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Figure 1 illustrates representative recordings of developed force in isolated rings of cat coronary artery with an intact endothelium. The responses on the left are those obtained prior to addition of TNF. It is evident that all endothelium-dependent dilators (eg, ACh, ADP, and the calcium iono-phore A23187) as well as the endothelium-independent dilator (eg, acidified sodium nitrite [NaNOj) relax these coronary artery rings. ACh acts on the endothelium via M2 or M3 muscarinic receptors to release EDRF; ADP also acts through its own specific receptors to release EDRF, but A23187 releases EDRF independendy of endothelial cell receptors. NaN02 at pH 2 actually releases NO, the major form of EDRF, and hence dilates vascular smooth muscle direcdy (ie, without the obligatory role of EDRF). After incubation of the rings in 4 |xg/ml of TNF for 2 h, the vasorelaxation responses to the receptor-mediated, endothelial-dependent dilators were markedly inhibited, but the relaxant responses to A23187 and NaNOz were normal. Figure 2 summarizes the statistical evaluation of the vasorelaxant response to ACh, ADP, A23187, and NaN02 in a large series of cat coronary artery rings. Figure 1. Representative recordings of isolated cat coronary artery rings precontracted with lOnM U-46619 (arrows). Responses to acetylcholine (ACh), lOOpM to lOOnM; adenosine diphosphate (ADP), lOOnM to 100m.M; A23187, InM to l|iM; and acidified sodium nitrite (NaN02, lOOnM to IOOjiM are indicated by the dots. Responses were measured before and after TNF incubation (4^xg/ ml) for 2 h. Figure 2. Summary of responses to lOOnM ACh, 100p.M ADP, 1|&M A23187, and lOOfiM NaNO, before and after incubation for 2 h with 4 M-g/ml TNF. Bar heights are means, brackets indicate ± SEM, numbers below bars are numbers of rings studied.