Renal Blood Flow Velocity Research Articles

Endurance training reduces renal blood flow at rest in humans

Reductions in renal blood flow (RBF) after exercise training is less at a given absolute work rate. However, data regarding the effects of training on RBF at rest are minimal. The purpose of this study was to determine the effects of endurance training on RBF at rest. Forty-one subjects (25±1 yr, 17 M, 24 F) were randomly assigned to run (24) or cycle (17) 4 times/wk, 1 hr/day for 8 wk. After a 20 min rest period with the subject in the supine position, RBF velocity was measured using Doppler ultrasound for 5 min. Arterial blood pressure and heart rate were measured with a Dinamap. This protocol was repeated at rest both before and after training. Exercise training elicited a 19±2% increase in VO2peak. There were small but significant reductions in systolic (Δ3±1 mmHg), diastolic (Δ2±1 mmHg), and mean (Δ2±1 mmHg) arterial pressure (p<0.03) at rest after training. Heart rate was reduced from 66±2 to 59±2 beats/min (p<0.001). RBF velocity before training was 57.5±2.5 cm/s and was reduced to 49.7±2.2 cm/s (21±6%; p=0.002). Calculated renal vascular conductance decreased from 0.70±0.03 to 0.62±0.03 units (18±5%; p=0.01) after training. These results demonstrate that exercise training elicits marked reductions in RBF at rest in humans despite reported decreases in renal sympathetic nerve activity. This renal adaptation would decrease the over perfused kidneys and translocate more blood to other vascular beds. Supported by NIH HL077670 and DC006459.

Melatonin differentially affects vascular blood flow in humans

Melatonin is synthesized and released into the circulation by the pineal gland in a circadian rhythm. Melatonin has been demonstrated to differentially alter blood flow to assorted vascular beds by the activation of different melatonin receptors in animal models. The purpose of the present study was to determine the effect of melatonin on blood flow to various vascular beds in humans. Renal (Doppler ultrasound), forearm (venous occlusion plethysmography), and cerebral blood flow (transcranial Doppler), arterial blood pressure, and heart rate were measured in 10 healthy subjects (29±1 yr; 5 men and 5 women) in the supine position for 3 min. The protocol began 45 min after the ingestion of either melatonin (3 mg) or placebo (sucrose). Subjects returned at least 2 days later at the same time of day to repeat the trial after ingesting the other substance. Melatonin did not alter heart rate and mean arterial pressure. Renal blood flow velocity (RBFV) and renal vascular conductance (RVC) were lower during the melatonin trial compared with placebo (RBFV, 40.5±2.9 vs. 45.4±1.5 cm/s; and RVC, 0.47±0.02 vs. 0.54±0.01 cm·s(-1)·mmHg(-1), respectively). In contrast, forearm blood flow (FBF) and forearm vascular conductance (FVC) were greater with melatonin compared with placebo (FBF, 2.4±0.2 vs. 1.9±0.1 ml·100 ml(-1)·min(-1); and FVC, 0.029±0.003 vs. 0.023±0.002 arbitrary units, respectively). Melatonin did not alter cerebral blood flow measurements compared with placebo. Additionally, phentolamine (5-mg bolus) after melatonin reversed the decrease in RVC, suggesting that melatonin increases sympathetic outflow to the kidney to mediate renal vasoconstriction. In summary, exogenous melatonin differentially alters vascular blood flow in humans. These data suggest the complex nature of melatonin on the vasculature in humans.

Blood transfusions increase cerebral, splanchnic, and renal oxygenation in anemic preterm infants

Multiprobe near infrared spectroscopy (NIRS) has been used to study regional cerebral (rSO(2)C), splanchnic (rSO(2)S), and renal (rSO(2)R) tissue oxygenation in newborns. We used this method to study the effects of red blood cell (RBC) transfusions in anemic preterm infants to assess if thresholds for transfusions were appropriate for recognizing a clinical condition permitting tissue oxygenation improvement. Multiprobe NIRS (INVOS 5100, Somanetics) was applied during transfusion to 15 preterm infants with symptomatic anemia of prematurity (hematocrit level of <25%). rSO(2)C, rSO(2)S, and rSO(2)R were recorded at selected times, and then fractional oxygen cerebral extraction ratio [FOEC: (SaO(2)-rSO(2)C)/SaO(2)], fractional oxygen splanchnic extraction ratio [FOES: (SaO(2)-rSO(2)S)/SaO(2)], fractional oxygen renal extraction ratio [FOER: (SaO(2)-rSO(2)R)/SaO(2)], cerebrosplanchnic oxygenation ratio [CSOR: (rSO(2)S/rSO(2)C)], and cerebrorenal oxygenation ratio [CROR: (rSO(2)R/rSO(2)C)] were calculated. In addition, we used Doppler ultrasonography for evaluating cerebral blood flow (CBF), splanchnic blood flow (SBF), and renal blood flow (RBF) velocity. rSO(2)C, rSO(2)S, and rSO(2)R significantly increased during transfusions, while FOEC, FOES, and FOER decreased. CSOR and CROR increased during transfusions. CBF velocity decreased during the study period, while SBF and RBF velocities did not vary. RBC transfusions performed at used thresholds permitted an increase in cerebral, splanchnic, and renal oxygenation. The associated decreases in oxygen tissue extraction might suggest that transfusions were well timed for preventing tissue hypoxia or too early and theoretically prooxidant. Further studies could help to clarify this issue.

INTRARENAL BLOOD FLOW DOPPLER SPECTRA IN DIABETIC PATIENTS AND HYPERTENSIVE DIABETIC PATIENTS: PP.17.146

Objectives: The aim of the study was to determine the changes of Doppler spectra indices of intrarenal blood flow in diabetic patients with/without hypertension; to compare the changes of intrarenal vascular resistance in hypertensive diabetic patients with/without microalbuminuria. Methods: The 28 diabetic patients (Gr.D), 52 hypertensive patients (Gr.H), 208 diabetic hypertensive patients (Gr.HD) and 14 healthy people (control group). were included. The were no differences between the hypertensive groups in sex, age, BP-24 h levels and duration of arterial hypertension. Renal blood flow velocities profiles were detected by duplex scanning index in renal and arcuate intrarenal arteries; on the grounds of which resistive index in the segmental (RIs) and arcuate intrarenal arteries (RIar) was calculated. 24-hour ambulatory BP recordings were performed. Serum insulin concentration were measured by radioimmune method. 24-hour urinary protein excretion was determined by standart laboratory method. Results: 34,1% diabetic hypertensive patients, 13,3% hypertensive patients (P = 0,0005 vs Gr.HD) and 7,7% diabetic patients (P = 0,0245 vs Gr.HD) have microalbuminuria. Even normotensive diabetic patients show an increase in intrarenal vascular resistance: RIar levels were 0,63 ± 0,05 and 0,59 ± 0,04 in Gr.D vs 0,54 ± 0,06 and 0,48 ± 0,02 in the control group, respectively. Compared with pts of Gr.H, in pts of Gr.HD was observed more marked increase in intrarenal vascular resistance: RIar levels were 0,60 ± 0,05 in Gr.HD vs 0,57 ± 0,06 in Gr.H. In pts with microalbuminuria, the elevated indices of intrarenal vascular resistance were positively associated with duration of hypertension, age, levels of HbA1, triglycerides, total cholesterol and negatively associated with decrease in diastolic BP-day, diastolic BP-24 h and duration of diastolic arterial hypertension during daytime at disproportional increase in systolic BP. Conclusions: Our results show that the increase in intrarenal resistance is developed at earlier stages of diabetes. Hypertensive diabetic patients developed the increase in intrarenal resistance and/or microalbuminuria earlier as compared to hypertensive patients without diabetes.

Natural history and progression of atherosclerotic renal vascular stenosis

Date written: December 2008Final submission: October 2009

Endurance training reduces renal vasoconstriction to orthostatic stress

Endurance training has been associated with increased orthostatic intolerance. The purpose of the present study was to test the hypothesis that endurance training reduces renal vasoconstriction to orthostatic stress. Blood pressure, heart rate, and renal blood flow velocity were measured during a 25-min 60 degrees head-up tilt (HUT) test before and after 8 wk of endurance training in eight healthy sedentary subjects (26 +/- 1 yrs). Training elicited a 21 +/- 3% increase in peak oxygen uptake (V(O(2)peak)) and a reduction in heart rate at rest of 8 +/- 2 beats/min. During HUT, heart rate progressively increased (approximately 20 beats/min) over the 25-min HUT trial both before and after training. Systolic arterial blood pressure during HUT was unchanged with training, whereas diastolic arterial blood pressure was lower at the end of HUT after training. Before training renal blood flow velocity (Delta14 +/- 5 cm/s) and renal vascular conductance (Delta22 +/- 7%) decreased during HUT, whereas after training renal blood flow velocity (Delta2 +/- 5 cm/s) and renal vascular conductance (Delta1 +/- 12%) did not change significantly during HUT. Renal blood flow velocity and vascular conductance responses to HUT did not change in control subjects during the 8-wk period. These results demonstrate that endurance training reduces renal vasoconstriction during an orthostatic challenge and may contribute to training-induced orthostatic intolerance.

Effects of aerobic exercise training on sympathetic and renal responses to mental stress in humans

The effects of aerobic exercise training (ET) on muscle sympathetic nerve activity (MSNA) and renal vascular responses to mental stress (MS) have not been determined in humans. We hypothesized that aerobic ET would reduce MSNA and renal vasoconstriction during MS. MSNA, mean arterial pressure (MAP), heart rate, renal blood flow velocity (RBFV), and peak oxygen uptake (V(O2peak)) were recorded in 23 healthy adults. Fourteen subjects participated in 8 wk of aerobic ET, while nine subjects served as sedentary controls (Con). ET significantly increased V(O2peak) (Delta18 +/- 1%; P < 0.001) and decreased RBFV at rest (60 +/- 4 to 48 +/- 3 cm/s; P < 0.01), whereas Con did not alter V(O2peak) or RBFV. ET did not alter resting MSNA (11 +/- 1 to 9 +/- 1 bursts/min) or MAP (84 +/- 2 to 83 +/- 2 mmHg), and these findings were similar in the Con group. MS elicited similar increases in MSNA (approximately Delta2 bursts/min; P < 0.05), MAP (approximately Delta15 mmHg; P < 0.001), and heart rate (approximately Delta20 beats/min; P < 0.001) before and after ET, and the responses were not different between ET and Con. Likewise, MS elicited similar decreases in RBFV and renal vascular conductance before and after ET, and the responses were not different between ET and Con. Perceived stress levels during MS were similar before and after the 8-wk study in both ET and Con. In conclusion, ET does not alter MSNA and renal vascular responses to MS in healthy humans.

Real-time measurement of renal blood flow in healthy subjects using contrast-enhanced ultrasound.

Current methods for measuring renal blood flow (RBF) are time consuming and not widely available. Contrast-enhanced ultrasound (CEU) is a safe and noninvasive imaging technique suitable for assessment of tissue blood flow, which has been used clinically to assess myocardial blood flow. We tested the utility of CEU in monitoring changes in RBF in healthy volunteers. We utilized CEU to monitor the expected increase in RBF following a high protein meal in healthy adults. Renal cortical perfusion was assessed by CEU using low mechanical index (MI) power modulation Angio during continuous infusions of Definity. Following destruction of tissue microbubbles using ultrasound at a MI of 1.0, the rate of tissue replenishment with microbubbles and the plateau acoustic intensity (AI) were used to estimate the RBF velocity and cortical blood volume, respectively. Healthy adults (n = 19, mean age 26.6 yr) were enrolled. The A.beta parameter of CEU, representing mean RBF increased by 42.8%from a baseline of 17.05 +/- 6.23 to 23.60 +/- 6.76 dB/s 2 h after the ingestion of the high-protein meal (P = 0.002). Similarly, there was a 37.3%increase in the beta parameter, representing the geometric mean of blood velocity after the high protein meal (P < 0.001). The change in cortical blood volume was not significant (P = 0.89). Infusion time of Definity was 6.3 +/- 2.0 min. The ultrasound contrast agent was tolerated well with no serious adverse events. CEU is a fast, noninvasive, and practical imaging technique that may be useful for monitoring renal blood velocity, volume, and flow.

Assessment of a New Mathematical Model for the Computation of Numerical Parameters Related to Renal Cortical Blood Flow and Fractional Blood Volume by Contrast-Enhanced Ultrasound

We analyzed the value of a new mathematical model for the quantification of renal cortical blood flow and fractional blood volume by contrast-enhanced ultrasound after the injection of sulfur hexafluoride–filled microbubbles. A vessel-mimicking phantom experiment was preliminarily performed which showed that the effect of microbubble diffusion is negligible compared with the effect of liquid drag. Twelve healthy volunteers (7 male, 5 female; 27 to 48 years [ n = 6; group 1], and 61 to 80 years [ n = 6; group 2], respectively), with normal renal and cardiac function and not undergoing any pharmacologic treatment, were examined. In each volunteer, both kidneys were scanned after intravenous injection of sulfur hexafluoride–filled microbubbles at a slow rate (4.8 mL at a flow of 4.0 mL/min), and the refill kinetics of the renal cortex after microbubble destruction was evaluated by echo-signal intensity quantification. The progressive replenishment of the renal vessels was approximated both by standard negative exponential function and by the piecewise linear function resulting from our mathematical model. A better dataset approximation was provided by piecewise linear versus standard negative exponential function (overall mean square error: 0.44 vs. 0.51; p < 0.05, Wilcoxon test). The piecewise linear function provided a curve composed of four linear tracts ( n = 3 volunteers; 2 from group 1 and 1 from group 2), three linear tracts ( n = 6 volunteers; 3 from group 1 and 3 from group 2) or two linear tracts ( n = 3 volunteers; 1 from group 1 and 2 from group 2). The piecewise linear function versus standard negative exponential function improved data approximation for the computation of numerical values related to renal cortical blood flow velocity and fractional blood volume. (E-mail: quaia@univ.trieste.it)

Assessment of Renal Hemodynamic Effects of Nesiritide in Patients With Heart Failure Using Intravascular Doppler and Quantitative Angiography

We evaluated the magnitude and site of action of the nesiritide mediated renal vasodilatory effect in patients with heart failure (HF). Nesiritide, a recombinant human B-type natriuretic peptide is approved for the treatment of acute decompensated HF and has been shown to exert favorable hemodynamic, neurohormonal, and symptomatic effects. The renal effect of nesiritide in HF patients has not been well defined. In 15 patients with acute decompensated HF, intravascular Doppler and quantitative angiography of the renal artery were used to assess the effect of nesiritide on renal artery diameter and velocity time integral as well as renal blood flow and vascular resistance. Nesiritide was administered intravenously at a standard dose of 2 microg/kg bolus followed by a continuous infusion at a rate of 0.01 microg/kg/min. Assessment of nesiritide effect was made at 15 min. Nesiritide infusion was associated with a significant central hemodynamic effect including a fall in mean pulmonary artery pressure (36 +/- 12 mm Hg to 31 +/- 13 mm Hg, p < 0.001), mean pulmonary capillary wedge pressure (21 +/- 2 mm Hg to 15 +/- 10 mm Hg, p < 0.001), and systemic vascular resistance (1,995 +/- 532 dynes s cm(-5) to 1,563 +/- 504 dynes s cm(-5), r < 0.001), and an increase in cardiac output from 3.9 +/- 1.2 l/min to 4.6 +/- 1.6 l/min (p = 0.001). Nesiritide was also associated with a significant vasodilatory effect on the large conductance renal arteries resulting in an increase in renal artery diameter from 6.2 +/- 0.7 mm to 6.7 +/- 0.8 mm (p < 0.001). At the same time, there was a concomitant fall in mean renal artery pressure (99 +/- 17 mm Hg to 89 +/- 13 mm Hg, p = 0.002) and renal blood flow velocity time integral (27 +/- 15 cm/beat to 23 +/- 15 cm/beat, p = 0.008) and, therefore, no significant change in renal blood flow or renal vascular resistance. The nesiritide effect on the renal circulation in patients with HF is complex, with a marked vasodilatory action on the large, conductance renal arteries but a concomitant fall in velocity time integral and no effect on renal vascular resistance or renal blood flow. Lack of increase in renal blood flow may be due to a fall in renal blood pressure or an intrarenal vasoconstrictive effect.

Local prostaglandin blockade attenuates muscle mechanoreflex-mediated renal vasoconstriction during muscle stretch in humans

During exercise, muscle mechanoreflex-mediated sympathoexcitation evokes renal vasoconstriction. Animal studies suggest that prostaglandins generated within the contracting muscle sensitize muscle mechanoreflexes. Thus we hypothesized that local prostaglandin blockade would attenuate renal vasoconstriction during ischemic muscle stretch. Eleven healthy subjects performed static handgrip before and after local prostaglandin blockade (6 mg ketorolac tromethamine infused into the exercising forearm) via Bier block. Renal blood flow velocity (RBV; Duplex Ultrasound), mean arterial pressure (MAP; Finapres), and heart rate (HR; ECG) were obtained during handgrip, post-handgrip muscle ischemia (PHGMI) followed by PHGMI with passive forearm muscle stretch (PHGMI + stretch). Renal vascular resistance (RVR, calculated as MAP/RBV) was increased from baseline during all paradigms except during PHGMI + stretch after the ketorolac Bier block trial where RVR did not change from baseline. Before Bier block, RVR rose more during PHGMI + stretch than during PHGMI alone (P < .01). Similar results were found after a saline Bier block trial (Delta53 +/- 13% vs. Delta35 +/- 10%; P < 0.01). However, after ketorolac Bier block, RVR was not greater during PHGMI + stretch than during PHGMI alone [Delta39 +/- 8% vs. Delta40 +/- 12%; P = not significant (NS)]. HR and MAP responses were similar during PHGMI and PHGMI + stretch (P = NS). Passive muscle stretch during ischemia augments renal vasoconstriction, suggesting that ischemia sensitizes mechanically sensitive afferents. Inhibition of prostaglandin synthesis eliminates this mechanoreceptor sensitization-mediated constrictor responses. Thus mechanoreceptor sensitization in humans is linked to the production of prostaglandins.

Acute renal haemodynamic effects of radiocontrast media in patients undergoing left ventricular and coronary angiography

Tubular toxicity and renal ischaemia have been implicated in the pathogenesis of radiocontrast media induced nephropathy (CIN), but their respective role remains unclear. Aims. In order to evaluate changes in renal blood flow in response to intra-arterial contrast media administration, we aimed to continuously measure renal arterial perfusion by means of renal blood flow velocity (RBFV) during left ventricular and coronary angiography and subsequent coronary intervention in patients with chronic kidney disease (CKD). Ten patients (7 males, 63.4 +/- 11.7 years) with serum creatinine (SCr) >1.5 mg/dl participated in the study. The first five patients received low-osmolar iopromide and the others iso-osmolar iodixanol contrast medium. RBFV was measured using a 0.014-inch Doppler guide wire, which was inserted through a separate contralateral femoral sheath via a 5 F Cobra diagnostic catheter into the renal artery. Data were recorded at 500 Hz to allow beat-to-beat analysis of RBFV and pressure. All patients were pre-treated with acetylcysteine and hydration. Immediately after left ventricular angiography no significant changes in RBFV were detected. Over time, however, following repeated administration of the additional contrast medium into the coronary arteries, RBFV decreased significantly from baseline until the end of the investigation, 28.4 (19.1/42.7) to 22.9 (16.9/30.6) cm/s (median and quartiles; P = 0.005), in the absence of significant changes in systemic arterial blood pressure. In individual patients the reduction in RBVF varied from 3.7% to 39.5%. On average the decline in RBFV was more pronounced in patients receiving iopromide (from 41.6 cm/s to 29.3 cm/s) than in those receiving iodixanol (from 19.3 to 17.8 cm/s; P = 0.008 for the difference of relative decline). However, in the iopromide treated patients, coronary intervention was more frequently performed (5/5 versus 2/5) and the median duration of the procedure tended to be longer [85 (32-150) min versus 38 (27-110) min; P > 0.2]. The administration of non-ionic low-osmolal contrast media has no immediate effect on renal perfusion in patients with CKD. However, during the course of coronary angiography a gradual decline in renal blood flow may occur, the extent of which varies, presumably depending on individual pre-disposition as well as on the amount of the contrast medium.

Ultrasound Imaging of Renal Vaso-Occlusive Events in Transgenic Sickle Mice Exposed to Hypoxic Stress

One of the major clinical manifestations of sickle cell disease (SCD) is vaso-occlusive crisis in response to hypoxic exposure, leading to acute and chronic organ damages, especially in kidneys. In a SCD transgenic murine model, ultrasound imaging allowed us to characterize the circulatory changes in renal arteries during vaso-occlusive crisis. Cardiac output, heart rate and renal blood flow velocities (BFV) were measured in 10 male transgenic and 10 male wild-type (WT) mice with a conventional echograph (Vivid 7, GE Medical), before and after hypoxic exposure (8%O 2, 18h). To assess entrapment of red cells, histologic study of the kidneys was performed in both groups. Hypoxic exposure decreased heart rates in both groups (–17%, p < 0.001). Cardiac output remained stable in WT, and decreased in transgenic (–26%, p < 0.01). Peak systolic BFV in the renal artery was not modified in both groups. End-diastolic and mean BFV remained stable in WT, but decreased in sickle transgenic (–56%, p < 0.01 and –47%, p < 0.001, respectively). Transgenic mice displayed marked congestion in peritubular capillaries and glomerular abnormalities with trapped sickle red cells, whereas WT did not present any histologic injury. Five hours after hypoxic exposure, blood flow velocities returned to basal values in both groups. Decrease in end-diastolic and mean BFV in absence of peak systolic BFV after hypoxic exposure strongly indicated that the increase in vascular resistance in kidneys related to sickling of red cells. Thus, ultrasound imaging of the renal artery in mouse is a powerful, noninvasive, easy-to-repeat method to evidence circulatory changes in murine models of vascular renal human diseases. (E-mail: philippe.bonnin@lrb.aphp.fr)

Evaluation of the Abdominal Aorta and the Renal Arteries with an Intracardiac Echocardiography Probe Placed in the Inferior Vena Cava: A Feasibility Study

Ultrasound evaluation of the abdominal aorta and its branches is usually performed transabdominally. Not infrequently, the image quality is suboptimal. Recently, an intracardiac echocardiography probe has become commercially available. These probes are usually inserted intravenously and advanced to the right heart for diagnostic and monitoring purposes during procedures such as atrial septal defect closure and pulmonary vein isolation. Because of the close anatomic relation between the abdominal aorta and the inferior vena cava, we hypothesized that these probes would be useful in the evaluation of the abdominal aorta and the renal arteries. Sixteen patients with normal renal function and no history of hypertension who were undergoing a pulmonary vein isolation procedure or atrial septal defect closure were studied. In each patient, the intracardiac echocardiography probe was inserted in the femoral vein and advanced to the right atrium for the evaluation of the left atrium and the pulmonary veins during the procedure. At the end of the therapeutic procedure, the probe was withdrawn into the inferior vena cava for the evaluation of the aorta and renal arteries. High-resolution images of the abdominal aorta from the diaphragm to its bifurcation were easily obtained in all patients. These images allowed for the evaluation of arterial size, shape, and blood flow. Both renal arteries were easily visualized in each patient. With the probe in the inferior vena cava, both renal arteries were parallel to the imaging plane and, therefore, accurate measurement of renal blood flow velocity and individual renal blood flow were measured.

Renal vasoconstrictor responses to static exercise during orthostatic stress in humans: effects of the muscle mechano‐ and the baroreflexes

Renal circulatory adjustments to stress contribute to blood pressure and volume regulation. Both handgrip (HG) and disengagement of baroreflexes with lower body negative pressure (LBNP) can engage the sympathetic nervous system (SNS). However, the effect of simultaneous HG and LBNP on the renal circulation in humans is not known. Eighteen young healthy volunteers were studied. Beat-to-beat changes in renal blood flow velocity (RBV; Duplex Ultrasound), mean arterial pressure (MAP; Finapres) and heart rate (ECG) were monitored during (a) 15 s HG at 30% maximum voluntary contraction (MVC); (b) LBNP at -10 and -30 mmHg (each level for 5 min); and (c) 15 s HG (at 30% MVC) during LBNP at both levels. Renal vascular resistance index (RVR units) was calculated by dividing MAP by RBV. The increases in RVR during HG alone (12 +/- 6%) were not different from the responses noted during combined HG and LBNP (17 +/- 6% at -10 mmHg and 25 +/- 8% at -30 mmHg). These results suggest occlusion occurs between a neural circuit engaged during 15 s of HG (central command and/or the muscle mechanoreflex) and a circuit activated by LBNP. In additional experiments (n = 6), similar non-algebraic summation of RVR was seen during 15 s involuntary biceps contractions (engages only muscle reflexes) and LBNP. With respect to RVR, neural occlusion occurs between baroreflexes and the muscle mechanoreflex. Muscle mechanoreflex mediated renal vasoconstriction during short bouts of HG is not influenced by baroreflex disengagement.

Renal Circulatory Effects of Acetazolamide in Patients With Essential Hypertension

Reports indicate that acetazolamide (ACZ) induces the vasodilation of all vessels in animal models, as well as in small and medium kidney vessels in animal models. However, the effect of ACZ on the renal circulation of patients with essential hypertension remains unknown. In this study we examined the effects of a carbonic anhydrase inhibitor, acetazolamide (ACZ), on the renal circulation of patients with essential hypertension. We directly infused 1000 mg of ACZ into the main renal arteries of 10 patients with essential hypertension who had undergone cardiac catheterization. We then evaluated the effects of ACZ upon heart rate, renal artery blood pressure (BP), renal artery cross-sectional area, renal Doppler blood flow velocity, renal blood flow (RBF), and renal vascular resistance (RVR). The infusion of ACZ was not associated with any significant changes in heart rate or in systolic or diastolic BP. However, the velocity-time integral was increased by 11.1% +/- 7.2%, from 17.6 +/- 1.8 to 20.0 +/- 3.7 cm (P = .009); RBF was increased by 39% +/- 21%, from 300 +/- 43 to 422 +/- 96 mL/min/m(2) (P = .002); and RVR was reduced by 38% +/- 20% from 24,351 +/- 2,291 to 17,651 +/- 2,731 dynes.sec.cm(-5) (P < .01). In contrast the cross-sectional area of the renal artery did not change. The results of the present study demonstrated that ACZ has a potent vasodilatory effect on the renal circulation of patients with essential hypertension, leading to an obvious decrease in RVR and an increase in RBF.

Influence of sex and active muscle mass on renal vascular responses during static exercise

During exercise, reflex renal vasoconstriction helps maintain blood pressure and redistributes blood flow to the contracting muscle. Sex and muscle mass have been shown to influence certain cardiovascular responses to exercise. Whether sex and/or muscle mass influence renal vasoconstrictor responses to exercise is unknown. We studied healthy men (n = 10) and women (n = 10) matched for age and body mass index during handgrip (HG, small muscle mass) and quadriceps contraction (QC, large muscle mass) as beat-to-beat changes in renal blood flow velocity (RBV; duplex ultrasound), mean arterial pressure (MAP; Finapres), and heart rate (ECG) were monitored. Renal vascular resistance (RVR) index was calculated as MAP / RBV. Responses to HG vs. QC were compared in 13 subjects. We found that 1) RVR responses to short (15-s) bouts and fatiguing HG were similar in men and women (change in RVR during 15-s HG at 70% of maximum voluntary contraction = 23 +/- 4 and 31 +/- 4% in men and women, respectively, P = not significant); 2) post-HG circulatory responses were similar in men and women; and 3) HG and QC were similar during short (15-s) bouts (change in RVR during HG at 50% of maximum voluntary contraction = 19 +/- 3 and 18 +/- 5% for arm and leg, respectively, P = not significant). Our findings suggest that muscle reflex-mediated renal vasoconstriction is similar in men and women during static exercise. Moreover, muscle mass does not contribute to the magnitude of the reflex renal vasoconstrictor response seen with muscle contraction.

Effects of Calcium Channel Blockade on Angiotensin II-Induced Peritubular Ischemia in Rats

Recent studies have indicated that derangement of peritubular capillary (PTC) circulation with consequent tubulointerstitial hypoxia plays a pivotal role in the pathogenesis of renal injury. The present study was performed to determine whether azelnidipine, a new dihydropyridine calcium channel blocker, attenuates angiotensin II (AngII)-induced peritubular ischemia in anesthetized rats. The superficial PTCs were visualized directly using an intravital fluorescence videomicroscope system, and the PTC blood flow was evaluated by analyzing the velocity of fluorescein isothiocyanate-labeled erythrocytes. Intravenous infusion of AngII (50 ng/kg/min, 10 min) significantly increased mean arterial pressure (MAP) and renal vascular resistance (RVR) (by 35 +/- 3% and 110 +/- 32%, respectively), and decreased total renal blood flow (RBF) and PTC erythrocyte velocity (by -34 +/- 4 and -37 +/- 1%, respectively). Treatment with azelnidipine (5 microg/kg/min i.v., 10 min) had no effect on basal MAP, RBF, RVR, or PTC erythrocyte velocity. However, azelnidipine markedly attenuated the AngII-induced increases in MAP (7 +/- 3%) and RVR (40 +/- 4%) and decreases in RBF (-24 +/- 1%) and PTC erythrocyte velocity (-22 +/- 1%). Similar attenuation in the AngII-induced responses of MAP, RBF, RVR, and PTC erythrocyte velocity were observed in rats treated with a higher dose of azelnidipine (20 microg/kg/min i.v., 10 min), which significantly decreased basal MAP and RVR and increased RBF and PTC erythrocyte velocity. These data suggest that calcium channel blockade attenuates AngII-induced peritubular ischemia, which may be involved in its beneficial effects on renal injury.

Local intra-renal fenoldopam infusion causes greater increases in renal artery flow velocity than systemic intravenous fenoldopam infusion: a pilot study.

Typical intravenous fenoldopam doses result in only minimal increases in renal blood flow and glomerular filtration, while higher doses are associated with systemic hypotension. We hypothesized that local infusion of fenoldopam into the renal arteries would enhance renal perfusion with reduction of arterial hypotension. Of 20 patients with renal impairment undergoing coronary intervention, 10 received infusion of fenoldopam into the left renal artery (IR). Doses were increased progressively (0.1,0.2,0.4 mcg/kg/min) at 5 min intervals, separated by a 10 min "wash out" period without drug application. Average and maximum peak renal blood flow velocities (APV and MPV) were measured using a flow-wire. A comparison group of 10 patients received renal flow measurements during IV fenoldopam application using the same escalating dose protocol without a drug-free period.The average peak flow velocity increased from 29.9+/-10.7 cm/s in the IR group and 25.9+/-7.7 cm/s in the IV group at baseline (p=ns) to 50.0+/-13.1 cm/s (IR) versus 31.0+/-11.9 cm/s (IV) at the maximum dose level (p=0.011). There was a trend towards attenuated reduction of the systemic pressure in the IR group compared to the IV group. In patients with renal insufficiency, local renal infusion of fenoldopam resulted in an approximately 50% increase in renal artery velocities without substantial blood pressure reduction compared to IV fenoldopam.

Renal vascular response to static handgrip exercise: sympathetic vs. autoregulatory control

Static exercise causes activation of the sympathetic nervous system, which results in increased blood pressure (BP) and renal vascular resistance (RVR). The question arises as to whether renal vasoconstriction that occurs during static exercise is due to sympathetic activation and/or related to a pressure-dependent renal autoregulatory mechanism. To address this issue, we monitored renal blood flow velocity (RBV) responses to two different handgrip (HG) exercise paradigms in 7 kidney transplant recipients (RTX) and 11 age-matched healthy control subjects. Transplanted kidneys are functionally denervated. Beat-by-beat analyses of changes in RBV (observed via duplex ultrasound), BP, and heart rate were performed during HG exercise in all subjects. An index of RVR was calculated as BP/RBV. In protocol 1, fatiguing HG exercise (40% of maximum voluntary contraction) led to significant increases in RVR in both groups. However, at the end of exercise, RVR was more than fourfold higher in control subjects than in the RTX group (88 vs. 20% increase over baseline; interaction, P < 0.001). In protocol 2, short bouts of HG exercise (15 s) led to significant increases in RVR at higher workloads (50 and 70% of maximum voluntary contraction) in the control subjects (P < 0.001). RVR did not increase in the RTX group. In conclusion, we observed grossly attenuated renal vasoconstrictor responses to exercise in RTX subjects, in whom transplanted kidneys were considered functionally denervated. Our results suggest that renal vasoconstrictor responses to exercise in conscious humans are mainly dependent on activation of a neural mechanism.