Role of superoxide anions in the mediation of endothelium-dependent contractions.

Abstract

We designed experiments to characterize the role of superoxide anions in the mediation of endothelium-dependent contractions in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% Oj-6% CO 2 (37°C, pH 7.4). Radioimmunoassay was used to determine the levels of cyclic GMP and cyclic AMP. Calcium ionophore A23187 (1(T 9 to 1(T 6 mol/L) caused concentration-dependent contractions. The removal of endothelium abolished the effect of A23187. Contractions to A23187 were reversed into relaxations in the presence of superoxide dismutase (150 U/mL) or the prostaglandin H 2 /thromboxane A 2 receptor antagonist SQ29548 (10~6 mol/L). Af G -nitro-Larginine methyl ester (3xlO~4 mol/L) augmented contractions to A23187. In rings with endothelium, A23187 (3 x 1(T 7 mol/L) significantly increased levels of both cyclic AMP and cyclic GMP. Indomethacin (10~5 mol/L) inhibited stimulatory effects of A23187 on cyclic AMP production. In contrast, indomethacin augmented A23187-induced production of cyclic GMP. Selective augmentation of cyclic GMP production by indomethacin appears to be due to protection of nitric oxide or a closely related molecule released following translocation of calcium into endothelial cells. Our findings suggest that (1) an increased concentration of calcium in endothelial cells may activate both cyclooxygenase and the L-arginine/nitric oxide pathway, (2) arachidonic acid metabolism via cyclooxygenase is a source of superoxide anions, and (3) superoxide anions may be responsible for impairment of balance between relaxing and contracting factors leading to contraction of underlying smooth muscle cells. (Hypertension. 1994^3:229-235.)

NADPH Oxidase–Derived Superoxide Augments Endothelin-1–Induced Venoconstriction in Mineralocorticoid Hypertension

“…In addition, O 2 Ϫ might act as a direct venoconstrictor, consistent with previous demonstrations of its vasoconstrictor properties. 21,22 In contrast, baseline O 2 Ϫ levels in sham rats were apparently too low to be scavenged by tempol, which did not shift the ET-1-induced venoconstriction curve rightward in vessels from sham rats. The rationale of using ET-1 at a concentration of 10 Ϫ9 mol/L to stimulate O 2 Ϫ was based on our experimental observations that venous O 2 Ϫ levels produced by 10 Ϫ9 mol/L ET-1 in normal rats have already exceeded those found in DOCA-salt rats.…”

“…It has been reported that increased arterial O 2 Ϫ contributes to vasoconstriction by inactivating NO in both animals and humans with cardiovascular diseases, including hypertension. [1][2][3][21][22][23] Arterial O 2 Ϫ levels are markedly increased in DOCA-salt hypertension, a model with low plasma renin but high arterial ET-1 levels. 9 -14 However, it was not clear whether ET-1 also elevates venous O 2 Ϫ levels in this model.…”

Isolated Human and Rat Cerebral Arteries Constrict to Increases in Flow: Role of 20-HETE and TP Receptors

“…These findings could be because of multiple sources of ROS and COXs are present in the cerebral vessels and in the surrounding neural tissues and astrocytes , releasing both constrictor and dilator factors (Cosentino et al, 1994;Wei et al, 1996). Thus, in vivo administration of drugs generating or inhibiting ROS production could activate several opposing vasomotor mechanisms.…”

Working under pressure: the vascular endothelium in arterial hypertension

“…26,64 In addition, O − 2 can act as a vasoconstrictor. [65][66][67][68] Nicotinamide adenine dinucleotide (NADH) dehydrogenase, a mitochondrial enzyme of the respiratory chain, seems to be a major source of O − 2 .…”