Affiliation:
1. From the Cardiovascular Institute, Loyola University Chicago, Maywood, Ill.
Abstract
Abstract
[Arg
8
]-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 Ca
2+
concentration ([Ca
2+
]
i
) by releasing intracellular Ca
2+
stores and increasing Ca
2+
influx; the EC
50
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 (EC
50
≈0.05 nmol/L). The present study examined the effects of varying concentrations of AVP on spontaneous Ca
2+
spiking activity in fura 2–loaded A7r5 cells. Frequency of Ca
2+
spiking increased with increasing [AVP] in the range of 10 to 500 pmol/L. Higher concentrations of AVP inhibited spiking but elicited the characteristic [Ca
2+
]
i
changes ascribed to the release of Ca
2+
stores and increased Ca
2+
entry. The effects of both low and high concentrations of AVP were inhibited by [1-(β-mercapto-β,β,-pentamethylenepropionic acid),2-
O
-methyltyrosine]arginine vasopressin, a selective V
1a
vasopressin antagonist. Nimodipine (50 nmol/L), a blocker of L-type voltage-sensitive Ca
2+
channels, abolished the Ca
2+
-spiking activity without inhibiting a maximal [Ca
2+
]
i
response to AVP (1 μmol/L). AVP-stimulated Ca
2+
spiking, but not release of intracellular Ca
2+
stores, was also abolished by ONO-RS-082 (1 μmol/L), an inhibitor of phospholipase A
2
. These results suggest that occupation of a small fraction of V
1a
vasopressin receptors by AVP results in stimulation of phospholipase A
2
and leads to increased Ca
2+
-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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Reference22 articles.
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