Endothelial cell-derived vasoconstrictors: Mechanisms of action in vascular smooth muscle

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

DOI:https://doi.org/10.1097/00005344-198900135-00010· OSTI ID:5405523

Highsmith, R F; Pang, D C; Rapoport, R M ^[1]

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1. Univ. of Cincinnati, OH (USA)

Intercellular signaling between the endothelial cell (EC) and vascular smooth muscle (VSM) is an important determinant of vasomotor tone. We evaluated mechanisms of action of EC-derived constrictors on VSM using conditioned medium from bovine aortic ECs in culture (EC-CM) or endothelin-1 (ET-1), and isolated coronary arteries or cultured VSM cells. EC-CM enhanced Ca2+ uptake into monolayers of rat aortic VSM and elicited sustained contractions in isolated coronary vessels in a time- and dose-dependent manner. The enhanced Ca2+ uptake and contractions were markedly attenuated by the Ca2+ channel antagonists bepridil, verapamil, and nitrendipine. EC-CM and ET-1 resulted in VSM membrane depolarization and increased excitability to electrical stimulation that was blocked by verapamil. ET-1 and EC-CM induced a dose-dependent increase in steady-state (Ca2+)i in Fura-2-loaded rat VSM cells. Most VSM responded with a rapid and transient increase in (Ca2+)i while others lacked only the transient phase. The elevated poststimulus (Ca2+)i level appeared to precede the influx of extracellular Ca2+ and contraction. EC-CM and ET-1 also resulted in time- and concentration-dependent increases in inositol monophosphate (IP) formation in rat aorta that paralleled the development of isometric force. We propose a biphasic mechanism in which the stable constrictors present in EC-CM elicit a rapid, phospholipase C-mediated mobilization of intracellular Ca2+ accompanied by or coupled to a sustained influx of extracellular Ca2+ through voltage-dependent channels.

• OSTI ID: 5405523
• 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

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METAL COMPOUNDS
ANIMALS
BIOCHEMICAL REACTION KINETICS
CALCIUM COMPOUNDS
CALCIUM ISOTOPES
CARDIOVASCULAR AGENTS
CATTLE
CONTRACTION
DOMESTIC ANIMALS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ESTERS
IN VITRO
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIPIDS
MAMMALS
MEMBRANE TRANSPORT
MUSCLES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PEPTIDES
PHOSPHOLIPIDS
PROTEINS
RATS
REACTION KINETICS
RODENTS
RUMINANTS
SWINE
TIME DEPENDENCE
TRACER TECHNIQUES
VASOCONSTRICTORS
VERTEBRATES