Abstract
Background and Purpose: Superoxide anions can reduce the
bioavailability and actions of endothelium-derived NO. In human
resistance-sized arteries, endothelium-dependent vasodilatation can be
mediated by H2O2 instead of NO. We
tested the hypotheses that in resistance arteries from patients with
resistant cardiovascular disease (CVD),
endothelium-dependent
vasodilatation uses mechanisms that are either insensitive to oxidative
stress or involve a reactive oxygen species.
Experimental Approach: Small arteries were isolated from
biopsies of the parietal pericardium of patients undergoing elective
cardiothoracic surgery and were studied by immunohistochemical and organ
chamber techniques.
Key Results: NO-synthases 1, 2 and 3, superoxide dismutase 1
and catalase proteins were observed in the microvascular wall. Relaxing
responses to bradykinin were endothelium dependent. During submaximal
depolarization-induced contraction, these relaxations were inhibited by
inhibitors of NO-synthases (NOS) and soluble guanylyl cyclase (sGC) but
not by scavengers of NO or HNO, inhibitors of cyclooxygenases, neuronal
NO-synthase, superoxide dismutase or catalase, or by exogenous catalase.
During contraction stimulated by endothelin-1, these relaxations were
not reduced by any of these interventions except DETCA which caused a
small reduction.
Conclusion and Implications: In resistance arteries from
patients with resistant CVD, endothelium-dependent relaxations seem not
to be mediated by NO, HNO or H2O2although NOS and sGC can be involved. These vasodilator responses
proceed during excessive oxidative stress.
Keywords: Bradykinin, coronary artery disease, endothelin-1,
oxidative stress, superoxide dismutase