Adenosine-induced renal vasoconstriction in diabetes mellitus rats:
role of nitric oxide.
Pflueger, Axel C., Hartmut Osswald and Franklyn G. Knox.
Departments of Medicine and Physiology & Biophysics, Mayo Clinic
and Foundation, Rochester, MN 55905 and *Department of Pharmacology,
Faculty of Medicine, Tuebingen University, 72074 Tuebingen,
Germany
APStracts 5:0213F, 1998.
In rats with streptozotocin (STZ)-induced diabetes, the renal
vasoconstrictor effect of adenosine is enhanced. We investigated the
role of nitric oxide (NO) in the renal vascular response to exogenous
and endogenous adenosine in control and STZ diabetic rats. Exogenous
adenosine (0.01-100 nmol) injected into the abdominal aorta,
decreased renal blood flow (RBF) in a dose-dependent manner to a much
greater extent in STZ rats than in control rats (P<0.001).
Inhibition of NO synthesis with N-(-nitro-L-arginine (L-NNA, 30
_mol/kg i.v.) and with renal perfusion pressure controlled
potentiated the adenosine-induced renal vasoconstriction to a
significantly greater extent in control rats than STZ rats. In
control rats, L-NNA shifted the dose response curve of exogenous
adenosine-induced RBF reductions to the left by a factor of 32 (ED50:
from 5.5 to 0.17 nmol adenosine, n=6) and in STZ rats only by a
factor of 4.6 (ED50: from 0.32 to 0.07 nmol adenosine, n=6). The
renal response to endogenous adenosine was assessed by the magnitude
of the postocclusive reduction of RBF (POR) after a 30 sec renal
artery occulusion. POR was markedly enhanced in STZ rats (-67.8(3.8
%, P<0.001) compared to control rats (-38.8(4.3 %). L-NNA markedly
enhanced POR in control rats but did not increase POR in STZ rats.
These findings demonstrate a greater potentiation of the adenosine
-induced renal vasoconstriction in the presence of L-NNA infusion in
control rats compared to STZ rats. We conclude that the increased
vasoconstrictor sensitivity of the diabetic renal vasculature to
adenosine is caused by a defective NO-dependent renal vasodilation of
the afferent arteriole in diabetic rats.
Received 29 September 1998; accepted in final form 10 December
1998.
APS Manuscript Number F253-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 18 December 1998