In human pericardial resistance arteries, effects of the endothelium-dependent vasodilator bradykinin are mediated by NO during contraction induced by K(+) or the TxA2 analogue U46619 and by H2 O2 during contraction by endothelin-1 (ET-1), respectively. We tested the hypotheses that ET-1 reduces relaxing effects of NO and increases those of H2 O2 in resistance artery smooth muscle of patients with cardiovascular disease. Arterial segments, dissected from the parietal pericardium of 39 cardiothoracic surgery patients, were studied by myography during amplitude-matched contractions induced by K(+) , the TXA2 analogue U46619 or ET-1. Effects of the NO-donor Na-nitroprusside (SNP) and of exogenous H2 O2 were recorded in absence and presence of inhibitors of cyclooxygenases, NO-synthases and small and intermediate conductance calcium-activated K(+) channels. During contractions induced by either of the three stimuli, the potency of SNP did not differ and was not modified by the inhibitors. In vessels contracted with ET-1, the potency of H2 O2 was on average and in terms of inter-individual variability considerably larger than in K(+) -contracted vessels. Both differences were not statistically significant in presence of inhibitors of mechanisms of endothelium-dependent vasodilatation. In resistance arteries from patients with cardiovascular disease, ET-1 does not selectively modify smooth muscle relaxing responses to NO or H2 O2 . Furthermore, the candidate endothelium-derived relaxing factor H2 O2 also acts as an endothelium-dependent vasodilator. This article is protected by copyright. All rights reserved.
Basic and Clinical Pharmacology and Toxicology, 2018, Vol 122, Issue 1