Renal Arterial Pressure Research Articles

Chronic responses of renal and lumbar sympathetic nerve activity and arterial pressure to sino-aortic baroreceptor denervation in rats

Chronic responses of renal and lumbar sympathetic nerve activity and arterial pressure to sino-aortic baroreceptor denervation in rats

Percutaneous Embolization of Iatrogenic Arterial Kidney Injuries: Safety, Efficacy, and Impact on Blood Pressure and Renal Function

Purpose To evaluate the efficacy and safety of percutaneous renal artery embolization (RAE) of iatrogenic vascular kidney injuries and the effects of RAE on renal function and arterial blood pressure (BP). Materials and Methods Over a 12-year period, 50 consecutive patients with severe hemorrhage after iatrogenic arterial kidney injuries underwent RAE. Technical success was defined as occlusion of the bleeding site, and clinical success was defined as complete bleeding cessation. The effects on renal function and arterial BP were assessed by comparing the estimated glomerular filtration rate (eGFR), renal function stage (National Kidney Foundation scale), systolic BP, and BP stage (European Society of Hypertension classification) before and after RAE. Results RAE was technically successful in 49 patients (98%). Two patients were lost to follow-up after RAE. Clinical success was obtained in 40 (83%), 45 (94%), and 47 patients (98%), respectively, at 24, 48, and 96 hours after RAE. Three patients (6%) had minor complications, and one patient (2%) died within 30 days after RAE. Follow-up renal function data (mean, 4 mo) were available for 33 patients (66%). No statistically significant differences in eGFR ( P = .186) or renal function stage ( P = .183) were apparent after RAE. Follow-up BP data (mean, 3 mo) were available for 28 patients (56%). There were no significant differences in systolic BP ( P = .233) or BP stage ( P = .745) after RAE. Conclusions Embolization of iatrogenic renal artery injuries is safe and associated with high technical and clinical success rates. It is not associated with a significant worsening of renal function or increase in BP.

Inhibition of soluble epoxide hydrolase improves the impaired pressure–natriuresis relationship and attenuates the development of hypertension and hypertension-associated end-organ damage in Cyp1a1-Ren-2 transgenic rats

In the present study, we compared the effects of treatment with the novel soluble epoxide hydrolase (sEH) inhibitor (c-AUCB) with those of the AT1 receptor antagonist losartan on blood pressure (BP), autoregulation of renal blood flow (RBF) and on glomerular filtration rate (GFR) and the pressure-natriuresis relationship in response to stepwise reduction in renal arterial pressure (RAP) in Cyp1a1-Ren-2 transgenic rats. Hypertension was induced in Cyp1a1-Ren-2 rats through dietary administration for 11 days of the natural xenobiotic indole-3-carbinol (I3C) which activates the renin gene. Treatment with c-AUCB and losartan was started 48 h before initiating administration of the diet containing I3C. Rats were prepared for renal functional studies to evaluate in-vivo renal autoregulatory efficiency when RAP was gradually decreased by an aortic clamp. I3C administration resulted in the development of severe hypertension which was associated with markedly lower basal RBF and GFR and substantially impaired autoregulatory efficiency as well as a suppression of the pressure-natriuresis relationship when compared with noninduced rats. Treatment with c-AUCB significantly decreased BP, improved autoregulatory efficiency of RBF and GFR and the slope of pressure-natriuresis relationship. Treatment with losartan completely prevented the impaired autoregulation and pressure-natriuresis relationship as well as the development of hypertension in I3C-induced rats. Our present findings indicate that chronic treatment with the sEH inhibitor c-AUCB substantially attenuates the development of malignant hypertension in I3C-induced rats likely via improvement of the renal autoregulatory efficiency and the pressure-natriuresis relationship.

Intravenous Sildenafil as a Preconditioning Drug Against Hemodynamic Consequences of Warm Ischemia-Reperfusion on the Kidney

We designed an experimental model of renal ischemia-reperfusion to evaluate the preemptive effect of intravenous sildenafil according to the dose administered (0.7 vs 1.4 mg/kg) and the time of administration (30 minutes before ischemia or during ischemia). A total of 20 minipigs were divided into groups of 4 each, including group 1-control, group 2-sildenafil 0.7 mg/kg intravenously 30 minutes before vascular clamping, group 3-sildenafil 0.7 mg/kg intravenously during warm ischemia, group 4-sildenafil 1.4 mg/kg intravenously 30 minutes before vascular clamping and group 5-sildenafil 1.4 mg/kg intravenously during warm ischemia. The ischemia-reperfusion model was applied using laparotomy and right kidney vascular clamping for 30 minutes, followed by unclamping and reperfusion for 45 minutes. Renal vascular flow and systemic mean arterial pressure were recorded for 45 minutes after unclamping. Mean values were compared using Student t test with significance considered at p <0.05. Sildenafil led to a decrease in arterial pressure compared to that in controls, especially at the dose of 1.4 vs 0.7 mg/kg, including 113.77, 109.76, 106.12, 97.41 and 82.85 mm Hg in groups 1 to 5, respectively. Renal vascular flow was significantly higher in groups 2 and 3 than in groups 1, 4 and 5 (112.82 and 111.33 vs 88.25, 87.91 and 84.37 ml per minute, respectively, p = 0.000). The effect of intravenous sildenafil as a preemptive drug against the hemodynamic effects of renal ischemia-reperfusion is dose dependent. The 0.7 mg/kg dose significantly increased reperfusion renal vascular flow with a small decrease in arterial pressure compared to the 1.4 mg/kg dose.

Role of cytochromeP-450 metabolites in the regulation of renal function and blood pressure in 2-kidney 1-clip hypertensive rats

Alterations in renal function contribute to Goldblatt two-kidney, one-clip (2K1C) hypertension. A previous study indicated that bioavailability of cytochrome P-450 metabolites epoxyeicosatrienoic acids (EETs) is decreased while that of 20-hydroxyeicosatetraenoic acids (20-HETE) is increased in this model. We utilized the inhibitor of soluble epoxide hydrolase cis-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (c-AUCB) and HET-0016, the inhibitor of 20-HETE production, to study the role of EETs and 20-HETE in the regulation of renal function. Chronic c-AUCB treatment significantly decreased systolic blood pressure (SBP) (133 ± 1 vs. 163 ± 3 mmHg) and increased sodium excretion (1.23 ± 0.10 vs. 0.59 ± 0.03 mmol/day) in 2K1C rats. HET-0016 did not affect SBP and sodium excretion. In acute experiments, renal blood flow (RBF) was decreased in 2K1C rats (5.0 ± 0.2 vs. 6.9 ± 0.2 ml·min(-1)·g(-1)). c-AUCB normalized RBF in 2K1C rats (6.5 ± 0.6 ml·min(-1)·g(-1)). HET-0016 also increased RBF in 2K1C rats (5.8 ± 0.2 ml·min(-1)·g(-1)). Although RBF and glomerular filtration rate (GFR) remained stable in normotensive rats during renal arterial pressure (RAP) reductions, both were significantly reduced at 100 mmHg RAP in 2K1C rats. c-AUCB did not improve autoregulation but increased RBF at all RAPs and shifted the pressure-natriuresis curve to the left. HET-0016-treated 2K1C rats exhibited impaired autoregulation of RBF and GFR. Our data indicate that c-AUCB displays antihypertensive properties in 2K1C hypertension that are mediated by an improvement of RBF and pressure natriuresis. While HET-0016 enhanced RBF, its anti-natriuretic effect likely prevented it from producing a blood pressure-lowering effect in the 2K1C model.

Cardiovascular and Sympathetic Effects of Disrupting Tyrosine 985 of the Leptin Receptor

Leptin acts in the brain to regulate food intake and energy expenditure. Leptin also increases renal sympathetic nerve activity and arterial pressure. The divergent signaling capacities of the leptin receptor (ObRb) mediate the stimulation of various intracellular pathways that are important for leptin control of physiological processes. We evaluated the cardiovascular and sympathetic consequences of disrupting the signal emanating from tyrosine985 of ObRb. For this, we used Lepr(L985) (l/l) mice, which carry a loss of function mutation replacing tyrosine985 of ObRb with leucine. Body weight of l/l mice was not significantly different from wild-type controls. In contrast, radiotelemetry measurements revealed that the l/l mice had higher arterial pressure and heart rate as compared with controls. Ganglionic blockade caused a greater arterial pressure fall in the l/l mice relative to controls. In addition, leptin treatment induced a larger increase in arterial pressure and heart rate in the l/l versus wild-type mice. Finally, we compared the response of renal and brown adipose tissue sympathetic nerve activity to intracerebroventricular injection of leptin (2 μg) between l/l and control mice. Leptin-induced increase in renal sympathetic nerve activity was greater in l/l mice relative to controls. In contrast, the brown adipose tissue sympathetic nerve activity response to leptin was attenuated in the l/l mice relative to controls. These data indicate that selective loss of leptin receptor signaling emanating from tyrosine985 enhances the cardiovascular and renal sympathetic effects of leptin. These findings provide important insight into the molecular mechanisms underlying leptin's effects on the sympathetic cardiovascular function and arterial pressure.

Relationship between the decline of age-related renal function and central aortic pressure in healthy Uygur population

To study the relationship between the decline of age-related renal function and central arterial pressure (CAP) in Uygur healthy population. A total of 638 healthy Uygur inhabitants from Hetian region, Xinjiang province were enrolled. They were divided into 4 groups according to their ages. Their blood pressure, serum creatinine and other indicators were detected. eGFR (estimated glomerular filtration rate) was calculated by the formula of Chinese-based MDRD (Modification of Diet in Renal Disease). CAP was measured by a pulse wave analyzer including central arterial systolic blood pressure (C-SBP), central arterial pulse pressure (C-PP), augmentation pressure (AP), augmentation index (AIX) and other components. CAP and brachial arterial pressure tended to increase and renal function declined with age. There were gender differences in renal function. Both AP and AIX changed with age (P < 0.05). In each group, AP and AIX increased even more significantly in females (P < 0.01). The average age of subjects with a high AIX was 52 y ± 12 y. And it was elder than that of those with a low AIX (44 y ± 13 y, P = 0.000). The renal function of those with a high AIX was lower than those with a low AIX [(121 ± 25) ml.min. (1.73 m(2))(-1)] vs (131 ± 33) ml.min. (1.73 m(2))(-1), P = 0.000]. The levels of C-PP and AP were much higher in those with a high AIX (P = 0.00). The results of multivariate analysis showed that eGFR was negatively correlated with the level of AIX (P < 0.01). And it had no relationship with the brachial artery pressure (P > 0.05). Central arterial pressure is associated with the decline of age-related renal function. Monitoring of CAP may help to screen the high-risk patients in the elderly population. This study provides rationales for new therapeutics of protecting the aging of kidneys.

Infrarenal aortic‐clamping after renal ischaemia aggravates acute renal failure

Renal failure is a frequent complication of juxtarenal abdominal aortic aneurysm (JAA)-repair. During this operation, suprarenal aortic-clamping is followed by infrarenal aortic-clamping (below renal arteries) to restore renal flow, while performing the distal anastomosis. We hypothesized that infrarenal aortic-clamping, despite restoring renal perfusion provokes additional renal damage. We studied three groups of rats. After 45min of suprarenal aortic-clamping, group 1 had renal reperfusion for 90min without aortic-clamps (n=7). In group 2, 45min of suprarenal aortic-clamping with a distal clamp on the aortic-bifurcation was followed by 20min of infrarenal aortic-clamping. Renal reperfusion was continued for 70min without aortic-clamps (i.e. 90 min of renal reperfusion; n=8). The sham-group had no clamps (n=7). We measured renal haemodynamics, functional parameters and tissue damage. On suprarenal aortic-clamp removal, renal artery flow, cortical flow and arterial pressures were higher in group 2 than in group 1. We detected increased tubular brush border damage, luminal lipocalin-2 and 30-60% higher renal protein nitrosylation in group 2 when compared to group 1 (P<0·05). Group 2 showed more release of asymmetrical dimethylarginine (ADMA) from the kidneys in the renal vein, therefore indicating diminished clearing capacity (P<0·001). Arginine/ADMA-ratio, which defines the bio-availability of nitric oxide, tended to be lower in group 2 and correlated with renal flow. Furthermore, there were no significant differences found in creatinine levels and renal leucocyte accumulation between group 1 and 2. Additional infrarenal aortic-clamping leads to increased renal damage and oxidative stress, despite adequate perfusion of kidneys after suprarenal aortic-clamping. This study indicates that the clamping sequence used in JAA-repair causes more than simple renal I/R-injury.

Enhanced angiotensin II-mediated central sympathoexcitation in streptozotocin-induced diabetes: role of superoxide anion

Studies have shown that the superoxide mechanism is involved in angiotensin II (ANG II) signaling in the central nervous system. We hypothesized that ANG II activates sympathetic outflow by stimulation of superoxide anion in the paraventricular nucleus (PVN) of streptozotocin (STZ)-induced diabetic rats. In α-chloralose- and urethane-anesthetized rats, microinjection of ANG II into the PVN (50, 100, and 200 pmol) produced dose-dependent increases in renal sympathetic nerve activity (RSNA), arterial pressure (AP), and heart rate (HR) in control and STZ-induced diabetic rats. There was a potentiation of the increase in RSNA (35.0 ± 5.0 vs. 23.0 ± 4.3%, P < 0.05), AP, and HR due to ANG II type I (AT(1)) receptor activation in diabetic rats compared with control rats. Blocking endogenous AT(1) receptors within the PVN with AT(1) receptor antagonist losartan produced significantly greater decreases in RSNA, AP, and HR in diabetic rats compared with control rats. Concomitantly, there were significant increases in mRNA and protein expression of AT(1) receptor with increased superoxide levels and expression of NAD(P)H oxidase subunits p22(phox), p47(phox), and p67(phox) in the PVN of rats with diabetes. Pretreatment with losartan (10 mg·kg(-1)·day(-1) in drinking water for 3 wk) significantly reduced protein expression of NAD(P)H oxidase subunits (p22(phox) and p47(phox)) in the PVN of diabetic rats. Pretreatment with adenoviral vector-mediated overexpression of human cytoplasmic superoxide dismutase (AdCuZnSOD) within the PVN attenuated the increased central responses to ANG II in diabetes (RSNA: 20.4 ± 0.7 vs. 27.7 ± 2.1%, n = 6, P < 0.05). These data support the concept that superoxide anion contributes to an enhanced ANG II-mediated signaling in the PVN involved with the exaggerated sympathoexcitation in diabetes.

E0658 Establishment of York pig model of acute myocardial infarction with acute decompensated heart failure by coronary occlusion with balloon and injecting of microembolus

ObjectiveTo evaluate the method of yorkpig model of AMI-ADHF by coronary occlusion with balloon and injecting of microembolus and evaluate the change of coronary and renal haemodynamic parameters on York...

E0656 The effect of recombinant human B-type natriuretic peptid on coronary circulation and renal haemodynamics in York pigs model of acute myocardial infarction with heart failure

ObjectiveTo evaluate the impact of intravenous administration of rhBNP on coronary and renal artery haemodynamics in York pigs model of AMI-ADHF.Methods14 York pigs were included in this study. After the...

E0626 The effects of recombinant human B-type natriuretic peptid on coronary circulation and renal haemodynamics in York pigs model of acute myocardial infarction with heart failure

ObjectiveTo evaluate the impact of intravenous administration of rhBNP on coronary and renal artery haemodynamics in York pigs model of AMI-ADHF.MethodsFourteen York pigs were included in this study. After the...

Femoral artery occlusion increases expression of ASIC3 in dorsal root ganglion neurons

Acid-sensing ion channels (ASICs) in sensory nerves are responsive to increases in the levels of protons in the extracellular medium. Prior studies suggest that the muscle metabolite, lactic acid, plays a role in reflex sympathetic and cardiovascular responses via stimulation of thin muscle afferent nerves. Also, femoral artery occlusion augments the reflex sympathetic nerve response in rats. ASIC3 is a main subtype to appear in sensory nerves in mediating the response induced by increases in protons in the interstitial space of contracting muscles. Thus, in this article, we hypothesized that femoral occlusion increases the expression of ASIC3 in primary afferent neurons innervating muscles, and this contributes to the exaggerated reflex sympathetic responses. Femoral occlusion/vascular insufficiency of the hindlimb muscles was induced by the femoral artery ligation in rats. First, Western blot analysis shows that 24-72 h of femoral artery ligation significantly increased the expression of ASIC3 protein in dorsal root ganglion (optical density, 1.0 ± 0.07 in control vs. 1.65 ± 0.1 after 24 h of occlusion, P < 0.05; n = 6 in each group). There were no significant differences for increases in ASIC3 24 and 72 h postocclusion. Second, experiments using fluorescent immunohistochemistry and retrograde-labeling technique show that a greater percentage of ASIC3 staining neurons are localized in muscle-innervating dorsal root ganglion neurons after the arterial occlusion (78 ± 3% in 24 h post occlusion vs. 59 ± 5% in control, P < 0.05; n = 6 in each group). Third, the reflex responses in renal sympathetic nerve and arterial blood pressure induced by the stimulation of ASIC were examined after an injection of lactic acid into the arterial blood supply of hindlimb muscles of control rats and ligated rats. The results demonstrate that the sympathetic and pressor responses to lactic acid were significantly augmented after femoral occlusion compared with those in the control group. The data of this study suggest that enhanced ASIC3 expression in muscle afferent nerves contributes to the exaggerated reflex sympathetic and pressor responses to lactic acid as seen in arterial occlusion.

Moment-to-Moment Characteristics of the Relationship Between Arterial Pressure and Renal Interstitial Hydrostatic Pressure

The kidney is a key controller of the long-term level of arterial pressure, in part through pressure-natriuresis. Although direct coupling of changes in renal arterial pressure to renal interstitial hydrostatic pressure (RIHP) and consequent sodium excretion is well established, few studies have characterized the moment-to-moment aspects of this process. These studies characterized the short-term hemodynamic component of pressure-natriuresis in vivo before and after autonomic nervous system and renin-angiotensin system inhibition. Changes in RIHP were determined over a range of renal arterial pressures in Wistar rats receiving no treatment, a ganglionic blocker (hexamethonium; 20 mg/kg per hour IV), or an angiotensin II type 1 receptor blocker (losartan; 10 mg/kg per hour IV). After a series of changes in renal arterial pressure, a delay of only ≈1 second was found for the onset of RIHP responses that was independent of the stimulus magnitude and neurohumoral manipulation; however, completion of the full RIHP response was within ≈15 seconds for renal arterial pressure changes of ≤30 mm Hg. The overall slope of the renal arterial pressure- RIHP relationship (0.09±0.01) was also not affected by autonomic nervous system and renin-angiotensin system inhibition despite decreasing renal arterial pressure (↓40% and ↓28%, respectively). Separate assessment of this relationship above and below the prevailing arterial pressure revealed that the pressor versus the depressor portion was blunted (P<0.001), a difference that was abolished after autonomic nervous system and renin-angiotensin system inhibition. The results suggest that spontaneous changes in arterial pressure are coupled to moment-to-moment changes in RIHP over a wide range of pressures, emphasizing a likely role for the dynamic component of the renal arterial pressure-RIHP relationship in the modulation of sodium excretion and, hence, arterial pressure.

¿Es la edad un factor predictor en el desarrollo de hipertensión en pacientes con oclusión unilateral de la arteria renal secundario a trauma abdominal contuso que fueron tratados conservadoramente?

Objective To present 2 cases with unilateral renal artery occlusion after blunt trauma conservatively treated and review, in the literature, the role of age as a prognostic factor for the development of hypertension. Material and methods A 14 and 12 y/o male and female passengers, who were unrestrained in the back seat of a car, were involved in different motor vehicle accidents. Both remained in the seat and arrived at the Pediatric Emergency Department with normal vital signs. Computerized tomography scans showed unenhancing kidneys. Conservative management was advocated. Results After 38 and 36 months follow-up, respectively, normal renal function and arterial pressure. We found only 7 cases in the literature where age ≤16 was reported and treatment was conservative. Nine in total, hypertension developed in 2(22%). Conclusions No conclusion could be made with such a small sample. There is enough evidence in the literature supporting conservative management at all ages.

Multiple mechanisms act to maintain kidney oxygenation during renal ischemia in anesthetized rabbits

We examined the mechanisms that maintain stable renal tissue PO(2) during moderate renal ischemia, when changes in renal oxygen delivery (DO(2)) and consumption (VO(2)) are mismatched. When renal artery pressure (RAP) was reduced progressively from 80 to 40 mmHg, VO(2) (-38 ± 7%) was reduced more than DO(2) (-26 ± 4%). Electrical stimulation of the renal nerves (RNS) reduced DO(2) (-49 ± 4% at 2 Hz) more than VO(2) (-30 ± 7% at 2 Hz). Renal arterial infusion of angiotensin II reduced DO(2) (-38 ± 3%) but not VO(2) (+10 ± 10%). Despite mismatched changes in DO(2) and VO(2), renal tissue PO(2) remained remarkably stable at ≥40 mmHg RAP, during RNS at ≤2 Hz, and during angiotensin II infusion. The ratio of sodium reabsorption to VO(2) was reduced by all three ischemic stimuli. None of the stimuli significantly altered the gradients in PCO(2) or pH across the kidney. Fractional oxygen extraction increased and renal venous PO(2) fell during 2-Hz RNS and angiotensin II infusion, but not when RAP was reduced to 40 mmHg. Thus reduced renal VO(2) can help prevent tissue hypoxia during mild renal ischemia, but when renal VO(2) is reduced less than DO(2), other mechanisms prevent a fall in renal PO(2). These mechanisms do not include increased efficiency of renal oxygen utilization for sodium reabsorption or reduced washout of carbon dioxide from the kidney, leading to increased oxygen extraction. However, increased oxygen extraction could be driven by altered countercurrent exchange of carbon dioxide and/or oxygen between renal arteries and veins.

Exposure to a High-Fat Diet Alters Leptin Sensitivity and Elevates Renal Sympathetic Nerve Activity and Arterial Pressure in Rabbits

The activation of the sympathetic nervous system through the central actions of the adipokine leptin has been suggested as a major mechanism by which obesity contributes to the development of hypertension. However, direct evidence for elevated sympathetic activity in obesity has been limited to muscle. The present study examined the renal sympathetic nerve activity and cardiovascular effects of a high-fat diet (HFD), as well as the changes in the sensitivity to intracerebroventricular leptin. New Zealand white rabbits fed a 13.5% HFD for 4 weeks showed modest weight gain but a 2- to 3-fold greater accumulation of visceral fat compared with control rabbits. Mean arterial pressure, heart rate, and plasma norepinephrine concentration increased by 8%, 26%, and 87%, respectively (P<0.05), after 3 weeks of HFD. Renal sympathetic nerve activity was 48% higher (P<0.05) in HFD compared with control diet rabbits and was correlated to plasma leptin (r=0.87; P<0.01). Intracerebroventricular leptin administration (5 to 100 microg) increased mean arterial pressure similarly in both groups, but renal sympathetic nerve activity increased more in HFD-fed rabbits. By contrast, intracerebroventricular leptin produced less neurons expressing c-Fos in HFD compared with control rabbits in regions important for appetite and sympathetic actions of leptin (arcuate: -54%, paraventricular: -69%, and dorsomedial hypothalamus: -65%). These results suggest that visceral fat accumulation through consumption of a HFD leads to marked sympathetic activation, which is related to increased responsiveness to central sympathoexcitatory effects of leptin. The paradoxical reduction in hypothalamic neuronal activation by leptin suggests a marked "selective leptin resistance" in these animals.

Is age a predictor for the development of hypertension in conservatively managed unilateral renal artery occlusion secondary to blunt abdominal trauma?

ObjectiveTo present 2 cases with unilateral renal artery occlusion after blunt trauma conservatively treated and review, in the literature, the role of age as a prognostic factor for the development of hypertension. Material and methodsA 14 and 12 y/o male and female passengers, who were unrestrained in the back seat of a car, were involved in different motor vehicle accidents. Both remained in the seat and arrived at the Pediatric Emergency Department with normal vital signs. Computerized tomography scans showed unenhancing kidneys. Conservative management was advocated. ResultsAfter 38 and 36 months follow-up, respectively, normal renal function and arterial pressure. We found only 7 cases in the literature where age ≤16 was reported and treatment was conservative. Nine in total, hypertension developed in 2(22%). ConclusionsNo conclusion could be made with such a small sample. There is enough evidence in the literature supporting conservative management at all ages.

Long-term responses of renal sympathetic nerve activity and arterial pressure to chronic sino-aortic denervation in rats

Long-term responses of renal sympathetic nerve activity and arterial pressure to chronic sino-aortic denervation in rats

Sildenafil as a Protecting Drug for Warm Ischemic Kidney Transplants: Experimental Results

In an experimental model we studied the protective effects of the phosphodiesterase-5 inhibitor sildenafil on kidney grafts autotransplanted after 45 minutes of warm ischemia by vascular clamping, nephrectomy and 60 minutes of isolated hypothermic pump perfusion. A total of 14 laboratory minipigs were divided into group 1-7 administered 100 mg sildenafil orally 1.5 hours preoperatively and group 2-7 in which no sildenafil was given. Right single nephrectomy was completed after 45 minutes of warm ischemia by complete vascular clamping. Before autotransplantation all kidneys underwent 60 minutes of hypothermic pulsatile perfusion. Renal flow, arterial pressure and renal vascular resistance were recorded in real time for 60 minutes after autotransplantation. Nitric oxide levels were determined in blood samples from the renal vein at predefined intervals. Optical and electronic microscopy was done in all organs at the end of the procedure. In group 1 vs 2 renal vascular flow was significantly higher (155.30 vs 29.04 ml per minute per 100 gm) and renal vascular resistance was significantly lower (0.59 vs 3.10 mm Hg/ml per minute, each p <0.01). No significant differences were observed in systemic arterial pressure between groups 1 and 2 (84.08 and 84.65 mm Hg, respectively, p >0.05). Nitric oxide levels were significantly higher for all periods in group 1 (49.94 vs 16.85 muM, p <0.01). No significant differences were observed in histological studies, although endothelial cell structure was better preserved in the sildenafil group. To our knowledge our study suggests for the first time in the literature a positive effect of sildenafil in the immediate posttransplantation outcome of warm ischemic kidneys without secondary systemic effects.