Renal Blood Flow In Dogs Research Articles

Evaluation of Renal Blood Flow in Dogs during Short-Term Human-Dose Epoprostenol Administration Using Pulsed Doppler and Contrast-Enhanced Ultrasonography.

Simple SummarySince there is a lack of information regarding how epoprostenol, a prostacyclin, affects canine renal blood flow (RBF), we investigated the effects of short-term administration of epoprostenol at human doses of 2, 5, and 10 ng/kg/min intravenously for 20 min on RBF in six healthy dogs under anesthesia. The effects of short-term administration were investigated. As the dose of epoprostenol increased, peak systolic and end diastolic velocities of the renal arteries, maximum and minimum venous flow velocities of the interlobular and renal veins, and heart rate all tended to increase. However, these increases were not significant. These results indicate that the administration of human doses of epoprostenol to dogs does not produce significant changes in renal or systemic circulation.Prostacyclin is an in vivo bioactive substance that regulates renal blood flow (RBF). Information regarding how epoprostenol, a prostacyclin preparation, affects RBF in dogs is lacking. We investigated the effects of short-term epoprostenol administration on RBF in six healthy dogs under anesthesia by administering it intravenously at human doses—2, 5, and 10 ng/kg/min for 20 min. RBF was evaluated before and during epoprostenol administration using pulsed Doppler ultrasonography, and renal perfusion was evaluated using contrast-enhanced ultrasonography. Effects on renal and systemic circulation were evaluated by measuring systolic arterial, mean arterial, diastolic arterial, pulmonary arterial, mean right atrial, and pulmonary capillary wedge pressures; heart rate; and cardiac output. Kruskal–Wallis and Bonferroni multiple comparison tests and Spearman’s rank correlation coefficient were used for statistical analyses. As epoprostenol dosage increased, the peak systolic and end diastolic velocity of the renal artery, maximum and minimum venous flow velocities of the interlobular and renal veins, and heart rate all tended to increase, although not significantly. Our results indicate that human-dose epoprostenol administration in dogs does not cause significant changes in renal or systemic circulation. However, the human doses used may have been too low to produce a clinical effect in dogs.

Use of quantitative contrast-enhanced ultrasonography to detect diffuse renal changes in Beagles with iatrogenic hypercortisolism

To determine the feasibility of quantitative contrast-enhanced ultrasonography (CEUS) for detection of changes in renal blood flow in dogs before and after hydrocortisone administration. 11 Beagles. Dogs were randomly assigned to 2 treatment groups: oral administration of hydrocortisone (9.6 mg/kg; n = 6) or a placebo (5; control group) twice a day for 4 months, after which the dose was tapered until treatment cessation at 6 months. Before treatment began and at 1, 4, and 6 months after, CEUS of the left kidney was performed by IV injection of ultrasonography microbubbles. Images were digitized, and time-intensity curves were generated from regions of interest in the renal cortex and medulla. Changes in blood flow were determined as measured via contrast agent (baseline [background] intensity, peak intensity, area under the curve, arrival time of contrast agent, time-to-peak intensity, and speed of contrast agent transport). Significant increases in peak intensity, compared with that in control dogs, were observed in the renal cortex and medulla of hydrocortisone-treated dogs 1 and 4 months after treatment began. Baseline intensity changed similarly. A significant increase from control values was also apparent in area under the curve for the renal cortex 4 months after hydrocortisone treatment began and in the renal medulla 1 and 4 months after treatment began. A significant time effect with typical time course was observed, corresponding with the period during which hydrocortisone was administered. No difference was evident in the other variables between treated and control dogs. Quantitative CEUS allowed detection of differences in certain markers of renal blood flow between dogs treated orally with and without hydrocortisone. Additional studies are needed to investigate the usefulness of quantitative CEUS in the diagnosis of diffuse renal lesions.

Chronic Glucose Infusion Increases Tubular Sodium Reabsorption and Renal Blood Flow in Dogs

It is not known whether hyperinsulinemia and/or hyperglycemia in metabolic syndrome contribute to the associated hypertension through chronic antinatriuretic actions. We tested this using chronic iv. glucose infusion to increase plasma insulin and glucose concentrations comparable to those measured in metabolic syndrome, and used 24 hr/day methods for measuring mean arterial pressure (MAP; DSI) and renal blood flow (RBF; Transonic). Blood glucose increased ~ 10 mg/dl over the 6‐day glucose infusion period, and plasma insulin increased from 28±4 to 45±12 µU/ml. Urinary sodium excretion averaged 70±8 mEq/d during control, decreased to 49±5 mEq/d on day 1 of glucose, and averaged 51±6 mEq/d over the 6 days. RBF averaged 123±17 ml/min during control, increased to 137±19 on day 1, and averaged 153±17 by day 6 of glucose. Plasma renin activity increased 3‐fold, and all variables returned to control values during recovery. MAP did not increase significantly. However, there was no tendency for MAP to decrease, eliminating pressure natriuresis as a mechanism for the sodium retention. This confirms our earlier report that glucose infusion causes sustained antinatriuresis in dogs, and the renal vasodilation indicates that tubular reabsorption is the mechanism. The renin and RBF responses are consistent with a role for the macula densa, but that and the reason why MAP did not increase require further study. HL56259, HL75625

Chronic glucose infusion causes sustained increases in tubular sodium reabsorption and renal blood flow in dogs

This study tested the hypothesis that inducing hyperinsulinemia and hyperglycemia in dogs, by infusing glucose chronically intravenously, would increase tubular sodium reabsorption and cause hypertension. Glucose was infused for 6 days (14 mg.kg(-1).min(-1) iv) in five uninephrectomized (UNX) dogs. Mean arterial pressure (MAP) and renal blood flow (RBF) were measured 18 h/day using DSI pressure units and Transonic flow probes, respectively. Urinary sodium excretion (UNaV) decreased significantly on day 1 and remained decreased over the 6 days, coupled with a significant, sustained increase in RBF, averaging approximately 20% above control on day 6. Glomerular filtration rate and plasma renin activity (PRA) also increased. However, although MAP tended to increase, this was not statistically significant. Therefore, the glucose infusion was repeated in six dogs with 70% surgical reduction in kidney mass (RKM) and high salt intake. Blood glucose and plasma insulin increased similar to the UNX dogs, and there was significant sodium retention, but MAP still did not increase. Interestingly, the increases in PRA and RBF were prevented in the RKM dogs. The decrease in UNaV, increased RBF, and slightly elevated MAP show that glucose infusion in dogs caused a sustained increase in tubular sodium reabsorption by a mechanism independent of pressure natriuresis. The accompanying increase in PRA, together with the failure of either RBF or PRA to increase in the RKM dogs, suggests the site of tubular reabsorption was before the macula densa. However, the volume retention and peripheral edema suggest that systemic vasodilation offsets any potential renal actions to increase MAP in this experimental model in dogs.

Chronic renal blood flow measurement in dogs by transit-time ultrasound flowmetry

To test the validity of transit-time ultrasound flowmetry for chronic measurement of renal blood flow in dogs, we compared this method with the renal clearance of para-aminohippuric acid (C PAH) (corrected for hematocrit), and with direct volumetric measurements. When flow-probes were implanted without silastic sheeting to stabilize the implant, there was significant disparity between the (within-dog) mean levels of renal blood flow estimated by flow-probe and C PAH. In contrast, when the flow-probe implants were stabilized with silicone sheeting, there was close agreement in each dog between the flow rates measured by the two methods. When flow-probes were calibrated volumetrically in situ, there was a close linear relationship between flow derived from the flow-probe and that measured volumetrically ( r = 0.98 ± 0.02). We conclude that valid, chronic measurement of renal blood flow in dogs can be achieved using transit-time ultrasound flowmetry, provided the implant is stabilized with silicone sheeting.

The effects of pulsatile cardiopulmonary bypass on cerebral and renal blood flow in dogs

Objective: The purpose of this study was to determine the effects of pulsatility on cerebral blood flow, cerebral metabolism, and renal blood flow over a range of cardiopulmonary bypass temperature and flow conditions. Design/Setting: The investigation was prospective, randomized, and performed in a canine physiology laboratory at the Mayo Foundation. Participants and Interventions: Anesthetized dogs were studied during pulsatile ( n = 9) or nonpulsatile ( n = 10) cardiopulmonary bypass at two flow rates (2.4 and 1.2 L/min/m 2) at each of three temperatures (37°, 32°, and 27°C). Pulsatility was achieved by use of a pediatric intraaortic balloon pump. Cerebral blood flow and metabolic rate were determined using the sagittal sinus outflow method. Renal blood flow was determined by a periarterial ultrasonic flow probe. Measurements and Main Results: In the pulsatile group, a pulse pressure of 29 mmHg had no effect on cerebral blood flow or metabolism at any temperature under either flow condition. Renal blood flow was also unaffected by pulsatility, but decreased with hypothermia and reduced pump flow. Pulsatility also did not attenuate the systemic effects of normothermic hypoperfusion. Conclusions: Pulsatility has no significant effect on cerebral or renal perfusion over a broad range of cardiopulmonary bypass temperature and flow conditions. Cerebral blood flow and metabolism were functions of temperature but not pulsatility or flow rate. Renal blood flow was affected by both temperature and cardiopulmonary bypass flow rate but not by pulsatility. Finally, central nervous system perfusion may be preserved under low-flow cardiopulmonary bypass conditions by shunting of perfusion from splanchnic vascular beds.

Activation of the Endothelium-Derived Relaxing Factor System in Acute Unilateral Ureteral Obstruction

Purpose To investigate the effects of L-arginine, a substrate for nitric oxide (NO) synthase, on renal hemodynamics in acute ureteral obstruction (UUO). Materials and Methods Renal blood flow (RBF) and ureteral pressure (UP) were measured in anesthetized dogs with or without UUO. Results In 9 dogs (Group 1), RBF was 212 +/− 13 ml./min. before UUO, and significantly increased to 302 +/− 18 and 268 +/− 9 ml./min. at 90 and 140 min. post-UUO, respectively, associated with a marked increase in UP from 3 +/− 1 mm. Hg to 73 +/− 5 and 83 +/− 2 mm. Hg at 90 and 140 min. post-UUO, respectively. In 6 dogs (Group 2) prostaglandin synthesis was inhibited with meclofenamate (5 mg./kg., i.v.). After UUO, RBF did not change significantly and the increase in UP was markedly attenuated when compared with Group 1, as UP rose only to 27 +/− 3 and 34 +/− 4 mm. Hg at 90 and 140 min. post-UUO, respectively. In 6 dogs pre-treated with meclofenamate, L-arginine was infused into the renal artery at 5 mg./kg./min. at 90 min. after UUO (Group 3). Prostaglandin synthesis inhibition prevented renal vasodilation after UUO and significantly attenuated the increase in UP. Upon infusion of L-arginine, RBF and UP rose sharply from 202 +/− 16 ml./min. and 24 +/− 6 mm. Hg to 264 +/− 22 ml./min. and 70 +/− 4 mm. Hg, respectively, at 140 min. post-UUO (p <0.001), values approaching those in Group 1. In sham-operated dogs, L-arginine infusion did not alter RBF in dogs with or without pretreatment with meclofenamate. Conclusion In UUO the L-arginine-NO pathway is activated, contributing to renal vasodilation and a marked increase in UP.

Vasodilation induced by vasopressin V2 receptor stimulation in afferent arterioles

We have previously reported that vasopressin (AVP) V2 receptor stimulation increased renal blood flow in dogs anesthetized with pentobarbital. In this study, we examined the direct effects of AVP on afferent arterioles to clarify the role played by V2 receptors in regulating afferent arteriolar tone. We microdissected a superficial afferent arteriole with glomerulus from the kidney of a New Zealand White rabbit. Each afferent arteriole was cannulated with a pipette system and microperfused in vitro at 60 mm Hg. The effects of vasoactive substances were evaluated by changes in the lumen diameter of afferent arterioles. We found that AVP decreased the lumen diameter of microperfused afferent arterioles dose-dependently and that a V1 antagonist, OPC21268, inhibited the vasoconstrictor action of AVP. However, AVP 10(-8) M increased the lumen diameter of norepinephrine (NE)-constricted afferent arterioles pretreated with OPC21268 (OPC + NE, 8.2 +/- 0.7 microns; OPC + NE + AVP, 9.9 +/- 0.9 microns*; *P < 0.05, N = 13). This vasodilatory effect of AVP was abolished by pretreatment with a V2 antagonist, OPC31260. Desmopressin (dDAVP), a V2 agonist, increased the lumen diameter of the NE-constricted afferent arterioles (NE, 7.4 +/- 0.9 microns; NE + dDAVP, 10.1 +/- 0.7 microns*; *P < 0.05, N = 9). These results suggest that AVP V2 receptors are present in rabbit afferent arterioles and that V2 receptor stimulation induces vasodilation in rabbit afferent arterioles.

Positron emission tomography in the study of acute radiation effects on renal blood flow in dogs.

Renal blood flow measurements have been carried out by means of positron emission tomography (PET) to facilitate the detection of radiation-induced injuries. The advantages of the method employed in animal experiments are described.

Effect of l-NG-Nitro-Arginine, Inhibitor of Nitric Oxide Synthesis, on Autoregulation of Renal Blood Flow in Dogs

The present experiments were designed to evaluate the importance of nitric oxide in the regulation of renal hemodynamics and the autoregulation of renal blood flow (RBF) in anesthetized dogs. RBF was measured by an electromagnetic flowmeter, and renal arterial pressure (RAP) was varied by an adjustable aortic clamp. The RAP-RBF relations were examined during the intrarenal infusion of saline or agents. The intrarenal infusion of l-NG-nitro-arginine (l-NNA, 40μg/kg-min) at normal Rap decreased RBF and urine flow (UF), while the infusion of larginine-HCI(1 mg/kg.min) increased RBF and UF. Both agents did not affect the glomerular filteration rate and mean arterial pressure. The autoregulation of RBF was impaired during the l-NNA infusion. The L-arginine infusion did not affect autoregulatory efficiency. When l-NNA (40 μg/kg-min) and l-arginine were infused simulataneously into the renal artery, the autoregulation of RBF was maintained. However, a higher dose of l-NNA (200 μg/kg-min) impaired the autoregulation of RBF. These results suggest that the basal production and/or the release of nitric oxide contributes to the regulation of renal hemodynamics and urine formation. During the reduction of RAP, nitric oxide may play an important role in the autoregulation of RBF.

Effect of L-NG-nitro-arginine, inhibitor of nitric oxide synthesis, on autoregulation of renal blood flow in dogs.

The present experiments were designed to evaluate the importance of nitric oxide in the regulation of renal hemodynamics and the autoregulation of renal blood flow (RBF) in anesthetized dogs. RBF was measured by an electromagnetic flowmeter, and renal arterial pressure (RAP) was varied by an adjustable aortic clamp. The RAP-RBF relations were examined during the intrarenal infusion of saline or agents. The intrarenal infusion of L-NG-nitro-arginine (L-NNA, 40 micrograms/kg.min) at normal RAP decreased RBF and urine flow (UF), while the infusion of L-arginine.HCI (1 mg/kg.min) increased RBF and UF. Both agents did not affect the glomerular filtration rate and mean arterial pressure. The autoregulation of RBF was impaired during the L-NNA infusion. The L-arginine infusion did not affect autoregulatory efficiency. When L-NNA (40 micrograms/kg.min) and L-arginine were infused simultaneously into the renal artery, the autoregulation of RBF was maintained. However, a higher dose of L-NNA (200 micrograms/kg.min) impaired the autoregulation of RBF. These results suggest that the basal production and/or the release of nitric oxide contributes to the regulation of renal hemodynamics and urine formation. During the reduction of RAP, nitric oxide may play an important role in the autoregulation of RBF.

1/f fluctuations in arterial pressure and regulation of renal blood flow in dogs

To determine whether renal blood flow is regulated against spontaneous fluctuations in arterial pressure and to estimate the frequency band of the regulation, we measured arterial pressure and renal blood flow continuously over several days in conscious dogs. Mean arterial blood pressure showed broad band fluctuations and behaved as a 1/f process, indicating that the blood pressure record is a fractal curve and therefore scale invariant. The fluctuations in arterial pressure caused attenuated fluctuations in renal blood flow; the gain was about -6.5 +/- 0.5 dB through all sampled frequencies greater than or equal to 4 cycle/day. The kidney did not attenuate the blood pressure signal at the lowest frequencies. The results show that renal blood flow is better regulated against fluctuations in pressure at frequencies greater than or equal to 4 cycle/day than it is at lower frequencies. Although there are no direct tests of the underlying regulatory mechanisms, we argue that the responses are generated locally and can be identified with renal autoregulation.

Inhibitory Effects of Trifluoperazine and Chlorpromazine, Calmodulin Inhibitor, on Autoregulation of Renal Blood Flow

An intra-arterial infusion of a calmodulin inhibitor trifluoperazine (3 mg/min) or chlorpromazine (5 mg/min) caused obvious inhibition of autoregulation of renal blood flow in dogs. Simultaneous infusion of CaCl2 (30 mg/min) or Ca channel activator BAY K 8644 (5 μg/min) with these calmodulin inhibitors reduced renal blood flow, but could not block the inhibitory activity of calmodulin inhibitors on the autoregulation. The present experiment shows the contribution of the Ca-calmodulin system to the mechanism of autoregulation of renal blood flow.

Inhibitory effects of trifluoperazine and chlorpromazine, calmodulin inhibitor, on autoregulation of renal blood flow.

An intra-arterial infusion of a calmodulin inhibitor trifluoperazine (3 mg/min) or chlorpromazine (5 mg/min) caused obvious inhibition of autoregulation of renal blood flow in dogs. Simultaneous infusion of CaCl2 (30 mg/min) or Ca channel activator BAY K 8644 (5 micrograms/min) with these calmodulin inhibitors reduced renal blood flow, but could not block the inhibitory activity of calmodulin inhibitors on the autoregulation. The present experiment shows the contribution of the Ca-calmodulin system to the mechanism of autoregulation of renal blood flow.

Effect of Thromboxane Inhibition on Renal Blood Flow in Dogs with Complete Unilateral Ureteral Obstruction

The effect of the thromboxane synthetase inhibitior OKY-046 on renal blood flow and ureteral pressure in awake dogs during 18 hours of complete unilateral ureteral obstruction was studied. OKY-046 was infused continuously throughout the period of obstruction and post-release. Renal blood flow and ureteral pressure were constantly monitored during the study. Urinary thromboxane B2 and prostaglandin E2 excretion served as markers for inhibition of renal thromboxane A2 synthesis. The triphasic relationship between ipsilateral renal blood flow and ureteral pressure previously found following unilateral ureteral obstruction was observed despite OKY-046 infusion. Inhibition of ipsilateral urinary thromboxane B2 excretion was greater than 90% compared to control while ipsilateral urinary prostaglandin E2 excretion was not consistently decreased showing specific thromboxane inhibition. These results suggest that urinary thromboxane B2 may serve as a useful marker for determining the effects of inhibition on renal thromboxane A2 production. At the level of inhibition of thromboxane synthesis achieved we did not observe any change in the late decrease in renal blood flow which is typically seen with chronic unilateral ureteral obstruction.

Effects of ouabain on autoregulation of renal blood flow in dogs

Effects of ouabain on the autoregulation of renal blood flow (RBF) and renin release were examined in filtering and nonfiltering kidneys of anesthetized dogs. Autoregulation of RBF was observed in both kidneys; however, autoregulation in the nonfiltering kidney was comparatively less efficient. These findings indicate that both the myogenic mechanism via a sensor element in the afferent arteriole, a so-called baroreceptor, and the tubuloglomerular feedback mechanism via the macula densa are essential for complete autoregulation. In both the control and nonfiltering kidney, intrarenal arterial infusion of ouabain abolished the autoregulation of RBF and glomerular filtration rate, with no change in the renal vascular sensitivity to vasoactive substances or in renin release induced by pressure reduction. Since various vasoactive drugs elicited a normal vascular response, it appears that the site of action of ouabain was not the vascular contractile elements; at least, an impairment of autoregulation during ouabain infusion was apparently not due to a defect in these elements. These results suggest the possible existence of another mediator, a sensor element in the afferent arteriole that is affected by ouabain. Ouabain may abolish the autoregulation of RBF and renin release via a modification of this baroreceptor in the afferent arteriole as well as through inhibition of the macula densa.

Assessment of renal blood flow in dogs: analysis of I-hippuran blood clearance in healthy dogs and in dogs with proteinuria

In 30 clinically healthy dogs (weights 7.5 to 57 kg) and in 41 proteinuric dogs the 131I-hippuran blood disappearance curve after single injection was determined (0 to 90 minutes), described by a bi-exponential function and analysed according to a two compartment model. The dependence of the blood clearance (C), representing an effective renal blood flow, on the bodyweight (W) (kg) could be described with both a linear function (C = 61 + 13.2 W ml min-1) and a power function (C = 30.56 W0.79 ml min-1) in the healthy dogs. The results of the regression between blood clearance and bodyweight were reproducible (r = 0.92, n = 10 residual error 12 per cent, P less than 0.01).

Effect of region assignment on relative renal blood flow estimates using radionuclides.

To determine the value of the initial phase of the Tc-99m DTPA renogram in the direct estimation of relative renal blood flow in dogs, the ratios of the slopes of renal time-activity curves were compared with the ratios of measured blood flow. Radionuclide results were dependent on region-of-interest (ROI) and background ROI assignment, and correlated well with measured relative flow only with a maximum renal outline region. Curve slope ratios correlated well with measured flow ratios with and without background correction, while 1- to 2-minute uptake ratios correlated well only when corrected for background.

Effect of adenosine on the distribution of renal blood flow in dogs.

Effect of adenosine on the distribution of renal blood flow in dogs.

Effect of dehydration on renal blood flow in dog.

The effect of dehydration on intrarenal blood flow was investigated in 11 dogs, using polarographic determination of H2-gas desaturation for measuring local blood flow in inner cortex (ICF) and outer cortex (OCF). Dehydration was induced by 48 h water deprivation +2-300 mg ethacrynic acid (EA) per os the day before the experiment. Compared to a control group (n=9) ICF was markedly reduced to 2.40 +/- 0.47 ml/min X g (control 3.23 +/- 0.64) whereas OCF 3.29 +/- 0.80 ml/min X g was nearly unchanged (control 3.59 +/- 0.85). The ratio OCF/ICF was increased to 1.37 (1.11). Further dehydration by hypertonic peritoneal dialysis for 3 h increased Hct to 60 +/- 4 and further reduced OCF and ICF, without significant change of the OCF/ICF-ratio. At Hct above 55 sudden and intermittent changes in local cortical blood flow were recorded randomly at individual electrode sites, showing ischemic periods lasting for 1 to 60 min. Such flow changes were observed in 13 of 14 expts. and were not accompanied by changes in RBF. It is concluded that moderate dehydration causes a greater reduction of ICF than of OCF. Severe dehydration gives in addition rise to patchy, intermittent ischemia in both cortical layers.