Differential Effects of Endothelin‐1 on Basal and Isoprenaline‐Enhanced Ca<sup>2+</sup> Current in Guinea‐Pig Ventricular Myocytes

Thomas, George P.; Sims, Stephen M.; Karmazyn, Morris

doi:10.1111/j.1469-7793.1997.055bi.x

Cited by 30 publications

(29 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These include a decrease [26,35], no change [15,36] or an increase [37,38]. In each of these atrial and ventricular studies in which basal and anti-adrenergic effects of ET-1 were compared [12][13][14][15]34,36,37], the most consistent and predominant effect was an anti-adrenergic reduction in I CaL . This has been shown to involve cAMP and G i protein in human atrial cells [14].…”

Section: /25mentioning

confidence: 99%

Anti-adrenergic effects of endothelin on human atrial action potentials are potentially anti-arrhythmic

Redpath

Rankin

Kane

et al. 2006

Journal of Molecular and Cellular Cardiology

View full text Add to dashboard Cite

Abstract.Endothelin-1 (ET-1) is elevated in patients with atrial fibrillation (AF) and heart failure. We investigated effects of ET-1 on human atrial cellular electrophysiological measurements expected to influence the genesis and maintenance of AF. Action potential characteristics and L-type Ca 2+ current (I CaL ) were recorded by whole cell patch clamp, in atrial isolated myocytes obtained from patients in sinus rhythm. Isoproterenol (ISO) at 0.05 µM prolonged the action potential duration at 50% repolarisation (APD 50 : 54±10 vs 28±5 ms; P<0.05, n=15 cells, 10 patients), but neither late repolarisation nor cellular effective refractory period (ERP) were affected. ET-1 (10 nM) reversed the effect of ISO on APD 50 , and had no basal effect (in the absence of ISO) on repolarisation or ERP. During repetitive stimulation, ISO (0.05 µM) produced arrhythmic depolarisations (P<0.05). Each was abolished by ET-1 at 10 nM (P<0.05). ISO (0.05 µM) increased peak I CaL from -5.5±0.4 to -14.6±0.9 pA/pF (P<0.05; n=79 cells, 34 patients). ET-1 (10 nM) reversed this effect by 98±10% (P<0.05), with no effect on basal I CaL . Chronic treatment of patients with a β-blocker did not significantly alter basal APD 50 or I CaL , the increase in APD 50 or I CaL by 0.05 µM ISO, nor the subsequent reversal of this effect on APD 50 by 10 nM ET-1. The marked anti-adrenergic effects of ET-1 on human atrial cellular action potential plateau, arrhythmic depolarisations and I CaL , without affecting ERP and independently of β-blocker treatment, may be expected to contribute a potentially anti-arrhythmic influence in the atria of patients with AF and heart failure.

show abstract

Section: /25mentioning

confidence: 99%

Anti-adrenergic effects of endothelin on human atrial action potentials are potentially anti-arrhythmic

Redpath

Rankin

Kane

et al. 2006

Journal of Molecular and Cellular Cardiology

View full text Add to dashboard Cite

show abstract

“…42,43 Taken together, our in vivo and in vitro studies suggest that stimulation of ETA-R contributes to the Ang II-mediated suppression of renal mechanosensory nerves by a mechanism distal to renal pelvic PGE 2 synthesis. In view of our and other investigators' studies, 11,[37][38][39][40][41] we hypothesize that Ang II activates AT1-R, resulting in increased activation of ETA-R, which, in turn, suppresses the PGE 2 -mediated release of substance P and activation of renal mechanosensory nerves by a PTX-sensitive mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…37 Likewise, in gall bladder epithelial cells, ET-1 reduces cAMP accumulation by a PTX-sensitive mechanism. 38 ET-1-mediated activation of ETA-R inhibits voltagesensitive Ca ϩϩ channels in cultured cerebellar neurons 39 and the isoproterenol-induced increases in L-type Ca ϩϩ current in ventricular myocytes, 40,41 the latter involving a PTX-sensitive mechanism.…”

Section: Discussionmentioning

confidence: 99%

Activation of Endothelin-A Receptors Contributes to Angiotensin-Induced Suppression of Renal Sensory Nerve Activation

2007

View full text Add to dashboard Cite

Abstract-Activation of renal mechanosensory nerves is enhanced by a high-sodium diet and suppressed by a low-sodium diet. Angiotensin (Ang) II and endothelin (ET)-1 each contributes to the impaired responsiveness of renal mechanosensory nerves in a low-sodium diet. We examined whether stimulation of ETA receptors (Rs) contributes to Ang II-induced suppression of the responsiveness of renal mechanosensory nerves. In anesthetized rats fed a low-sodium diet, renal pelvic administration of the Ang type I receptor (AT1-R) antagonist losartan enhanced the afferent renal nerve activity (ARNA) response to increasing renal pelvic pressure 7.5 mm Hg from 7Ϯ2% to 15Ϯ2% and the prostaglandin (PG) E 2 -mediated substance P release from 0Ϯ1 to 8Ϯ1 pg/min. Adding the ETA-R antagonist BQ123 to the renal pelvic perfusate containing losartan did not produce any further enhancement of the ARNA response or PGE 2 -mediated release of substance P (17Ϯ3% and 8Ϯ1 pg/min). Likewise, renal pelvic administration of BQ123 and BQ123ϩlosartan resulted in similar enhancements of the ARNA responses to increased renal pelvic pressure and PGE 2 -mediated substance P release. In high-sodium-diet rats, pelvic administration of Ang II reduced the ARNA response to increased renal pelvic pressure from 27Ϯ4% to 8Ϯ3% and the PGE 2 -mediated substance P release from 9Ϯ0 to 1Ϯ1 pg/min. Adding BQ123 to the renal pelvic perfusate containing Ang II restored the increases in ARNA and the PGE 2 -mediated substance P release toward control (27Ϯ6% and 7Ϯ1 pg/min). In conclusion, stimulation of ETA-R plays an important contributory role to the Ang II-mediated suppression of the activation of renal mechanosensory nerves in conditions of low-sodium diet. Key Words: ETA-receptors Ⅲ AT1-receptors Ⅲ afferent renal nerves Ⅲ PGE 2 Ⅲ substance P Ⅲ BQ123 Ⅲ losartan T he majority of the afferent renal nerves are located in the renal pelvic wall. 1-3 Activation of these nerves by increases in renal pelvic pressure results in increases in afferent renal nerve activity (ARNA) leading to reflex decreases in efferent renal sympathetic nerve activity and diuresis and natriuresis, that is, a renorenal reflex response. 4 Among the various mechanisms activated by stretching the renal pelvic wall is induction of cyclooxygenase-2 resulting in increased renal pelvic synthesis of PGE 2 . 5,6 PGE 2 leads to activation of the cAMP-protein kinase A transduction pathway and a release of the neuropeptide substance P, which activates the afferent renal nerves by stimulating neurokinin-1 receptors in the renal pelvic area. 1,7,8 The responsiveness of the afferent renal nerves is enhanced by high-sodium diet and suppressed by low-sodium diet because of an interaction between prostaglandin (PG) E 2 (PGE 2 ) and angiotensin (Ang) II at the peripheral renal sensory nerve endings. 7,9,10 In conditions of high-sodium diet, characterized by low endogenous Ang II, 11 there is little or no inhibition of the PGE 2 -mediated activation of adenylyl cyclase. Conversely, in conditions of low-sodium diet, ...

show abstract

“…The sustained NIE of ET-1 is elicited in most mammalian species, including guinea pig (28,29), rat (28), rabbit (24), and dog (14,30). Effectiveness of selective ET A antagonists to inhibit the inhibitory effect of ET-1 on the NE-induced PIE in the current study is consistent with the previous findings that ET A antagonists suppressed the inhibitory action of ET-1 on the b-mediated increase in I Ca(L) currents in guinea pig (31,32), rabbit (24), and dog (14) ventricular cardiomyocytes.…”

Section: Sustained Pie Of Et-1 Induced By Crosstalk With Ne At Low Comentioning

confidence: 99%

Receptor Subtypes Mediating the Inotropic Effects and Ca2+ Signaling Induced by Endothelin-1 Through Crosstalk With Norepinephrine in Canine Ventricular Myocardium

et al. 2005

View full text Add to dashboard Cite

Abstract. In canine ventricular myocardium, endothelin-1 (ET-1) alone induced only a weak transient negative inotropic effect (NIE). However, ET-1 induced a marked sustained positive inotropic effect (PIE) subsequent to a transient NIE in the presence of norepinephrine (NE) at low concentrations (0.1 -1 nM) and elicited a pronounced sustained NIE in the presence of NE at high concentrations (around 100 nM). Thus, the extent of b-adrenoceptor stimulation induced by NE played a crucial role in determining the characteristics of the inotropic effects of ET-1. The characteristics of ET receptor subtypes involved in contractile regulation and Ca 2+ signaling induced by ET-1 were determined. The ET-1-induced transient NIE and decrease in Ca transients were abolished by the selective ET A -receptor antagonist FR319317, but not by the selective ET B -receptor antagonist BQ-788. The sustained PIE and the increase in Ca 2+ transients induced by ET-1 were abolished by FR319317, but not inhibited by BQ-788. In contrast, the sustained NIE of ET-1 was abolished by the non-selective ET antagonist TAK-044, markedly attenuated by FR319317, and partially inhibited by BQ-788. ET-1 alone elicited a PIE in the presence of BQ-788, which indicates that the activation of ET B -receptors counteracts the development of the PIE of ET-1. The current findings indicate that both ET A and ET B receptors are involved in the regulation of Ca 2+ signaling and contractility in canine ventricular myocardium.

show abstract

Differential Effects of Endothelin‐1 on Basal and Isoprenaline‐Enhanced Ca²⁺ Current in Guinea‐Pig Ventricular Myocytes

Cited by 30 publications

References 38 publications

Anti-adrenergic effects of endothelin on human atrial action potentials are potentially anti-arrhythmic

Anti-adrenergic effects of endothelin on human atrial action potentials are potentially anti-arrhythmic

Activation of Endothelin-A Receptors Contributes to Angiotensin-Induced Suppression of Renal Sensory Nerve Activation

Receptor Subtypes Mediating the Inotropic Effects and Ca2+ Signaling Induced by Endothelin-1 Through Crosstalk With Norepinephrine in Canine Ventricular Myocardium

Contact Info

Product

Resources

About

Differential Effects of Endothelin‐1 on Basal and Isoprenaline‐Enhanced Ca2+ Current in Guinea‐Pig Ventricular Myocytes

Cited by 30 publications

References 38 publications

Anti-adrenergic effects of endothelin on human atrial action potentials are potentially anti-arrhythmic

Anti-adrenergic effects of endothelin on human atrial action potentials are potentially anti-arrhythmic

Activation of Endothelin-A Receptors Contributes to Angiotensin-Induced Suppression of Renal Sensory Nerve Activation

Receptor Subtypes Mediating the Inotropic Effects and Ca2+ Signaling Induced by Endothelin-1 Through Crosstalk With Norepinephrine in Canine Ventricular Myocardium

Contact Info

Product

Resources

About

Differential Effects of Endothelin‐1 on Basal and Isoprenaline‐Enhanced Ca²⁺ Current in Guinea‐Pig Ventricular Myocytes