Sympathoadrenergic suppression improves heart function by upregulating the ratio of sRAGE/RAGE in hypertension with metabolic syndrome

(−20%) and increased sRAGE levels in heart (+80%) and serum (+180%) versus sham-operated SHRob. Myocardial fibrosis correlated inversely with myocardial sRAGE content (r = −0.79; p = .004; n = 10). Myocardial sRAGE shedding active A-Disintegrin-And-Metalloprotease-10 (ADAM-10) was decreased in SHR (−33% versus controls) and in SHRob (−54% versus SHR), and was restored after RDN (+129% versus SHRob). Serum ADAM-10 activity was also decreased in SHRob (−66% versus SHR) and restored after RDN (+150% versus SHRob). In vitro, isoproterenol induced a ß1-adrenergic receptor mediated increase of RAGE expression in splenocytes (+200%) and decreased sRAGE secretion of splenocytes and cardiac fibroblasts (−50% and −49%) by ß2-adrenergic receptor stimulation mediated suppression of ADAM-10 activity. In conclusion, sympathetic activity affects sRAGE/RAGE-balance, which can be suppressed through sympathetic modulation by RDN, preventing RAGE-induced cardiac damage in hypertension with metabolic syndrome.