Reactive oxygen species participate in acute renal vasoconstrictor responses induced by ET_Aand ET_Breceptors

Abstract

Just A, Whitten CL, Arendshorst WJ. Reactive oxygen species participate in acute renal vasoconstrictor responses induced by ETA and ETB receptors. Am J Physiol Renal Physiol 294: F719-F728, 2008. First published February 6, 2008 doi:10.1152/ajprenal.00506.2007.-Reactive oxygen species (ROS) play important roles in renal vasoconstrictor responses to acute and chronic stimulation by angiotensin II and norepinephrine, as well as in long-term effects of endothelin-1 (ET-1).Little is known about participation of ROS in acute vasoconstriction produced by ET-1. We tested the influence of NAD(P)H oxidase inhibition by apocynin [4 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 , infused into the renal artery (ira)] on ETA and ET B receptor signaling in the renal microcirculation. Both receptors were stimulated by ET-1, ETA receptors by ET-1 during ET B antagonist BQ-788, and ETB by ETB agonist sarafotoxin 6C. ET-1 (1.5 pmol injected ira) reduced renal blood flow (RBF) 17 Ϯ 4%. Apocynin raised baseline RBF (ϩ10 Ϯ 1%, P Ͻ 0.001) and attenuated the ET-1 response to 10 Ϯ 2%, i.e., 35 Ϯ 9% inhibition (P Ͻ 0.05). Apocynin reduced ETA-induced vasoconstriction by 42 Ϯ 12% (P Ͻ 0.05) and that of ETB stimulation by 50 Ϯ 8% (P Ͻ 0.001). During nitric oxide (NO) synthase inhibition (N -nitro-L-arginine methyl ester), apocynin blunted ETA-mediated vasoconstriction by 60 Ϯ 8% (P Ͻ 0.01), whereas its effect on the ET B response (by 87 Ϯ 8%, P Ͻ 0.001) was even larger without than with NO present (P Ͻ 0.05). The cell-permeable superoxide dismutase mimetic tempol (5 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 ira), which reduces O 2 Ϫ and may elevate H2O2, attenuated ET-1 responses similar to apocynin (by 38 Ϯ 6%, P Ͻ 0.01). We conclude that ROS, O 2 Ϫ rather than H2O2, contribute substantially to acute renal vasoconstriction elicited by both ETA and ETB receptors and to basal renal vasomotor tone in vivo. This physiological constrictor action of ROS does not depend on scavenging of NO. In contrast, scavenging of O 2 Ϫ by NO seems to be more important during ETB stimulation. renal hemodynamics; vascular smooth muscle; renal vascular resistance; afferent arteriole; oxidative stress; redox signaling; nitric oxide; nitric oxide synthase; superoxide dismutase; endothelin REACTIVE OXYGEN SPECIES (ROS) of vascular origin contribute importantly to peripheral vascular resistance and arterial pressure under pathophysiological conditions such as hypertension (34), ischemia (20), diabetes mellitus, and obesity (21). Popular models of established hypertension include those induced chronically (e.g., 1-6 wk) by mineralocorticoid (2, 3, 30, 36, 37), ANG II (33), ET-1 (53), or a high-sodium diet (12, 57).Published in vitro studies of oxidative stress on vascular cells and vessels are also characterized by relatively long-term treatment (e.g., 1-24 h) (10,11,33,36,37,39,53,59).Recent findings indicate that ROS participate in physiological signaling of rapid vascular responses occurring within sec to min. In particular, superoxide (O 2 Ϫ ) mediates a significant portion of the acute vasoconstriction eli...

Modulation of the myogenic mechanism: concordant effects of NO synthesis inhibition and O2− dismutation on renal autoregulation in the time and frequency domains

“…In addition to eliciting vasodilation, NO blunts vasoconstriction produced by G protein-coupled agonists, such as ANG II, endothelin-1, and the catecholamines norepinephrine or phenylephrine (9,38,40). Exaggerated vasoconstriction by one of these agonists might explain the enhanced myogenic response during NOS inhibition.…”

“…Animal studies have demonstrated that O 2 Ϫ dismutation by tempol attenuates renal vasoconstriction induced by ANG II, AVP, endothelin, and norepinephrine, and that this vasoconstrictor action of O 2 Ϫ may involve quenching of NO and also an action independent of NO (39,40,65). On the other hand, our laboratory (65) has shown previously that O 2 Ϫ enhances the renal vasoconstrictor action of AVP primarily by limiting the bioavailability of NO, suggesting different roles as a function of stimulus.…”

Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs

“…These radicals increase the vascular tone, either through direct modulation of vasoconstrictive pathways or inactivation of NO, providing another possible mechanism of Hb-induced vasoactivity (43)(44)(45). Hb-derived free radicals can potentially activate platelets, and markers of platelet activation were indeed found to be increased in patients with sickle-cell disease (46,47).…”

Adenosine A1-receptor deficiency diminishes afferent arteriolar and blood pressure responses during nitric oxide inhibition and angiotensin II treatment

“…In A 1 ϩ/ϩ mice, elevated adenosine levels may enhance arteriolar contraction, but in A 1 -deficient mice this would only activate A 2 -receptors, and thus attenuate the contractile response to ANG II. Moreover, NO produced in the juxtaglomerular apparatus may attenuate the contractile responses via direct actions on vascular muscle cells (7,10) or indirectly via scavenging of ROS (25,30).…”