STRUCTURAL ADAPTATION TO ISCHEMIA IN SKELETAL-MUSCLE - EFFECTS OF BLOCKERS OF THE RENIN-ANGIOTENSIN SYSTEM

Objective To investigate the effects of long-term treatment with block ers of the renin-angiotensin system on capillarization and growth of f ibers in ischemic hindlimb muscles and in muscles under normal growth conditions. Methods Ischemia was induced by partial ligation of the le ft common iliac artery. Results Ischemia resulted in a significant inc rease in capillary and fiber density in the soleus muscle, a significa nt decrease in mean fiber size and a decrease in muscle cross-sectiona l area after 4 weeks compared with the contralateral nonischemic muscl e. Ischemia also significantly decreased the muscle : body weight rati o of the left soleus muscle. We observed no significant effect on tota l number of capillaries and capillary : fiber ratio, suggesting that i schemia did not result in an increase in capillarization in this muscl e. Treatments with subhypotensive and with hypotensive doses of the an giotensin converting enzyme (ACE) inhibitor benazeprilat, the angioten sin (Ang) II AT(1) antagonist valsartan, or the Ang II AT(2) antagonis t 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. Conclus ion Treatments with an ACE inhibitor and with Ang II receptor antagoni sts in dose ranges that moderately lower blood pressure do not influen ce vessel density and any of the other structural adaptations after hi nd-limb ischemia. Administrations of ACE inhibitors and Ang II AT(1) a ntagonists may therefore be adequate and beneficial therapies under is chemic conditions, such as in the treatment of hypertension complicate d by intermittent claudication, for which treatment must not increase ischemia.