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Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112
Studies were
performed to determine the responsiveness of rat juxtamedullary
afferent arterioles to receptor-selective P2-purinoceptor agonists.
Experiments were performed in vitro using the blood perfused
juxtamedullary nephron technique, combined with videomicroscopy. Renal
perfusion pressure was set at 110 mmHg and held constant. Basal
afferent arteriolar diameter averaged 22.0 ± 0.6 µm
(n = 69). Stimulation with 0.1, 1.0, 10, and 100 µM ATP (n = 10) elicited a concentration-dependent vasoconstriction averaging 8 ± 2, 17 ± 2, 21 ± 4, and 23 ± 5%, respectively. A nearly identical
afferent arteriolar vasoconstriction was observed in response to the
P2X-selective agonist
,
-methylene ATP
(n = 10); however, another P2X
agonist,
,
-methylene ATP, evoked marked receptor desensitization
(n = 10). Vessel diameter decreased by
~7 ± 2, 16 ± 2, 23 ± 3, and 22 ± 3%, respectively,
over the same concentration range. The P2Y-selective agonist,
2-methylthio-ATP, evoked only a modest vasoconstriction, whereas
UTP and adenosine
5'-O-(3-thiotriphosphate) (ATP
S) reduced afferent diameter markedly at concentrations >1.0 µM. Afferent arteriolar diameter decreased by 5 ± 4, 31 ± 8, and 72 ± 8% during UTP administration
(n = 7) at concentrations of 1.0, 10, and 100 µM, respectively. Similarly, ATP
S
(n = 6) decreased afferent
diameter by 16 ± 2, 58 ± 8, and 98 ± 3%,
respectively, over the same concentration range. Nitric oxide synthesis
inhibition with
N
-nitro-L-arginine did not
significantly alter the afferent arteriolar response to ATP but did
potentiate ATP-mediated arcuate artery vasoconstriction. The following
data suggest the presence of multiple P2 receptors on juxtamedullary
afferent arterioles and are consistent with classification of those
receptors as members of the P2X- and
P2Y2 (P2U)-receptor subtypes.
adenosine 5'-trisphosphate; uridine 5'-trisphosphate;
,
-methylene adenosine triphosphate; adenosine
5'-O-(3-thiotriphosphate); afferent arterioles; renal microcirculation
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