Figure 9.

Proposed TS Signal Transduction Cascade

ISO injection results in β-adrenoceptor activation, leading to activation of coupled endothelial nitric oxide synthase (eNOS) receptors and to mitochondrial reactive oxygen species release. With increased superoxide (O₂^–) and nitric oxide (NO) production, there is formation of peroxynitrite (ONOO^–), leading to protein nitration, myocardial inflammation, and poly(ADP-ribose) polymerase-1 (PARP-1) activation, resulting in energetic impairment as well as PAR production. Inflammatory activation of glycocalyx shedding contributes to the development of edema and to increased expression of TXNIP. ATP = adenosine triphosphate; BNP = B-type natriuretic peptide; DNA = deoxyribonucleic acid; iNOS = inducible nitric oxide synthase; NAD⁺ = nicotinamide adenine dinucleotide; other abbreviations as in Figure 3.