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Contrast-induced nephropathy is a common cause of acute renal failure, and the mechanisms underlying this injury are not completely understood. We sought to determine how physicochemical properties of contrast media may contribute to kidney damage in rats. We administered contrast media of equivalent iodine concentrations but differing physiocochemical properties: the high-osmolality iopromide was compared to the high-viscosity iodixanol. In addition, the non-iodinated substances mannitol (equivalent osmolality to iopromide) and dextran (equivalent viscosity to iodixanol) were also studied. Both types of contrast media transiently increased renal and hindquarter blood flow. The high-osmolality agents iopromide and mannitol markedly increased urine production whereas iodixanol, which caused less diuresis, significantly enhanced urine viscosity. Only the high-viscosity agents iodixanol and dextran decreased renal medullary blood flux, erythrocyte concentration, and pO2. Moreover, iodixanol prolonged the tubuloglomerular feedback response and increased plasma creatinine levels to a greater extent than iopromide or dextran. Therefore, the viscosity of contrast media may play a significant role in contrast-induced nephropathy.

Response of renal vasculature to changes in renal perfusion pressure (RPP) involves mechanisms with different frequency characteristics. Autoregulation of renal blood flow is mediated by a rapid myogenic response and a slower tubuloglomerular feedback mechanism. In 25 male conscious rats, ramp-shaped changes in RPP were induced to quantify dynamic properties of autoregulation. Decremental RPP ramps immediately followed by incremental ramps were made for four different rates of change, ranging from 0.118 to 1.056 mmHg/s. Renal blood flow and cortical and medullary fluxes were assessed, and the corresponding relative conductance values were calculated continuously. During RPP decrements, conductance increased. With increasing rate of change of RPP decrements, maximum conductance increased from 10% to 80%, as compared with control. This response, which indicates the magnitude of autoregulation, was more pronounced in cortical versus medullary vasculature. Pressure at maximum conductance decreased with increasing rate of change of RPP decrements from 88 to 72 mmHg. During RPP increments, dependence of maximum conductance changes on the rate of change was enhanced (-20 to 110% of control). Thus, a hysteresis-like asymmetry between RPP decrements and increments, a resetting of autoregulation, was observed, which in direction and magnitude depended on the rate of change and duration of RPP changes. In conclusion, renal vascular responses to changes in RPP are highly dependent on the dynamics of the error signal. Furthermore, the method presented allows differentiated stimulation of various static and dynamic components of pressure-flow relationship and, thus, a direct assessment of the magnitudes and operating pressure range of active mechanisms of pressure-flow relationships.

Nitric oxide modulates renal hemodynamics and salt and water handling. Studies on the latter have provided conflicting results, however. Electrolyte and water balances were therefore studied in 28 beagles for 4 d, to determine the various effects of nitric oxide synthase (NOS) inhibition on renal function. The dogs were chronically equipped with aortic occluders to reduce renal perfusion pressure (RPP), bladder catheters, and catheters for measurements of RPP and mean arterial BP. A swivel system allowed free movement within the kennels. In a first set of experiments, a nonpressor dose of L-Nomega-nitroarginine (LN) (3 microg/min per kg body wt) was administered, to prevent increases in mean arterial BP and thus pressure effects on renin release and natriuresis. Remarkably, the nonpressor dose of LN caused a negative sodium balance. The natriuretic effect may involve reduced plasma renin activity, reduced aldosterone concentrations, and increased atrial natriuretic peptide concentrations. Changes in aldosterone levels, however, were the only parameters to parallel the time course of sodium excretion. In a second set of experiments, a sodium-retaining challenge was elicited by reduction of RPP. Dogs without NOS inhibition escaped sodium retention during RPP reduction after 2 d ("pressure escape"). LN neither ameliorated nor aggravated the sodium-retaining effect of reduced RPP, nor did it compromise the accomplishment of pressure escape. In conclusion, inhibition of NOS with a low dose of LN results in a reduction of total-body sodium. This effect mainly relies on reduced aldosterone concentrations. Furthermore, LN does not change the regulatory response to long-term RPP reduction.

Previous studies have suggested a link between renal metabolism and local kidney hemodynamics to prevent potential hypoxic injury of particularly vulnerable nephron segments, such as the outer medullary region. The present study used three different inspiratory oxygen concentrations to modify renal metabolic state in the conscious rat (hypoxia 10% O2, normoxia 20% 02, and hyperoxia 100% 02). Renal blood flow (RBF) was assessed by ultrasound transit time; renal perfusion pressure (RPP) was controlled by a hydroelectric servo-control device. Local RBF was estimated by laser-Doppler flux for the cortical and outer medullary region (2 and 4 mm below renal surface, respectively). Hypoxia led to a generalized significant increase in RBF, whereas hyperoxia-induced changes did not (hypoxia 6.6 +/- 0.6 ml/min versus normoxia 5.7 +/- 0.7 ml/min, P < 0.05). Moreover, regional and total RBF autoregulation was markedly attenuated by hypoxia. Conversely, hyperoxia enhanced RBF autoregulation. Under normoxic and hyperoxic conditions, medullary RBF was very well maintained, even at low RPP (medullary RBF: approximately 70% of control at 50 mmHg). The hypoxic challenge, however, significantly diminished the capacity to maintain medullary blood flow at low RPP (medullary RBF: approximately 30% of control at 50 mmHg, P < 0.05). These data suggest that renal metabolism and renal hemodynamics are closely intertwined. In response to acute hypoperfusion, the kidney succeeds in maintaining remarkably high medullary blood flow. This is not accomplished, however, when a concomitant hypoxic challenge is superimposed on RPP reduction.