The mechanism of action of endothelin-1 as compared with other agonists in vascular smooth muscle

Journal Article · Sat Dec 31 23:00:00 EST 1988 · Journal of Cardiovascular Pharmacology; (USA)

DOI:https://doi.org/10.1097/00005344-198900135-00008· OSTI ID:5189703

Wallnoefer, A W; Weir, S; Rueegg, U C; Cauvin, C ^[1]

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1. Sandoz, Ltd., Basel (Switzerland)

The effects of endothelin-1 (ET-1) on tension and membrane potential in rat isolated mesenteric resistance vessels (MRVs) and on 45Ca influx, 45Ca efflux, inositol-1,4,5-triphosphate (IP3) production, and cytoplasmic Ca2+ concentration ((Ca2+)1) in cultured aortic smooth muscle cells were compared with those of other agonists. ET-1 induced contractions of the MRVs, which were slow in onset, but reached a similar maximum amplitude (at 10 nM ET-1) as that seen with norepinephrine (NE, 10 microM) or (arg8)vasopressin (AVP, 0.1 microM). The EC50 for ET-1 was 1.3 +/- 0.1 nM. Removal of extracellular Ca2+ reduced ET-1-induced contractions to 11 +/- 3% of those in Ca2+-containing medium. With NE, the same procedure reduced contractions to 47 +/- 7% of those in Ca2+-containing medium, while with AVP, the reduction was similar in magnitude to that induced by ET-1 (11 +/- 5% of those in Ca2+-containing medium). Relaxation of ET-1-induced and NE-induced contractions by diltiazem was not complete (maximal at 58 +/- 6% with 10 microM diltiazem after 6 nM ET-1, and at 70 +/- 3% after 0.1 microM NE), in contrast to that of 80 mM K+-induced contractions, which were potently (IC50 = 0.2 microM) and completely reversed (100% relaxation at 10 microM diltiazem). ET-1 (6 nM) caused a small but significant depolarization of the MRVs (approximately 7 mV), the magnitude of which was only about one-third of that induced by equieffective contractile concentrations of NE and AVP. The voltage-sensitive Ca2+ channel agonist Bay K 8644 (1 microM), in contrast to ET-1, NE, and AVP, produced a small contraction (30 +/- 2% of the maximum response to NE), but no further depolarization when added in the presence of 15 mM K+ (which elicited approximately 12 mV depolarization but no contraction).

• OSTI ID: 5189703
• Journal Information: Journal of Cardiovascular Pharmacology; (USA), Journal Name: Journal of Cardiovascular Pharmacology; (USA) Vol. 13 Suppl 5; ISSN 0160-2446; ISSN JCPCD
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ALKALI METAL COMPOUNDS
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
ANIMALS
AORTA
ARTERIES
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BLOOD VESSELS
BODY
CALCIUM 45
CALCIUM COMPOUNDS
CALCIUM ISOTOPES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
CHLORIDES
CHLORINE COMPOUNDS
COMPARATIVE EVALUATIONS
CONTRACTION
DAYS LIVING RADIOISOTOPES
DRUGS
ESTERS
EVEN-ODD NUCLEI
HALIDES
HALOGEN COMPOUNDS
HORMONES
IN VITRO
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIPIDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
MUSCLES
NEUROREGULATORS
NORADRENALINE
NUCLEI
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PEPTIDE HORMONES
PEPTIDES
PHOSPHOLIPIDS
PITUITARY HORMONES
PORINS
POTASSIUM CHLORIDES
POTASSIUM COMPOUNDS
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RODENTS
SYMPATHOMIMETICS
TRACER TECHNIQUES
VASOCONSTRICTORS
VASODILATORS
VASOPRESSIN
VERTEBRATES