Characterization of Big Endothelin-1-Induced Contraction in Rabbit Saphenous Artery

Ferlenga, Pierpaolo; Morazzoni, Gabriele; Ros, Bienvenido; Branca, Enrica; Fantoni, M; Marchini, Francesco; Pocchiari, F.; Semeraro, C.

doi:10.1097/00005344-199506263-00025

Cited by 3 publications

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“…Functional evidence in our study showing the almost equal to 50% reduction in constriction of denuded retinal arterioles to big ET-1 supports the equal importance of endothelial and smooth muscle layers contributing to the overall production of ET-1. In contrast with our findings, vasoconstriction to big ET-1 was shown to be endothelium-independent in porcine coronary arteries, 29 and in rabbit basilar 30 and saphenous 31 arteries. Hence, an essentially equal functional role for endothelium and smooth muscle in processing exogenous big ET-1 to vasoactive ET-1 appears to be a unique feature of the retinal arterioles.…”

Section: Discussioncontrasting

confidence: 99%

Role of Endothelium in Vasomotor Responses to Endothelin System and Protein Kinase C Activation in Porcine Retinal Arterioles

Potts

Bradley

et al. 2013

Investigative Ophthalmology & Visual Science

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PURPOSE. Endothelial cells synthesize vasodilator nitric oxide (NO) and vasoconstrictor endothelin-1 (ET-1) from NO synthase (eNOS) and endothelin-converting enzyme-1 (ECE-1), respectively. Protein kinase C (PKC) and Rho kinase (ROCK) are major signaling molecules mediating vasoconstriction. Although endothelial cells express eNOS, ECE-1, endothelin B (ET B ) receptors, PKC, and ROCK, their influences on ET-1-induced vasoconstriction remain elusive. We studied whether these endothelial signaling molecules modulate retinal arteriolar constriction to ET-1. METHODS.Porcine retinal arterioles were isolated and pressurized for vasomotor study, under conditions with intact or denuded endothelium, using videomicroscopic techniques. RESULTS.Retinal arterioles developed similar resting tone (»45% of maximum diameter) with or without endothelium. Endothelial denudation attenuated vasoconstriction to ET-1 precursor, big ET-1, by almost equal to 50%, but did not affect vasoconstrictions to ET-1, ET B agonist sarafotoxin S6c, or PKC activator phorbol-12, 13-dibutyrate (PDBu). The ROCK inhibitor H-1152 caused vasodilation, and abolished vasoconstrictions to ET-1 and PDBu independent of endothelium. With L-type voltage-operated calcium channel (L-VOCC) blocker nifedipine, PDBu-induced vasoconstriction was abolished and converted to NO-mediated vasodilation in the presence of endothelium. The ET-1-induced vasoconstriction was unaffected by NO released from endothelium during flow elevation.CONCLUSIONS. Endothelial and smooth muscle ECE-1 contribute equally to synthesis of vasoactive ET-1 in retinal arterioles, with nominal role of endothelial ET B receptors in vasoconstriction to ET-1. The PKC activation leads to endothelium-dependent NO-mediated vasodilation when smooth muscle contraction is ablated by L-VOCC blockade. Endothelial cells and NO appear to have modest roles in modulating ROCK-dependent vasoconstriction, and are insufficient to counteract smooth muscle contractions to ET-1 and PKC activation.

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Section: Discussioncontrasting

confidence: 99%

Role of Endothelium in Vasomotor Responses to Endothelin System and Protein Kinase C Activation in Porcine Retinal Arterioles

Potts

Bradley

et al. 2013

Investigative Ophthalmology & Visual Science

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Contractile effect of big endothelin-1 and its conversion to endothelin-1 in rabbit cerebral arteries

Petersson¹,

Hanson

Lindberg

et al. 1996

Naunyn-Schmiedeberg's Arch Pharmacol

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The effect of big endothelin-1 (big ET-1) and its conversion to endothelin-1 (ET-1) in rabbit cerebral arteries were examined. Big ET-1 and ET-1 induced concentration-dependent contractions in the basilar artery; ET-1 was approximately 8 times more potent than big ET-1. The metalloprotease inhibitor phosphoramidon (30 mumol/l) almost abolished the contractile response to big ET-1, whereas the ET-1-induced contraction was unaffected. Removal of the endothelium did not attenuate the big ET-1-induced contraction. ET-1 was approximately 14 times more potent than endothelin-3 (ET-3) to elicit contraction. The contractions induced by big ET-1, ET-1 and ET-3 were all inhibited by ET(A) receptor antagonist BQ 123 (3 mumol/l). The ET(B) receptor antagonist IRL 1038 (3 mumol/l) had no effect on the contractile responses to big ET-1 and ET-1, but produced a small inhibition of the ET-3-induced contraction. Formation of ET-1 was demonstrated in membrane fractions of cerebral arteries incubated with big ET-1 as measured by high pressure liquid chromatography followed by radioimmunoassay. These results suggest that externally applied big ET-1 is converted to ET-1 by a phosphoramidon-sensitive "endothelin converting enzyme" present in the vascular smooth muscle cells. The ET-1 formed subsequently mediates the big ET-1-induced contraction by activation of mainly ET(A) receptors, although a small contribution of ET(B) receptors cannot be excluded.

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Role of Endothelium in Vasomotor Responses to Endothelin System and Protein Kinase C Activation in Porcine Retinal Arterioles

Potts

Bradley

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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Endothelial and smooth muscle ECE-1 contribute equally to synthesis of vasoactive ET-1 in retinal arterioles, with nominal role of endothelial ETB receptors in vasoconstriction to ET-1. The PKC activation leads to endothelium-dependent NO-mediated vasodilation when smooth muscle contraction is ablated by L-VOCC blockade. Endothelial cells and NO appear to have modest roles in modulating ROCK-dependent vasoconstriction, and are insufficient to counteract smooth muscle contractions to ET-1 and PKC activation.

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Characterization of Big Endothelin-1-Induced Contraction in Rabbit Saphenous Artery

Cited by 3 publications

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Role of Endothelium in Vasomotor Responses to Endothelin System and Protein Kinase C Activation in Porcine Retinal Arterioles

Role of Endothelium in Vasomotor Responses to Endothelin System and Protein Kinase C Activation in Porcine Retinal Arterioles

Contractile effect of big endothelin-1 and its conversion to endothelin-1 in rabbit cerebral arteries

Role of Endothelium in Vasomotor Responses to Endothelin System and Protein Kinase C Activation in Porcine Retinal Arterioles

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