NO Synthase but not NO, HNO or H2O2 Mediates Endothelium-Dependent
Relaxation of Resistance Arteries from Patients with Resistant
Cardiovascular Disease
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 H2O2 although NOS and sGC can be
involved. These vasodilator responses proceed during excessive oxidative
stress.