RESUMEN
Oxygen consumption beyond the proximal tubule is mainly determined by active solute reabsorption, especially in the thick ascending limb of the Loop of Henle. Furosemide-induced suppression of oxygen consumption (FSOC) involves inhibition of sodium transport in this segment, which is normally accompanied by a marked decrease in the intrarenal deoxyhemoglobin detectable by blood oxygen level-dependent (BOLD)-magnetic resonance imaging (MRI). This study tested the hypothesis that the magnitude of BOLD-MRI signal change after furosemide is related to impaired renal function in renovascular hypertension. In 16 pigs with unilateral renal artery stenosis, renal hemodynamics, function, and tubular function (FSOC and fluid concentration capacity) were evaluated in both kidneys using MR and multidetector computerized tomography (MDCT) imaging. Animals with adequate FSOC (23.6 +/- 2.2%, P > 0.05 vs. baseline) exhibited a mean arterial pressure (MAP) of 113 +/- 7 mmHg, and relatively preserved glomerular filtration rate (GFR) of 60 +/- 4.5 ml/min, comparable to their contralateral kidney (66 +/- 4 ml/min, P > 0.05). In contrast, animals with low FSOC (3.1 +/- 2.1%, P = NS vs. baseline) had MAP of 124 +/- 9 mmHg and GFR (22 +/- 6 ml/min) significantly lower than the contralateral kidneys (66 +/- 4 ml/min, P < 0.05). The group with preserved GFR and FSOC showed an increase in intratubular fluid concentration as assessed by MDCT that was greater than that observed in the low GFR group, suggesting better preservation of tubular function in the former group. These results suggest that changes in BOLD-MRI after furosemide can differentiate between underperfused kidneys with preserved tubular function and those with tubular dysfunction. This approach may allow more detailed physiologic evaluation of poststenotic kidneys in renovascular hypertension than previously possible.
Asunto(s)
Hipertensión Renovascular/fisiopatología , Hipoxia/fisiopatología , Médula Renal/fisiopatología , Consumo de Oxígeno , Animales , Diuréticos , Femenino , Furosemida , Tasa de Filtración Glomerular , Hipertensión Renovascular/metabolismo , Hipoxia/metabolismo , Médula Renal/metabolismo , Túbulos Renales/metabolismo , Túbulos Renales/fisiopatología , Imagen por Resonancia Magnética , Oxígeno/sangre , Circulación Renal , PorcinosRESUMEN
The controversy over beneficial versus harmful effects of salt on cardiovascular outcomes may be caused by different effects of salt on intermediate phenotypes of hypertension not characterized in epidemiological studies. Hence, we investigated acute effects of salt on oxidative stress in hypertensive subjects classified as salt sensitive (SS, n=14) or salt resistant (SR, n=13) by an inpatient protocol of salt loading (460 mmol NaCl) and salt depletion (10 mmol NaCl and furosemide). Oxidative stress was assessed by measuring the plasma isoprostane 8-iso-PGF2alpha. SS had lower plasma renin activity, higher aldosterone/renin ratios, and exaggerated endothelin and catecholamine responses to salt depletion compared with SR. Baseline lipid-bound isoprostanes (749+/-70 pmol/L) were 83% of the total and were slightly but not significantly higher in SS than SR. Baseline free isoprostanes did not differ between groups. After salt loading, lipid-bound isoprostanes were higher in SS (945+/-106) than SR (579+/-57; P<0.01). Salt depletion significantly decreased them in SS (-174+/-84) and increased them in SR (+129+/-58), equalizing their levels (771+/-61 versus 708+/-91; P value not significant). Free isoprostanes were decreased by salt depletion only if data in all of the patients were analyzed together. Total isoprostanes followed the pattern of the lipid-bound fraction. Correlations between salt depletion-induced changes in lipid-bound isoprostanes, plasma renin activity (r=0.45; P<0.02), and aldosterone/renin ratios (r=-0.41; P<0.04) suggested that the more SS the patient, the greater the reduction of oxidative stress by salt depletion. Our research is the first to show that salt affects oxidative stress acutely in humans, particularly in SS hypertension, which may explain the controversial results of epidemiological studies on salt and morbidity and may have implications for therapy.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Hipertensión/fisiopatología , Isoprostanos/sangre , Estrés Oxidativo/efectos de los fármacos , Cloruro de Sodio/farmacología , Adulto , Biomarcadores/sangre , Dinoprost/análogos & derivados , Dinoprost/sangre , Diuréticos/farmacología , Resistencia a Medicamentos , Femenino , Furosemida/farmacología , Humanos , Hipertensión/sangre , Hipertensión/metabolismo , Masculino , Persona de Mediana Edad , Cloruro de Sodio/metabolismoRESUMEN
There is substantial evidence suggesting that angiotensin II plays an important role in elevating blood pressure of spontaneously hypertensive rats, despite normal plasma renin activity, and that converting enzyme inhibitors (captopril) can effectively normalize blood pressure in the spontaneously hypertensive rats. One mechanism by which angiotensin II induces hypertension is via oxidative stress and endothelin, as seen in subpressor angiotensin II-induced hypertension. In fact, it has been shown that antioxidants lower mean arterial pressure in spontaneously hypertensive rats. However, the relationship between angiotensin II, oxidative stress, and endothelin in the spontaneously hypertensive rats is still relatively undefined. This study examines the relationship between mean arterial pressure, plasma renin activity, angiotensin II, oxidative stress, and endothelin in spontaneously hypertensive rats compared with normotensive Wistar Kyoto rats, and the effects of captopril on this association. Untreated spontaneously hypertensive rats had increased plasma angiotensin II levels despite normal plasma renin activity, oxidative stress, and endothelin. Captopril treatment in spontaneously hypertensive rats lowered mean arterial pressure, angiotensin II, oxidative stress, and endothelin, and increased plasma renin activity. In contrast, captopril increased plasma renin activity (suggesting effective captopril treatment) but did not significantly alter mean arterial pressure, angiotensin II, oxidative stress, or endothelin of Wistar Kyoto rats. These results suggest that in spontaneously hypertensive rats, angiotensin II is a primary instigator of hypertension, and that captopril selectively lowers angiotensin II, oxidant stress, and endothelin, which in turn may contribute to the blood pressure-lowering efficacy of captopril in spontaneously hypertensive rats.