Ischaemia causes externalization of endothelin-1 binding sites in rat cardiac membranes

Liu, Jianjun; Casley, David; Nayler, Winifred G.

doi:10.1016/0006-291x(89)91799-3

Cited by 56 publications

(19 citation statements)

References 21 publications

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“…Recently, it has been reported that cardiac ischaemia causes externalization of endothelin binding sites (Liu, Casley & Nayler, 1989). Therefore further studies will be needed to examine the possible increase in endothelin binding-site density on renal cells membranes under these conditions.…”

Section: Discussionmentioning

confidence: 99%

A role for endothelin in the maintenance of post‐ischaemic renal failure in the rat.

López‐Farré

Gómez‐Garre

Bernabeu

et al. 1991

The Journal of Physiology

102

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SUMMARY1. Endothelin (ET) has been shown to reduce glomerular filtration rate (GFR) and renal blood flow (RBF) and may therefore be a possible mediator of the reduction of GFR and RBF observed in post-ischaemic acute renal failure.2. We infused a specific ET antibody, i.v., for 1 h before and 1 h after a 60 min period of renal ischaemia by clamping the renal artery, and observed the changes in renal function (acute clearance and long-term metabolic cage studies) compared with rats infused with non-immune rabbit serum.3. In acute and long-term studies, better renal function, as judged by GFR and RBF was observed in rats treated with the ET antibody. Furthermore, ischaemic rats showed higher levels of plasma immunoreactive ET (7-02 + 1-17 pg ET (ml plasma)-'; mean+ S.E.M.) than normal rats where it was undetected.4. We previously reported that glomeruli and renal platelet-activating factor (PAF) production were increased after renal ischaemia. So, we studied the possible relationship between ET and glomeruli or renal PAF production in post-ischaemic acute renal failure.5. Glomeruli from ischaemic rats produced greater amounts of PAF than glomeruli from normal or anti-ET antibody-treated ischaemic rats. In addition, total renal PAF production was higher in ischaemic-untreated than in non-ischaemic or anti-ET-treated rats. Glomeruli incubated with 10-7 M-endothelin produced much more PAF than those incubated in control conditions (138-4 + 10-5 vs. 80-2 +9-4 pg PAF (mg protein) 1; means +S. E. M.; n = 10).6. In conclusion, the present study suggests that endothelin plays a role in the persistent renal vasoconstriction that characterizes post-ischaemic acute renal failure. In addition, the observed increase in glomerular PAF production after renal ischaemia may be due to the action of endothelin.

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Section: Discussionmentioning

confidence: 99%

A role for endothelin in the maintenance of post‐ischaemic renal failure in the rat.

López‐Farré

Gómez‐Garre

Bernabeu

et al. 1991

The Journal of Physiology

102

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“…Therefore it seems likely that the greater constriction found in hypoxia is largely due to increased sensitivity of the vascular smooth muscle to endothelin-1, or due to the facilitatory effects of a factor released by hypoxia. The former mechanism is known to occur in the heart where ischaemia causes an increase of endothelin-1 receptors in the plasma membrane (Liu et al, 1989;1990 (Warner et al, 1989;Randall et al, 1989). This is thought to be due to the loss of tonically released EDRF, which may modulate vasoconstriction, or due to the loss of EDRF release stimulated by endothelin-l itself.…”

Section: Discussionmentioning

confidence: 99%

“…In the pithed rat MacLean et al (1989) have shown that the potency of endothelin-1 as a vasoconstrictor in the intact mesenteric arterial bed is doubled in hypoxia produced by lowering the ventilation volume. Also, Liu et al (1989;1990) have demonstrated that global cardiac ischaemia, but not hypoxia, increases the proportion of endothelin-1 binding sites in the cardiac plasma membrane due to the movement of receptors from the cytosol. In view of the possibility of hypoxic facilitation of vascular responses to endothelin-1 the activity of the peptide was studied in the rabbit ear under hypoxic conditions.…”

Section: Introductionmentioning

confidence: 99%

Activities of endothelin‐1 in the vascular network of the rabbit ear: a microangiographic study

Randall¹,

Edwards

Griffith³

1990

British J Pharmacology

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1 The effects of endothelin-1 on perfusion pressure and on arterial and venous diameters were examined simultaneously in a rabbit isolated ear preparation perfused with physiological buffer. The effects of hypoxia and inhibition of endothelium-derived relaxant factor (EDRF) activity on vascular responses to endothelin-1 were also investigated.2 Endothelin-1 was potent at increasing perfusion pressure (ED50 = 46.7 + 11.0 pmol; R.,, = 85.3 + 5.3 mmHg). The potency and maximum reactivity were not significantly affected by hypoxia, inhibition of EDRF activity with 50,UM N-nitro-L-arginine methyl ester (NAME) or a combination of hypoxia and NAME. 3 Endothelin-1 caused equipotent dose-dependent constrictions of the first four generations of arterial branch vessels (G1-G4) but did not influence the diameter of the central ear artery except at high doses of the peptide when 'paradoxical dilatation' was observed. The peptide was also equipotent at causing constriction of the smaller venous vessels (V1-V4) but did not affect the large veins (VO). 4 Under conditions of hypoxia the potency of endothelin-1 was reduced in G2 and G3, was unaffected in G4 and the peptide did not significantly constrict either Go or G1. Hypoxia reduced the potency of endothelin-1 in the smaller venous vessels (V1-V4), but conversely unmasked a marked constriction of the large veins (VO), which was not observed under normoxic conditions. 5 NAME 5OpUM abolished the vasodilator effects of acetylcholine in this preparation. Inhibition of EDRF activity with NAME under normoxic conditions did not influence the constrictor activity of endothelin-1 on the arterial or venous branch vessels. However, inhibition of EDRF activity under hypoxic conditions prevented the reduction of potency of endothelin-1 as a constrictor of arterial and venous branch vessels which occurred in hypoxia. In the presence of NAME endothelin-1 constricted VO in both normoxia and hypoxia with equipotency but the maximum effect was greatest in hypoxia. 6 In conclusion, endothelin-1 is a powerful vasoconstrictor which acts with greater potency in veins than arteries in the rabbit isolated ear. Although hypoxia does not influence pressor responses it nevertheless alters the spatial pattern of vasoconstriction. In particular hypoxia unmasks constriction of the large veins by endothelin-1. Constriction of these veins was also observed in the absence of EDRF in normoxia, but to a much lesser degree so that the effect of hypoxia may only be partially due to reduced EDRF activity. Hypoxia may therefore directly or indirectly increase the sensitivity of the main veins to endothelin-1.

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“…Ischemia, which is a complication of atherosclerotic vascular disease, further stimulates the release of endothelin as well as externalization of endothelin binding sites. 67 ' 68 This indirect evidence (which obviously awaits the results of trials with a specific antagonist) strongly suggests a role of endothelin in complications of the hypertensive process.…”

Section: Does Endothelin Contribute To Hypertensivementioning

confidence: 98%

Potential role of endothelin in hypertension. Controversy on endothelin in hypertension.

1993

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T he hallmark of hypertension is an increase in peripheral vascular resistance. 1 This increase is considered to be related to an increase in tone of resistance arteries as well as to structural changes (i.e., vascular remodeling) of these blood vessels. Accordingly, hypertension research has focused on identifying the mediator or mediators responsible for this phenomenon. Although several possible candidates have been extensively studied, in particular the renin-angiotensin system and catecholamines, no definite answer has been found. Hence, the search for additional mediators or the mediator causing the increase in peripheral vascular resistance in hypertension continues.In addition to the increase in peripheral vascular resistance, hypertension is associated with cardiovascular complications such as myocardial infarction and stroke. In both syndromes, severe ischemia to these vital organs is responsible for the clinical syndrome. Again, structural and functional alterations of the supplying circulation are held responsible. In contrast to the increase in peripheral vascular resistance, however, these changes are primarily seen in certain (i.e., coronary and cerebral) vascular beds rather than in the entire circulation.The question of whether endothelin is involved in hypertension, its complications, or both cannot be solved at this point; however, several aspects can be addressed. Can Endothelin Induce Hypertension?When infused intravenously, endothelin causes a rapid and transient vasodilation followed by a profound and long-lasting increase in blood pressure.2 " 4 This increase in blood pressure is dose dependent, occurs at much lower concentrations than with any other vasoconstrictor hormone, and also is remarkably long-lasting. In vitro experiments have demonstrated that this increase in blood pressure is related to profound vasoconstriction of resistance arteries of different vascular beds of the circulation. -6 Although the vasodilator effects of endothelin are related to activation of endothelin B-receptors 7 -8 linked to the formation of prosta-

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Ischaemia causes externalization of endothelin-1 binding sites in rat cardiac membranes

Cited by 56 publications

References 21 publications

A role for endothelin in the maintenance of post‐ischaemic renal failure in the rat.

A role for endothelin in the maintenance of post‐ischaemic renal failure in the rat.

Activities of endothelin‐1 in the vascular network of the rabbit ear: a microangiographic study

Potential role of endothelin in hypertension. Controversy on endothelin in hypertension.

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