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(Circulation Research. 1996;78:813-820.)
© 1996 American Heart Association, Inc.

Articles

Vasopressin Stimulates Ca²⁺ Spiking Activity in A7r5 Vascular Smooth Muscle Cells via Activation of Phospholipase A₂

Kenneth L. Byron

From the Cardiovascular Institute, Loyola University Chicago, Maywood, Ill.

Correspondence to Dr Kenneth L. Byron, Loyola University Medical Center, Cardiovascular Institute, 2160 S First Ave, Bldg 110, Room 5221, Maywood, IL 60153. E-mail kbyron@orion.it.luc.edu.

Abstract [Arg⁸]-vasopressin (AVP) is both a potent vasoconstrictor and a mitogen for vascular smooth muscle cells. AVP binds to a single class of receptors (V_1a) in the A7r5 rat aortic smooth muscle cell line (K_d 2 nmol/L). Stimulation of these cells with AVP results in an increase in cytoplasmic free Ca²⁺ concentration ([Ca²⁺]_i) by releasing intracellular Ca²⁺ stores and increasing Ca²⁺ influx; the EC₅₀ for these effects is 5 nmol/L. AVP has recently been reported to stimulate arachidonic acid release in primary cultures of rat aortic smooth muscle over a much lower concentration range (EC₅₀ 0.05 nmol/L). The present study examined the effects of varying concentrations of AVP on spontaneous Ca²⁺ spiking activity in fura 2–loaded A7r5 cells. Frequency of Ca²⁺ spiking increased with increasing [AVP] in the range of 10 to 500 pmol/L. Higher concentrations of AVP inhibited spiking but elicited the characteristic [Ca²⁺]_i changes ascribed to the release of Ca²⁺ stores and increased Ca²⁺ entry. The effects of both low and high concentrations of AVP were inhibited by [1-(ß-mercapto-ß,ß,-pentamethylenepropionic acid),2-O-methyltyrosine]arginine vasopressin, a selective V_1a vasopressin antagonist. Nimodipine (50 nmol/L), a blocker of L-type voltage-sensitive Ca²⁺ channels, abolished the Ca²⁺-spiking activity without inhibiting a maximal [Ca²⁺]_i response to AVP (1 µmol/L). AVP-stimulated Ca²⁺ spiking, but not release of intracellular Ca²⁺ stores, was also abolished by ONO-RS-082 (1 µmol/L), an inhibitor of phospholipase A₂. These results suggest that occupation of a small fraction of V_1a vasopressin receptors by AVP results in stimulation of phospholipase A₂ and leads to increased Ca²⁺-spiking activity. This effect may be important for fine tuning of vascular tone, whereas maximal stimulation by AVP (full receptor occupancy) may be required for more vigorous or sustained vasoconstriction or mitogenesis.

Key Words: vasopressin • vascular smooth muscle • phospholipase A₂ • intracellular Ca²⁺

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