Potentiation of norepinephrine-induced contractions by endothelin-1 in the rabbit aorta.

Abstract

Subthreshold concentrations of endothelin-1 potentiated the norepinephrine-induced contraction in isometrically mounted rings of the rabbit aorta. Pretreatment with endothelin-1 (0.1 nM) for 10 minutes increased the sensitivity of the aortic rings to norepinephrine without affecting the maximal contraction. This amplification was unaffected by removal of the endothelium but was prevented by the protein kinase C inhibitors staurosporine (0.01 (iM) and calphostin C (0.1 fiM). Pretreatment of the aortic rings for 24 hours with phorbol 12-myristate 13-acetate (0.1 fiM) also abolished the potentiation. Norepinephrineinduced contraction was potentiated by pretreating with phorbol 12-myristate 13-acetate (10 nM) and by increasing the concentration of K + in the bath solution from 4.6 to 8.6 mM. The potentiation of the norepinephrine-induced contraction by endothelin-1 (0.1 nM) or by phorbol 12-myristate 13-acetate (10 nM) was not associated with an increase in norepinephrine-induced 45 Ca 2+ uptake or influx, whereas the potentiation due to an increase in the concentration of K + in the bath solution from 4.6 to 8.6 mM was associated with an increase in norepinephrine-induced 45 Ca 2+ uptake. We conclude that endothelin-1 potentiation of the norepinephrine-induced contraction occurs in the absence of changes in stimulated Ca 2+ entry and is endothelium independent. It is probable that endothelin-1 increases the sensitivity of the contractile apparatus to Ca 2+ by activating protein kinase C-dependent mechanisms. produced by endothelial cells. 1 Its direct contractile effect has been widely studied, although it is not yet completely understood.2 On the other hand, subthreshold concentrations of ET-1, compatible with the plasma level, 3 potentiate the contractile effect of different agonists such as norepinephrine in human arteries 4 and rat mesenteric beds 5 -6 and serotonin in rat aortic rings 7 and pulmonary arteries. 8 Such a phenomenon might have a pathological importance since it could be involved in hypertension and vasospastic syndrome.4 Indeed, the potentiation of serotonininduced contractions by ET-1 might increase the vasospasms induced by aggregating platelets. Moreover, there is a positive correlation between ET-1 plasma level and systolic blood pressure in humans, 9 and the vascular production of ET-1 under angiotensin II (Ang II) stimulation is higher in hypertensive than in normotensive rats. 10 The amplification is nevertheless blocked by Ca 2+ entry blocker in human arteries 4 and in the rat mesenteric bed. 6 In contrast, the direct effect of ET-1 is relatively insensitive to Ca 2+ entry blockers.

Preproendothelin-1 Gene Polymorphism Is Related to a Change in Vascular Reactivity in the Human Mammary Artery In Vitro

“…This is in agreement with previous studies that have demonstrated the occurrence of the phenomenon in vitro [15][16][17][18]22,23 or in vivo, 14,19 -21 as well as in humans. 14,20 -23 We have previously shown that this potentiation involves a sensitization of the contractile apparatus to calcium through the activation of protein kinase C. 15,17 Furthermore, we and others have also previously reported that endogenous endothelin-1 25 and angiotensin II 19 -21 take part in the control of vascular tone in resistance arteries and that the concentrations of hormones used in the present study are compatible with endogenous concentrations. Hence, role of endothelin-1 in the control of vascular tone can be altered, considering that vascular levels of endothelin-1 are modified in pathological situations such as hypertension.…”

“…Indeed, concentrations of endothelin-1 in the picomolar range are able to amplify the adrenergic-dependent tone through a reversible mechanism that does not change the amount of calcium required for the contraction. 15 In addition, as high K ϩ -induced contractions were similar in both groups, an alteration in the contractile apparatus should be excluded. We also found that both endothelium-dependent and -independent relaxations were unaffected by the mutation.…”

“…[2][3][4][5][6][7][8][9][10][11][12][13] At subthreshold concentrations, within the physiological (picomolar) range, endothelin-1 has no direct contractile effect but induces a potent amplification of ␣-adrenergicdependent vascular tone. 14,15 This amplification by endothelin-1 involves a sensitization of the contractile apparatus to calcium 15 and has been described in animals 15 and humans. 14 This phenomenon represents a mechanism by which endothelin-1 can modulate vascular tone without inducing the long-lasting and irreversible contraction as classically described for endothelin-1.…”

Endothelin (ET)-1-Induced Inhibition of ATP Release from PC-12 Cells Is Mediated by the ETBReceptor: Differential Response to ET-1 on ATP, Neuropeptide Y, and Dopamine Levels

“…In the rat mesenteric bed, ET-1 negatively modulates the release of NPY, but not NE (Hoang et al, 2002). Postjunctionally, ETs modulate sympathetic neurotransmission by enhancement of the contractile effect of both nerve stimulation and a variety of vasoactive agents (Henrion and Laher, 1993;Hoang et al, 2003). ET-1, through activation of the ET A receptor, potentiates the postjunctional contractile effects of ATP (Mutafova-Yambolieva and Radomirov, 1993;Hoang et al, 2003).…”

Reduction of renal mass is lethal in mice lacking vimentin. Role of endothelin-nitric oxide imbalance.

“…Briefly, second order renal arteries were dissected, and segment rings (2 mm) were prepared and mounted on nylon filaments in a myograph for resistance arteries (24). Segments of thoracic aorta (3 mm) were dissected and mounted on stainless steel wires in a classic myograph (25). Isometric tension was recorded using a force displacement transducer (MP 100; BioPac Systems, Inc., La Jolla, CA).…”