spontaneously hypertensive rats

Abstract Aim Autophagy is a subcellular degradation mechanism important for muscle maintenance. Hypertension induces well‐characterized pathological changes to the heart and is associated with impaired function and increased apoptotic signalling in skeletal muscle. We examined whether essential hypertension affects several autophagy markers in skeletal and cardiac muscle. Methods Immunoblotting and q RT ‐ PCR were used to measure autophagy‐related proteins/m RNA in multiple skeletal muscles as well as left ventricle ( LV ) of spontaneously hypertensive rats ( SHR ) and normotensive W istar– K yoto rats ( WKY ). Results Skeletal muscles of hypertensive rats had decreased ( P < 0.01) cross‐sectional area of type I fibres (e.g. soleus WKY : 2952.9 ± 64.4 μm 2 vs. SHR : 2579.9 ± 85.8 μm 2 ) and a fibre redistribution towards a ‘fast’ phenotype. Immunoblot analysis revealed that some SHR skeletal muscles displayed a decreased LC 3 II / I ratio ( P < 0.05), but none showed differences in p62 protein. LC 3 and LAMP 2 m RNA levels were increased approx. 2–3‐fold in all skeletal muscles ( P < 0.05), while cathepsin activity, cathepsin L m RNA and A tg7 protein were increased 16–17% ( P < 0.01), 2–3‐fold ( P < 0.05) and 29–49% ( P < 0.01), respectively, in fast muscles of hypertensive animals. Finally, protein levels of BAG 3, a marker of chaperone‐assisted selective autophagy, were 18–25% lower ( P < 0.05) in SHR skeletal muscles. In the LV of SHR , LC 3 I and p62 protein were elevated 34% ( P < 0.05) and 47% ( P < 0.01), respectively. Furthermore, p62 m RNA was 68% higher ( P < 0.05), while LAMP 2 m RNA was 45% lower ( P < 0.05), in SHR cardiac muscle. There was no difference in B eclin1, A tg7, B nip3 or BAG 3 protein in the LV between strains. Conclusion These results suggest that autophagy is altered in skeletal and cardiac muscle during hypertension.