Adenosine-induced renal vasoconstriction in diabetes mellitus rats: role of prostaglandins

Abstract

We investigated the role of prostaglandins in the renal vascular response to exogenous and endogenous adenosine in control and streptozotocin (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 prostaglandin synthesis with indomethacin (Indo; 10 mg/kg iv) potentiated the adenosine-induced renal vasoconstriction in control rats but not in STZ rats. In control rats, Indo shifted the dose response curve of exogenous adenosine-induced RBF reductions to the left by a factor of 10 (ED50: from 5.5 ± 0.51 to 0.55 ± 0.07 nmol adenosine, n = 6, P < 0.001) and in STZ rats only by a factor of two (ED50: from 0.32 ± 0.03 to 0.16 ± 0.02 nmol adenosine, n = 6, P > 0.05). The renal response to endogenous adenosine was assessed by the magnitude of the postocclusive reduction of RBF (POR), an adenosine-mediated phenomenon. POR was greater in STZ rats (−65.3 ± 5.2%, P < 0.001) compared with control rats (−36.2 ± 3.5%). Indo markedly enhanced POR in control rats (−20.3 ± 3.7%) but not in STZ rats (−4.5 ± 2.7%). Renal cortical and medullary PGE2 microdialysate concentrations and urinary PGE2 excretions were clearly not lower in STZ (cortex: 169 ± 61 pg/ml; medulla: 640 ± 88 pg/ml, urine: 138 ± 25 pg/min) compared with control rats (cortex: 99 ± 12 pg/ml; medulla: 489 ± 107 pg/ml; urine: 82 ± 28 pg/min). Indo significantly decreased renal cortical, medullary, and urinary excretion of PGE2 in STZ and control rats. These findings demonstrate that the adenosine-induced renal vasoconstriction is increased in the presence of Indo in control rats but not in STZ rats. The observations suggest that the diabetic renal vasculature may have a diminished vasodilatory capacity in response to prostaglandins to counteract adenosine-induced renal vasoconstriction.