Relaxation by urocortin of rat renal arteries: effects of diabetes in males and females

Sanz, Elena; Fernández, Núria; Monge, Luis; Climent, Belén; Diéguez, Godofredo; Garcı́a-Villalón, Ángel Luis

doi:10.1016/s0008-6363(03)00293-1

Cited by 16 publications

(19 citation statements)

References 26 publications

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“…Indeed, urocortin-induced hyperpolarization and relaxation were markedly attenuated by the presence of charybdotoxin, a selective blocker of large conductance Ca 2+ -activated K + channels. Our findings in mesenteric arteries support previous studies carried out in rat basilar arteries (Schilling et al 1998), human saphenous veins (Sanz et al 2002) and rat renal arteries (Sanz et al 2003), in which vasorelaxations induced by urocortin were affected by blockade of Ca 2+ -activated K + channels.…”

Section: Discussionsupporting

confidence: 91%

“…Indeed, in this study urocortin-induced hyperpolarization and relaxation were not affected by the presence of N G -nitro-L-arginine (nitro-Larginine), which inhibits NOS activity. Similar findings were also observed by the others, who reported that urocortin-induced relaxation was not affected by the inhibition of NOS in the coronary arteries (Terui et al 2001), human saphenous veins (Sanz et al 2002), in male rat renal arteries (Sanz et al 2003), and in the rat pulmonary arteries (Chan et al 2004). Furthermore, in this study vasodilatory response to urocortin was not affected in the presence of ODQ, which is an inhibitor of soluble guanylate cyclase (Tseng et al 2000).…”

Section: Discussionsupporting

confidence: 90%

“…These findings suggest that hyperpolarization and relaxation produced by urocortin was not mediated by NO. In contrast, inhibition of NOS partly reduced the relaxation induced by urocortin in the pregnant rat uterine artery (Jain et al 1999), in the rat coronary artery (Huang et al 2003) and in the female rat renal artery (Sanz et al 2003). Similarly, Chen et al (2005) reported that urocortin-induced relaxation in the human internal mammary artery primarily involves NO, which stimu-lates Ca 2 -activated K + channels via cyclic GMP (Chen et al 2005).…”

Section: Discussionmentioning

confidence: 99%

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Urocortin Induces Endothelium-Dependent Vasodilatation and Hyperpolarization of Rat Mesenteric Arteries by Activating Ca2+-Activated K+ Channels

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Özü

Emre

et al. 2007

Tohoku J. Exp. Med.

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Urocortin, a member of corticotropin releasing factor (CRF) peptide family, has positive chronotrophic and inotropic effects on heart and also shows a vasodilatory effect. However, the mechanism underlying its vasodilatory effect has yet to be elucidated. Endotheliumdependent relaxation of resistance arteries is mainly achieved by activation of K + channels. Therefore, we investigated possible role of K + channels and hyperpolarization for the vasodilatory effect of urocortin using the isolated perfused rat mesenteric arteries. Urocortin (0.2 nM) produced a slow-onset decrease in the perfusion pressure of the mesenteric vascular bed, which was elevated by an α 1-adrenoceptor agonist, phenylephrine (2-4 μ M). Urocortin also hyperpolarized the main mesenteric artery. Removal of endothelium with saponin treatment considerably inhibited the relaxation and hyperpolarization induced by urocortin. In contrast, the hyperpolarization was not significantly changed by cyclooxygenase inhibitor, indomethacin (1 μ M) and/or nitric oxide synthase inhibitor, N ω -nitro-L-arginine (100 μ M). Urocortin-induced relaxation was not affected by the combination of a guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 μ M), indomethacin and N ω -nitro-L-arginine. However, the relaxation and hyperpolarization were abolished by high extracelluler potassium concentration (40 mM) or by a large conductance Ca 2+ -activated K + channel blocker, charybdotoxin (1 nM). Glibenclamide (1 μ M), an ATPdependent K + channel inhibitor, did not affect the relaxation and hyperpolarization. These results suggest that urocortin causes endothelium-dependent relaxation and hyperpolarization of rat mesenteric arteries, probably through the activation of charybdotoxin sensitive Ca 2+ -activated K + channels. These findings also indicate an essential role of the endothelium for the urocortin-elicited vascular relaxation and hyperpolarization.urocortin; Ca 2+ -activated K + channels; charybdotoxin; mesenteric artery; hyperpolarization

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Urocortin Induces Endothelium-Dependent Vasodilatation and Hyperpolarization of Rat Mesenteric Arteries by Activating Ca2+-Activated K+ Channels

Seçilmiş

Özü

Emre

et al. 2007

Tohoku J. Exp. Med.

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“…The observed Ucn2-induced renal responses, which occurred in the face of prominent reductions in plasma atrial natriuretic peptide/brain natriuretic peptide, are similar to those seen in our earlier work with the peptide in ovine HF, [12][13][14][15] and are likely a consequence of improvements in glomerular filtration (as judged by the increase in CrCl), renal vasodilatation, 28 and attenuation of circulating antinatriuretic/antidiuretic factors (Ang II, aldosterone, and arginine vasopressin). Direct tubular actions of Ucn2 are also plausible given that not only is the CRF 2 receptor present in the proximal tubules of the kidney, 29 but also administration of the peptide is accompanied by increases in urine cAMP (Ucn2's intracellular second messenger).…”

Section: Discussionsupporting

confidence: 80%

Interactions of Enhanced Urocortin 2 and Mineralocorticoid Receptor Antagonism in Experimental Heart Failure

Rademaker

Charles

Nicholls

et al. 2013

Circ: Heart Failure

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Background-Mineralocorticoid receptor antagonists (MRAs) have become established therapy in heart failure (HF).Urocortin 2 (Ucn2) is a novel peptide with potential in the treatment of this disease. The present study investigated the interactions of acute administration of Ucn2 and an MRA in experimental HF. Methods and Results-Ucn2 and an MRA (canrenoic acid [CA]) were infused for 4 hours, both singly and together, in 8 sheeps with pacing-induced HF. Ucn2, when administered as an adjunct to CA, further improved hemodynamic indices relative to that achieved by CA alone, producing additional increases in cardiac output and decreases in left atrial pressure and peripheral resistance but without eliciting a supplementary reduction in arterial pressure. Ucn2 cotreatment reversed CA-induced rises in circulating aldosterone levels, and also significantly reduced plasma renin activity, angiotensin II, and vasopressin concentrations. Although both CA and Ucn2 infusion produced a diuresis and natriuresis, responses with Ucn2 and Ucn+CA were 2-to 3-fold greater than that elicited by separate CA. Ucn2 cotherapy additionally increased urine potassium and creatinine excretion. In contrast to the rise in plasma potassium induced by CA, Ucn2 cotreatment reduced potassium concentrations. Conclusions-Ucn2 cotreatment with an MRA in HF further improved hemodynamics relative to that achieved by CA alone, while also reducing plasma renin activity, angiotensin II, aldosterone and vasopressin levels, and enhancing renal function. Importantly, Ucn2 prevented CA-induced rises in plasma potassium. These data demonstrate a favorable profile of effects with short-term adjunct Ucn2 therapy and an MRA in HF. (Circ Heart Fail. 2013;6:825-832.)

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“…However, cAMP is a second messenger utilized by many systems activated in HF, and the failure of levels to rise in the Ucn1-treated animals likely reflects the less severe disease status achieved in this group (25). Nevertheless, cAMP was raised sufficiently at the level of cell signaling to induce the significant effects observed with Ucn1 administration, or, alternatively, other pathways may be involved (22,37,42).…”

Section: Discussionmentioning

confidence: 97%

Urocortin 1 administration from onset of rapid left ventricular pacing represses progression to overt heart failure

Rademaker

Charles²,

Richards³

2007

American Journal of Physiology-Heart and Circulatory Physiology

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Rademaker MT, Charles CJ, Richards AM. Urocortin 1 administration from onset of rapid left ventricular pacing represses progression to overt heart failure. Am J Physiol Heart Circ Physiol 293: H1536-H1544, 2007. First published May 25, 2007; doi:10.1152/ajpheart.00377.2007.-Urocortin 1 (Ucn1) may be involved in the pathophysiology of heart failure (HF), but the impact of Ucn1 administration on progression of the disease is unknown. The aim of this study was to investigate the effects of Ucn1 in sheep from the onset of cardiac overload and during the subsequent development of HF. Eight sheep underwent two 4-day periods of HF induction by rapid left ventricular pacing (225 beats/min) in conjunction with continuous infusions of Ucn1 (0.1 g ⅐ kg Ϫ1 ⅐ h Ϫ1 iv) and a vehicle control (0.9% saline). Compared with control, Ucn1 attenuated the pacing-induced decline in cardiac output (2.43 Ϯ 0.46 vs. 3.70 Ϯ 0.89 l/min on day 4, P Ͻ 0.01) and increases in left atrial pressure (24.9 Ϯ 1.0 vs. 11.9 Ϯ 1.1 mmHg, P Ͻ 0.001) and peripheral resistance (38.7 Ϯ 9.4 vs. 25.2 Ϯ 6.1 mmHg ⅐ l Ϫ1 ⅐ min, P Ͻ 0.001). Ucn1 wholly prevented increases in plasma renin activity (4.02 Ϯ 1.17 vs. 0.87 Ϯ 0.1 nmol ⅐ l Ϫ1 ⅐ h Ϫ1 , P Ͻ 0.001), aldosterone (1,313 Ϯ 324 vs. 413 Ϯ 174 pmol/l, P Ͻ 0.001), endothelin-1 (3.8 Ϯ 0.5 vs. 2.0 Ϯ 0.1 pmol/l, P Ͻ 0.001), and vasopressin (10.8 Ϯ 4.1 vs. 1.8 Ϯ 0.2 pmol/l, P Ͻ 0.05) during pacing alone and blunted the progressive increases in plasma epinephrine (2,132 Ϯ 697 vs. 1,250 Ϯ 264 pmol/l, P Ͻ 0.05), norepinephrine (3.61 Ϯ 0.73 vs. 2.07 Ϯ 0.52 nmol/l, P Ͻ 0.05), and atrial (P Ͻ 0.05) and brain (P Ͻ 0.01) natriuretic peptide levels. Ucn1 administration also maintained urine sodium excretion (0.75 Ϯ 0.34 vs. 1.59 Ϯ 0.50 mmol/h on day 4, P Ͻ 0.05) and suppressed pacing-induced declines in creatinine clearance (P Ͻ 0.05). These findings indicate that Ucn1 treatment from the onset of cardiac overload has the ability to repress the ensuing hemodynamic and renal deterioration and concomitant adverse neurohumoral activation, thereby delaying the development of overt HF. These data strongly support a use for Ucn1 as a therapeutic option early in the course of the disease. cardiac output; hormones; renal function UROCORTIN 1 (Ucn1), a 40-amino acid peptide belonging to the corticotropin-releasing factor family (43), is reported to participate in regulation of the cardiovascular system. The peptide is present in high concentrations in the heart (24) and endothelial and smooth muscle cells of the systemic vasculature (12, 17), and its peripheral distribution closely matches that of the corticotropin-releasing factor receptor type 2, the G proteincoupled receptor reported to mediate its cardiovascular bioactivity (22,44). Systemic administration of Ucn1 induces sustained arterial (6,22,44) and venous (38) dilatation, increases in coronary blood flow and conductance, and positive inotropic and chronotropic effects (1,27,32,33,42). Ucn1 has also been shown to prevent cell death in cultured cardiac myocytes exposed to hyp...

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Relaxation by urocortin of rat renal arteries: effects of diabetes in males and females

Abstract: These results suggest that urocortin produces a marked vasodilation of renal arteries, which may be mediated by nitric oxide in females and by activation of potassium channels in both genders, and is reduced by diabetes in renal arteries from females.

Cited by 16 publications

References 26 publications

Urocortin Induces Endothelium-Dependent Vasodilatation and Hyperpolarization of Rat Mesenteric Arteries by Activating Ca2+-Activated K+ Channels

Urocortin Induces Endothelium-Dependent Vasodilatation and Hyperpolarization of Rat Mesenteric Arteries by Activating Ca2+-Activated K+ Channels

Interactions of Enhanced Urocortin 2 and Mineralocorticoid Receptor Antagonism in Experimental Heart Failure

Urocortin 1 administration from onset of rapid left ventricular pacing represses progression to overt heart failure

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