Role of Neurohumoral Systems for Pressure Induced Left Ventricular Hypertrophy in Experimental Supravalvular Aortic Stenosis in Rats

Abstract

We studied the role of the sympathetic nervous system and the renin angiotensin system for pressure induced left ventricular hypertrophy (LVH) in 135 rats with experimental supravalvular aortic stenosis (AS). We induced this condition by a silver clip on the ascending aorta, when body weight (BW) was 90 to 100 g. Sympathectomy by 6-OH-dopamine reduced LV norepinephrine content to less than 5%. The renin-angiotensin system was blocked by quinapril, which reduced serum angiotensin converting enzyme (ACE) activity to less than 5%. Aortic stenosis (LV peak systolic pressure 212 +/- 10 mm Hg) induced significant LVH with an increase of LV weight from 198 +/- 3 (sham) to 266 +/- 6 after 6 weeks and to 303 +/- 13 mg/100 g body weight after 12 weeks. Sympathectomy did not reduce LVH 6 weeks after induction of AS (260 +/- 6 mg/100 g body weight). Angiotensin converting enzyme inhibition initiated immediately after induction of AS did not alter the increase of LV mass after 6 weeks (250 +/- 7 mg/100 g body weight). Removing the silver clip 6 weeks after induction of AS resulted in a 90% regression of LVH after 6 more weeks. When ACE-inhibition was started after 6 weeks--ie, once LVH had developed--and maintained for another 6 weeks, an 80% regression of LVH was observed despite the persistent afterload elevation. Our findings of an afterload independent regression of LVH by ACE-inhibition emphasize an important role of the renin angiotensin system for the maintenance of pressure induced LVH.