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Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112; and Department of Physiology, Medical College of Georgia, Augusta, Georgia 30912-3000
Experiments were performed to
determine the role of L-type calcium channels on the afferent
arteriolar vasoconstrictor response to ATP and UTP. With the use of the
blood-perfused juxtamedullary nephron technique, kidneys were perfused
at 110 mmHg and the responses of arterioles to
,
-methylene ATP,
ATP, and UTP were determined before and during calcium channel blockade
with diltiazem.
,
-Methylene ATP (1.0 µM) decreased arteriolar
diameter by 8 ± 1% under control conditions. This response was
abolished during calcium channel blockade. In contrast, 10 µM UTP
reduced afferent arteriolar diameter to a similar degree before
(20 ± 4%) and during (14 ± 4%) diltiazem treatment.
Additionally, diltiazem completely prevented the vasoconstriction normally observed with ATP concentrations below 10 µM and attenuated the response obtained with 10 µM ATP. These data demonstrate that L-type calcium channels play a significant role in the vasoconstrictor influences of
,
-methylene ATP and ATP but not UTP. The data also
suggest that other calcium influx pathways may participate in the
vasoconstrictor response evoked by P2 receptor activation. These
observations support previous findings that UTP-mediated elevation of
intracellular calcium concentration in preglomerular vascular smooth
muscle cells relies primarily on calcium release from intracellular
pools, whereas ATP-mediated responses involve both voltage-dependent
calcium influx, through L-type calcium channels, and the release of
calcium from intracellular stores. These results support the argument
that P2X and P2Y receptors influence the diameter of afferent
arterioles through activation of disparate signal transduction mechanisms.
afferent arterioles; calcium channels; cytosolic calcium; renal
microcirculation; P2X receptors; P2Y receptors; adenosine
5'-triphosphate; uridine 5'-triphosphate;
,
-methylene adenosine
5'-triphosphate; cadmium
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