Pflueger, Axel

The role of nitric oxide (NO) in the regulation of the intrarenal microcirculation in streptozotocin (STZ)-induced diabetes mellitus in rats is not clear. We examined renal cortical and papillary hemodynamics in STZ rats and determined the effects of systemic inhibition and stimulation of NO synthesis. Renal blood flow in cortical (QCC), and inner medullary ascending (QAV) and descending (QDV) vasa recta capillaries was measured by fluorescence videomicroscopy in STZ Munich-Wistar rats and nondiabetic control rats. Ten days after STZ injection (80 mg/kg ip), basal QCCand QDVwere significantly greater in STZ rats ( n = 16) compared with control rats ( n = 15). Infusion of NG-monomethyl-l-arginine (l-NMMA, 15 mg/kg bolus, 500 μg ⋅ min−1⋅ kg−1iv) decreased QCC(−41%), QAV(−38%), and QDV(−37%) in control rats ( n = 6) and to a significantly greater magnitude than in STZ rats ( n = 7), QCC(−14%), QAV(−20%), and QDV(−25%). Coinfusion ofl-arginine (l-Arg, 1 mg ⋅ kg−1⋅ min−1iv) with l-NMMA increased QCCto a significantly greater extent ( P < 0.01) in control rats compared with STZ rats. In subsequent studies, infusion ofl-Arg alone increased QCC(+50%), QAV(+16%), and QDV(+11%) in control rats ( n = 5) but had no effect in STZ rats ( n = 5). These results show that the response of renal cortical and papillary capillary blood flow to both inhibition and stimulation of NO synthesis is attenuated in the early onset of STZ-diabetes mellitus rats compared with control rats.

We previously demonstrated an increased sensitivity of the renal vasculature to adenosine (ADO) mediated via ADO A1receptors in streptozotocin (STZ) diabetic rats. Because ADO stimulates Pireabsorption in the proximal tubule, the present study was performed to determine whether the sensitivity of the renal tubular system to the antiphosphaturic effect of ADO is enhanced in STZ rats. Clearance studies were performed, and ADO was infused into the renal interstitium via implanted matrices in STZ- and control (Con) rats to mimic the effects of endogenous ADO. Renal phosphate excretion was significantly increased in STZ rats (0.75 ± 0.05 μmol/24 h) compared with Con rats (0.35 ± 0.08 μmol/24 h), and fractional phosphate excretion ([Formula: see text]) tended to be higher in STZ rats (34.8 ± 4.1%) than in Con rats (26.7 ± 2.2%). Renal interstitial ADO infusion (5 μmol/h) was significantly more antiphosphaturic in STZ rats ([Formula: see text] decreased by 6.95 ± 1.36%; P < 0.05) than in Con rats ([Formula: see text] decreased by 2.90 ± 1.6%; P > 0.05), in which ADO only tended to decrease[Formula: see text]. To determine the role of ADO A1receptors on Piexcretion, the selective ADO A1receptor blocker 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was infused into the renal interstitium. DPCPX increased[Formula: see text] by 4.3 ± 1.2% ( P < 0.05) in the presence and 7.1 ± 3.9% ( P < 0.05) in the absence of ADO infusion in Con rats but had no effect on[Formula: see text] in STZ rats. In conclusion, STZ-diabetes mellitus enhances the antiphosphaturic effect of ADO by mechanisms unrelated to ADO A1receptor stimulation.

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 PGE2microdialysate concentrations and urinary PGE2excretions 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 PGE2in 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.

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 Nω-nitro-l-arginine (l-NNA, 30 μmol/kg iv) and with renal perfusion pressure controlled potentiated the adenosine-induced renal vasoconstriction to a significantly greater extent in control rats than in 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 [half-maximal effective dose (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-s renal artery occlusion. POR was markedly enhanced in STZ rats (−67.8 ± 3.8%, P < 0.001) compared with 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 ofl-NNA infusion in control rats compared with 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.

Purpose: To compare the clinical outcomes in patients with chronic renal insufficiency (CRI) and renal artery stenosis (RAS) following renal artery (RA) stent placement with and without embolic protection device (EPD) usage. Materials and Methods: Eighteen patients who had RA stent placement with EPD were matched to control patients (RA stent only). Blood pressure, number of hypertensive medications, and estimated glomerular filtration rate (eGFR) at 3 months before the procedure and after 12 months were determined. An increase of ≥ 20% in eGFR at 12 months from baseline was defined as “improvement,” decrease of ≥20% as “deterioration,” and an eGFR change between those values as “stabilization” at 12 months. Results: At 12 months, stage 4 patients treated with EPD had significantly higher eGFR than controls ( P = .01). There was no statistical difference in blood pressure outcomes between the 2 groups. Conclusions: Patients with stage 4 CRI did significantly better with EPD than those treated without it.