Direct assessment of renal microvascular responses to p2
purinoceptor agonists.
Inscho, Edward W., Anthony K. Cook, Vy Mui, and Jason Miller.
Department of Physiology, Tulane University School of Medicine, New
Orleans, LA 70112
APStracts 5:0005F, 1998.
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 _m (n=69). Stimulation with 0.1, 1.0, 10 and 100 _M 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 [beta], _-methylene ATP (n=10); however,
another P2X agonist, [alpha], [beta]-methylene ATP, evoked marked
receptor desensitization (n=10). Vessel diameter decreased by
approximately 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 ATP-_-S, reduced afferent diameter markedly at
concentrations above 1.0 _M. 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 _M; 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.
Received 10 July 1997; accepted in final form 5 January 1998.
APS Manuscript Number F227-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 28 January 1998