Endothelin-1-mediated wave-like [Ca2+]i oscillations in intact rabbit inferior vena cava.
Endothelin-1 (ET1) is an endogenous vasoconstrictor released by the vascular system to regulate the contractility of vascular smooth muscle cells (VSMC). It is implicated in the pathogenesis of hypertension and diabetic vasculopathy. In rabbit inferior vena cava (IVC), 10 nM ET1 induces tonic contraction mainly via type A endothelin receptor activation. Using confocal imaging of Fluo-3 loaded in thein situ VSMC within the intact IVC, we found that ET1 elicited [Ca2+]i oscillations with an average frequency of 0.31 +/- 0.01 Hz. These [Ca2+]i oscillations occurred as repetitive Ca2+ waves traveling along the longitudinal axis of the cells with an average velocity of 29 +/- 3 microm/s. The Ca2+ waves were not synchronized between neighboring VSMC nor were they propagated between them. Nifedipine (10 microM) inhibited the tonic contraction by 27.0 +/- 5.0% while SKF96365 (50 microM) abolished the remaining contraction. In a parallel Ca2+ study, nifedipine reduced the frequency of the oscillations to 0.22 +/- 0.01 Hz while SKF96365 abolished the remaining [Ca2+]i oscillations. Subsequent application of 25 mM caffeine elicited no further Ca2+ signal. Thus, we conclude that ET1 stimulates tonic contraction in the rabbit IVC by inducing [Ca2+]i oscillations and that stimulated Ca2+ entry through both the L-type voltage-gated Ca2+ channels and a nifedipine-resistant and SKF96365-sensitive pathway is crucial for the maintenance of [Ca2+]i oscillations and tonic contraction.
The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Vancouver, B.C., Canada.
Jiazhen
J
Dai
Cheng-Han
CH
Lee
Damon
D
Poburko
Tania
T
Szado
Kuo-Hsing
KH
Kuo
Cornelis
C
van Breemen
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D044022:Receptor, Endothelin A / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000378:metabolism* / Q000494:pharmacology; D014682:Vena Cava, Inferior / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D019332:Endothelin-1; D007093:Imidazoles; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D014662:Vasoconstrictor Agents; C086539:BQ 788; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)