Endothelin in experimental congestive heart failure in the anesthetized dog

Cavero, Patricia G.; Miller, WL; Heublein, D. M.; Margulies, Kenneth B.; Burnett, John C.

doi:10.1152/ajprenal.1990.259.2.f312

Cited by 58 publications

(38 citation statements)

References 11 publications

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“…Nonetheless, neurohumoral activation is known to take place and play an important role in the progression of ventricular dysfunction (11). Specifically, activation of natriuretic and vasorelaxing factors such as ANP (9) and brain natriuretic peptide (12) may function to oppose the co-activation of local and circulating vasoconstrictive and sodium-retaining factors like norepinephrine, angiotensin II and endothelin (13). The current study is consistent with the concept that ADM which mediates its biological actions via generation of cAMP (14,15) could also play a compensatory role in CHF to enhance myocardial contractility via cAMP.…”

Section: Discussionmentioning

confidence: 99%

Cardiac secretion of adrenomedullin in human heart failure.

Jougasaki

Rodeheffer²,

Redfield³

et al. 1996

J. Clin. Invest.

162

102

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Adrenomedullin (ADM) is a newly discovered endogenous vasorelaxing and natriuretic peptide. Recently, we have reported that plasma ADM is increased in severe congestive heart failure (CHF) in humans and that increased immunohistochemical staining is observed in the failing human ventricular myocardium. The present study was designed to test the hypothesis that the failing human ventricle secretes ADM and that circulating ADM progressively increases with the severity of clinical CHF. Plasma ADM was significantly increased in human CHF (39.8 Ϯ 3.6 pg/ml, P Ͻ 0.001 vs. normal) as compared with normal subjects (14.4 Ϯ 2.7 pg/ml). Plasma ADM was increased in mild CHF (NYHA class II, 30.1 Ϯ 3.4 pg/ml, P Ͻ 0.01 vs. normal), moderate CHF (NYHA class III, 31.5 Ϯ 3.0 pg/ml, P Ͻ 0.01 vs. normal), and severe CHF (NYHA class IV, 66.1 Ϯ 9.4 pg/ml, P Ͻ 0.001 vs. normal). In 13 patients with CHF in whom plasma samples were obtained from aorta (AO), coronary sinus (CS) and anterior interventricular vein (AIV), there was a significant step-up in plasma ADM between AO and AIV (50.6 Ϯ 9.3 pg/ml and 62.1 Ϯ 11.1 pg/ml, respectively, P Ͻ 0.01) and between AO and CS (50.6 Ϯ 9.3 pg/ml and 58.6 Ϯ 11.4 pg/ml, respectively, P Ͻ 0.05). The current study demonstrates that the failing human heart secretes ADM in human CHF suggesting contribution to the increase in plasma ADM, and indicates for the first time an additional endocrine system of cardiac origin which is activated in human CHF and may function in cardiorenal regulation. ( J. Clin. Invest. 1996. 97: 2370-2376.)

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Section: Discussionmentioning

confidence: 99%

Cardiac secretion of adrenomedullin in human heart failure.

Jougasaki

Rodeheffer²,

Redfield³

et al. 1996

J. Clin. Invest.

162

102

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“…Some investigators 12 found that ET-1 increased plasma renin activity, but others reported that a relatively low dose of ET-1 significantly reduced it. 13 Such discrepant effects on the renin-angiotension system are probably due to the complexity of the nature of controlling renin release in vivo. It is most likely that the several control mechanisms known to play important roles in the regulation of renin release are affected by administration of ET-1, such as the macula densamediated pathway, the intrarenal baroreceptor, and possibly a direct effect of ET-1 on the juxtaglomerular cells.…”

Section: Effect Of Endothelin-1 On Glomerular Hydraulic Pressure and mentioning

confidence: 99%

Effect of endothelin-1 on glomerular hydraulic pressure and renin release in dogs.

et al. 1993

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The present study was designed to analyze quantitatively the effects of a wide range of endothelin-1 levels on renal hemodynamlcs and renin release in the canine nonftltering kidney, including their effects on glomerular hydraulic pressure. Intrarenal infusion of endothelin-1 produced dose-dependent reductions in renal blood flow, but it did not affect glomerular hydraulic pressure until the infused dose reached high rates. At the rate of 1.0 ng/kg per minute, endothelin-1 reduced renal blood flow by 23% (><0.01), whereas glomerular hydraulic pressure was not significantly changed from 68.1 ±1.3 to 67.4 ± 1.2 mm Hg. However, with a higher rate of endothelin-1 infusion (5.0 and 10.0 ng/kg per minute), glomerular hydraulic pressure fell to 59.5±1.3 and 5L5±1.8 mm Hg (p<0.01), whereas renal blood flow was reduced from 154.5±15 to 83.0±9.5 and 53.5±9.9 mL/min, respectively. Endothelin-1 infusion also produced an inhibitory effect on renin release. With infusion at 1.0 ng/kg per minute, renin release fell from the control level of 47.9±5.6 to 26.6±4.9 units/min per gram kidney weight (p<0.01), and it fell further to 16.1 ±4.3 units/min per gram kidney weight with infusion at 10.0 ng/kg per minute. In summary, endothelin-1 infusion did not affect glomerular hydraulic pressure despite a fall in renal blood flow at low doses, but at high doses it reduced both, suggesting that endothelin-1 exerts separate, dose-dependent effects on preglomerular and postglomerular resistances. In addition, the present study demonstrated that endothelin-1 infusion has an ability to inhibit renin release in vivo when the macula densa-medlated pathway is eliminated. ndothelin-1 (ET-1) has been found in renal glomerular endothelial cells 1 and other kidney cells, 23 and it has specific binding sites in the glomeruli; therefore, the possibility has been raised that ET-1 may play some functional role in the regulation of renal hemodynamics. 4 In vivo, ET-1 has been reported to have potent renal vasoconstrictor effects, acting on both renal blood flow (RBF) and glomerular filtration rate (GFR) in dogs, rats, and rabbits.5 -7 Some studies have reported that in low doses the effects of ET-1 on RBF were much greater than those on GFR. In the studies by King et al 6 and Miura et al,8 ET-1 reduced RBF by as much as 20% and did not significantly alter GFR. These findings suggested that ET-1 had a predominant effect on the efferent arterioles, so that the glomerular capillary hydraulic pressure could be elevated or maintained despite the fall in RBF. King and Brenner 4 also found in rats that the transglomerular capillary pressure gradient was greater in the ET-1 infusion group than that in the control group. However, the direct effect of ET-1 on regulation of glomerular hydraulic pressure (GHP) over the complete dose range has not been fully analyzed. In addition to its potent renal vasoconstriction, ET-1 may have effects on the renin-angiotension system. Although many in vitro studies have found that ET-1 exerts an inhibitory effect on renin releas...

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“…In animal models of cardiac insufficiency, however, substantial increases in plasma endothelin-1 have been reported. 41,42 Therefore, the aim of the present study was to explore the possible contribution of endothelin-1 to hemodynamic compensation in humans, both in the short-term response to postural change and in the long-term adaptation to chronic cardiac insufficiency. Circulating levels of endothelin-1 and known neurohumoral mediators were determined at rest and during head-up tilt in normal subjects and patients with severe heart failure.…”

mentioning

confidence: 99%

Elevated endothelin-1 in heart failure and loss of normal response to postural change.

et al. 1992

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Background. The possible contribution of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, to neurohumoral compensation for hemodynamic stress was examined in nine normal volunteers and six patients with severe congestive heart failure.Methods and Results. Plasma levels of endothelin-1 were measured with a sensitive and specific radioimmunoassay. Venous blood samples were obtained after 90 minutes of supine rest and serially during 30 minutes of 60°upright tilt. Endothelin-1 levels were compared with those of known neurohumoral mediators of compensation. In normal subjects, the resting levels

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Endothelin in experimental congestive heart failure in the anesthetized dog

Cited by 58 publications

References 11 publications

Cardiac secretion of adrenomedullin in human heart failure.

Cardiac secretion of adrenomedullin in human heart failure.

Effect of endothelin-1 on glomerular hydraulic pressure and renin release in dogs.

Elevated endothelin-1 in heart failure and loss of normal response to postural change.

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