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 (ED(50): 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 (ED(50): 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 PGE(2) microdialysate concentrations and urinary PGE(2) 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 PGE(2) 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.