Chronic ANG II infusion increases NO generation by rat descending vasa recta

Zhang, Zhong; Rhinehart, Kristie; Solis, Glen; Pittner, J.; Lee-Kwon, Whaseon; Welch, William J.; Wilcox, Christopher S.; Pallone, Thomas L.

doi:10.1152/ajpheart.00623.2004

Cited by 30 publications

(31 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in the present study when NO was reduced in the presence of elevated ANG II, there was not a significant BP-dependent component of juxtamedullary glomerular or outer medullary injury. Previous studies have demonstrated that ANG IIinduced NO production within the kidney attenuates the vasoconstrictor effects of ANG II (9,14,40,47,49). Specifically, our laboratory has demonstrated that ANG II-induced NO production plays a key role in preserving outer medullary blood flow in response to modest doses of ANG II (5 ng · kg Ϫ1 · min Ϫ1 ) (49).…”

Section: Discussionmentioning

confidence: 86%

Renal injury in angiotensin II+l-NAME-induced hypertensive rats is independent of elevated blood pressure

Polichnowski

Lü

Cowley

2011

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Polichnowski AJ, Lu L, Cowley A Jr. Renal injury in angiotensin IIϩL-NAME-induced hypertensive rats is independent of elevated blood pressure. Am J Physiol Renal Physiol 300: F1008-F1016, 2011. First published January 26, 2011 doi:10.1152/ajprenal.00354.2010.-The balance between angiotensin II (ANG II) and nitric oxide plays an important role in renal function and is thought to contribute to the progression of renal injury in experimental hypertension. In the present study, we investigated the extent of blood pressure (BP)-dependent and BP-independent pathways of renal injury following 2 wk of hypertension produced by intravenous infusion of ANG II (5 ng·kg Ϫ1 ·min Ϫ1)ϩN -nitro-L-arginine methyl ester (L-NAME; 1.4 g·kg Ϫ1 · min Ϫ1 ) in male Sprague-Dawley rats. An aortic balloon occluder was positioned between the renal arteries to maintain (24 h/day) BP to the left kidney (servo-controlled) at baseline levels, whereas the right kidney (uncontrolled) was chronically exposed to elevated BP. Over the 14-day experimental protocol, the average BP to uncontrolled kidneys (152.7 Ϯ 1.8 mmHg) was significantly elevated compared with servo-controlled (113.0 Ϯ 0.2 mmHg) kidneys and kidneys from sham rats (108.3 Ϯ 0.1 mmHg). ANG IIϩL-NAME infusion led to renal injury that was focal in nature and mainly confined to the outer medulla. Despite the differences in BP between servo-controlled and uncontrolled kidneys, there was a similar ϳ3.5-fold increase in renal outer medullary tubular injury, ϳ2-fold increase in outer medullary interstitial fibrosis, ϳ2-fold increase in outer medullary macrophage infiltration, and a significant increase in renal oxidative stress, all of which are indicative of BP-independent mediated pathways. The results of this study have important implications regarding the pathogenesis of renal injury in various experimental models of hypertension and provide novel insights regarding the variable association observed between hypertension and renal injury in some human populations. hypertension; angiotensin II; nitric oxide; inflammation; oxidative stress THE PROGRESSION OF RENAL DAMAGE varies widely among hypertensive populations (10,17,36,43) as well as in experimental models of hypertension (2, 29). While elevated blood pressure (BP), per se, clearly plays a dominant role in the progression of renal injury in many forms of hypertension (2,25,29), it is also understood that renal injury continues to worsen in some individuals despite optimal BP control (10,17,45). Several such BP-independent mechanisms have been proposed and are thought to directly contribute to renal injury and/or alter the susceptibility to BP-induced renal injury and broadly include genetic-, dietary-, and neurohumoral-related mechanisms. We have recently reported that elevated circulating levels of ANG II increase the susceptibility to both BP-dependent and BPindependent pathways of tubulointerstitial injury and fibrosis compared with equivalent pressor doses of norepinephrine (NE) (29). A better understanding of the mechanisms tha...

show abstract

Section: Discussionmentioning

confidence: 86%

Renal injury in angiotensin II+l-NAME-induced hypertensive rats is independent of elevated blood pressure

Polichnowski

Lü

Cowley

2011

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…A competitive relationship may exist between NO formation and ROS generation (17). Angiotensin II promotes ROS generation, which can have deleterious effects, particularly when NO is limited (19,35).…”

Section: Discussionmentioning

confidence: 99%

“…NO also inhibits salt reabsorption, thereby reducing oxygen demands within the outer medulla (16). In contrast, angiotensin II constricts DVR (17), enhances sodium reabsorption (18), and favors formation of oxygen-free radicals (19).…”

mentioning

confidence: 99%

Iodixanol, Constriction of Medullary Descending Vasa Recta, and Risk for Contrast Medium–induced Nephropathy

Sendeski¹,

Patzak²,

Pallone³

et al. 2009

Radiology

Self Cite

109

View full text Add to dashboard Cite

Purpose:To determine whether a type of contrast medium (CM), iodixanol, modifies outer medullary descending vasa recta (DVR) vasoreactivity and nitric oxide (NO) production in isolated microperfused DVR. Materials and Methods:Animal handling conformed to the Animal Care Committee Guidelines of all participating institutions. Single specimens of DVR were isolated from rats and perfused with a buffered solution containing iodixanol. A concentration of 23 mg of iodine per milliliter was chosen to mimic that expected to be used in usual examinations in humans. Luminal diameter was determined by using video microscopy, and NO was measured by using fluorescent techniques. Results:Iodixanol led to 52% reduction of DVR luminal diameter, a narrowing that might interfere with passage of erythrocytes in vivo. Vasoconstriction induced by angiotensin II was enhanced by iodixanol. Moreover, iodixanol decreased NO bioavailability by more than 82%. Use of 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (a superoxide dismutase mimetic) prevented both vasoconstriction with iodixanol alone and increased constriction with angiotensin II caused by CM. Conclusion:Iodixanol in doses typically used for coronary interventions constricts DVR, intensifies angiotensin II-induced constriction, and reduces bioavailability of NO. CM-induced nephropathy may be related to these events and scavenging of reactive oxygen species might exert a therapeutic benefit by preventing the adverse effects that a CM has on medullary perfusion. RSNA, 2009 Note: This copy is for your personal, non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, use the Radiology Reprints form at the end of this article. Contrast medium (CM)-induced nephropathy (CIN) is a lifethreatening complication of radiologic examinations and procedures in which an iodinated CM is used (1). In Europe and the United States, CIN accounts for more than 10% of all causes of hospital-acquired acute renal failure (2).Percutaneous coronary angiography is associated with a high risk of CIN in patients with preexisting chronic kidney disease: Roughly onehalf of these patients develop acute renal failure (3) that is associated with a 25% 1-year mortality rate (4). Several prior investigators have studied whether infusing sodium bicarbonate or scavenging reactive oxygen species (ROS) with ascorbic acid or N-acetylcysteine can prevent CIN (5-10). The intrarenal events that underlie CIN remain controversial, and the mechanism by which scavenging ROS might exert a therapeutic benefit remains to be determined.Evidence supports a high degree of vulnerability of the renal outer medulla to CM-induced damage (11). That propensity has been attributed to the nature of tubular-vascular relationships (12). Vulnerability of the thick ascending limbs to ischemic insult therefore may be an inescapable consequence of the anatomic arrangements in the outer medulla. In summary, descending vasa recta (DVR) are microvessels whose luminal diameters approach the d...

show abstract

“…Detection of NO generation by DVR using the DAF2 fluorescent probe is generally feasible but not robust (37,51). We found that detection of NO involves competing effects of DAF2 conversion to its fluorescent form by NO, superimposed on a concomitant leak of DAF2 from the cytoplasm.…”

Section: Discussionmentioning

confidence: 86%

“…To quantify changes in vessel diameter, DVR were mounted on concentric pipettes, microperfused, and recorded by videomicroscopy. As previously described, vessel contraction was quantified by measuring internal diameter at the site of maximal contraction by image analysis (32,51).…”

Section: Isolation Of Dvrmentioning

confidence: 99%

Chronic ouabain treatment induces vasa recta endothelial dysfunction in the rat

Cao¹,

Payne²,

Lee-Kwon³

et al. 2009

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

([Ca 2ϩ ]CYT) signaling. In this study, we examined the expression of the ouabain-sensitive Na-K-ATPase ␣2 subunit in the rat renal vasculature and tested effects of acute ouabain exposure and chronic ouabain treatment on DVR. Immunostaining with antibodies directed against the ␣2 subunit verified its expression in both DVR pericytes and endothelium. Acute application of ouabain (100 or 500 nM) augmented the DVR nitric oxide generation stimulated by acetylcholine (ACh; 10 M). At a concentration of 1 mM, ouabain constricted microperfused DVR, whereas at 100 nM, it was without effect. Acute ouabain (100 nM) did not augment constriction by angiotensin II (0.5 or 10 nM), whereas L-nitroarginine methyl esterinduced contraction of DVR was slightly enhanced. Ouabain-hypertensive (OH) rats were generated by chronic ouabain treatment (30 g ⅐ kg Ϫ1 ⅐ day Ϫ1 , 5 wk). The acute endothelial [Ca 2ϩ ]CYT elevation by ouabain (100 nM) was absent in DVR endothelia of OH rats. The [Ca 2ϩ ]CYT response to 10 nM ACh was also eliminated, whereas the response to 10 M ACh was not. The endothelial [Ca 2ϩ ]CYT response to bradykinin (100 nM) was significantly attenuated. We conclude that endothelial responses may offset the ability of acute ouabain exposure to enhance DVR vasoconstriction. Chronic exposure to ouabain, in vivo, leads to hypertension and DVR endothelial dysfunction, manifested as reduced [Ca 2ϩ ]CYT responses to both ouabain-and endothelium-dependent vasodilators. kidney; medulla; microcirculation; nitric oxide; blood flow "OUABAIN-LIKE FACTORS" (OLF), synthesized by the adrenal gland and hypothalamus, inhibit Na ϩ /K ϩ exchange (19, 46) and activate signaling cascades (6, 7, 44) by binding to Na-KATPase ␣-subunits. In rodents, the ␣1 isoform of Na-KATPase that maintains Na ϩ and K ϩ gradients across cell membranes has very low affinity (K d Ͼ 10 M) for ouabain. In contrast, the ␣2 and ␣3 isoforms have high affinity for ouabain (K d Ͻ 50 nM), but are less abundantly expressed (3, 48). It has been proposed that targeting of the ␣2 isoform to cellular microdomains where ER/SR protrusions abut the plasma membrane (4, 7) may modulate intracellular Na ϩ and reduce Ca 2ϩ extrusion via Na ϩ /Ca 2ϩ exchange to enhance Ca 2ϩ sequestration into ER/SR stores. Evidence favoring that hypothesis has been accumulating. Low-dose (10 -100 nM) ouabain enhances Ca 2ϩ release in smooth muscle and endothelium (2, 35) and increases resting cytoplasmic Ca 2ϩ ([Ca 2ϩ ] CYT ) and myogenic tone (35,48).A role for OLF in hypertension is also well supported. Chronic administration of ouabain into rodents induces hypertension (26, 28), and many patients with essential hypertension have high plasma ouabain levels (43). Transgenic mice in which the ␣2 Na-K-ATPase binding site for ouabain has been mutated are resistant to both ouabain-and ACTH-induced hypertension, supporting a causal role in hypertension for both ouabain and the ␣2 ouabain receptor (12, 13).Detailed mechanisms by which ouabain induces hypertension remain to be elucidated. ...

show abstract

Chronic ANG II infusion increases NO generation by rat descending vasa recta

Cited by 30 publications

References 48 publications

Renal injury in angiotensin II+l-NAME-induced hypertensive rats is independent of elevated blood pressure

Renal injury in angiotensin II+l-NAME-induced hypertensive rats is independent of elevated blood pressure

Iodixanol, Constriction of Medullary Descending Vasa Recta, and Risk for Contrast Medium–induced Nephropathy

Chronic ouabain treatment induces vasa recta endothelial dysfunction in the rat

Contact Info

Product

Resources

About