Structural adaptation to ischemia in skeletal muscle: effects of blockers of the renin-angiotensin system

OBJECTIVETo investigate the effects of long-term treatment with blockers of the renin–angiotensin system on capillarization and growth of fibers in ischemic hind-limb muscles and in muscles under normal growth conditions. METHODSIschemia was induced by partial ligation of the left common iliac artery. RESULTSIschemia resulted in a significant increase in capillary and fiber density in the soleus muscle, a significant decrease in mean fiber size and a decrease in muscle cross-sectional area after 4 weeks compared with the contralateral nonischemic muscle. Ischemia also significantly decreased the muscle body weight ratio of the left soleus muscle. We observed no significant effect on total number of capillaries and capillaryfiber ratio, suggesting that ischemia did not result in an increase in capillarization in this muscle. Treatments with subhypotensive and with hypotensive doses of the angiotensin converting enzyme (ACE) inhibitor benazeprilat, the angiotensin (Ang) II AT1 antagonist valsartan, or the Ang II AT antagonist PD 123 319 for 4 weeks did not influence any of the above-described changes in the normal and ischemic muscles and treatment effects were also independent of the degree of reduction of blood pressure. CONCLUSIONTreatments with an ACE inhibitor and with Ang II receptor antagonists in dose ranges that moderately lower blood pressure do not influence vessel density and any of the other structural adaptations after hind-limb ischemia. Administrations of ACE inhibitors and Ang II AT1 antagonists may therefore be adequate and beneficial therapies under ischemic conditions, such as in the treatment of hypertension complicated by intermittent claudication, for which treatment must not increase ischemia.