Atrial natriuresis under the condition of a constant renal perfusion pressure

An experimental elevation of left atrial pressure (eLAP ↑) by means of a reversible mitral stenosis is accompanied with an increase in sodium excretion (UNa—) and arterial blood pressure (by about 20 mm Hg, 2.7 kPa), and by a decrease in plasma renin activity. It is well established that an increase in renal perfusion pressure (Pren) can augment UNa—. Therefore the present study was undertaken to examine whether the eLAP ↑-induced natriuresis was caused by the increased Pren. — Four female beagle dogs were kept under controlled environmental conditions. They received asodium rich diet (14.5 mmol/Na/kg/d). The dogs were chronically instrumented: purse string around the mitral annulus, catheter in the left atrium, carotid loop, pneumatic cuff above the renal arteries, pressure transducer below the renal arteries. Pren was kept constant by means of a digital servofeedback control circuit. The dogs served as their own controls (13 experiments without and 15 experiments with a controlled renal perfusion pressure were performed). After eLAP↑(+1.0 kPa), UNa— rose from 4.1±2.6 to 10.3±3.9 μmol Na/min/kg. If Pren was kept constant, the corresponding values were 4.2±2.8 and 9.3±2.9 μmol/min/kg. These data clearly indicate that the atrial natriuresis is not mediated by an augmentation of renal perfusion pressure. Therefore these results support the hypothesis that atrial natriuresis probably is due to an eLAP↑-induced suppression of the renin-angiotensin-system or other natriuretic mechanisms.     

No relation between atrial natriuresis and renal blood flow in conscious dogs

Summary Conscious dogs were used to study whether changes in total renal hemodynamics are responsible for diuresis and natriuresis during an experimental increase in left atrial pressure (LAP). To ensure a controlled dietary sodium intake, the dogs (n=8) were chronically kept on ahigh or alow sodium intake diet (HSI; LSI). After the dogs had completely recovered from surgery (carotid loop, thoracotomy, flank incision), LAP was increased by about 10 cm H₂O for 60 min by tightening a purse string around the mitral annulus (51 expts). Mean urine volume (V) increased in both groups to a comparable degree. Mean sodium excretion increased somewhat more in HSI dogs, but remained elevated in LSI dogs after the LAP increase. Renal blood flow (electromagnetic flow transducer) and inulin clearance did not change. Renal vascular resistance (RVR) increased by about 20% (HSI) and 15% (LSI). — When the induced LAP increase was terminated, V decreased. RVR decreased in HSI dogs by about –11% and in LSI dogs by about –6% below control values.—It is concluded that volume regulatory mechanisms induced by an experimental LAP increase operate independently of changes in total renal blood flow.The Arbeitsgruppe Experimentelle Anästhesie is member of the Research Group Autonomic Regulations Freie Universität Berlin     

Left atrial pressure and postprandial diuresis in conscious dogs on a high sodium intake

Summary 5 conscious, well trained, female dogs kept on a high sodium intake (14 meq Na/kg bw) were used to measureeft atrial pressure (LAP), urine volume ( ), sodium and potassium excretion (U_Na , U_K ) as well as plasma osmolality (P_osm) before and up to 180 minafter food intake. The dogs were fitted with a catheter in the left atrium (thoracotomy). In all experiments (n=23) LAP increased postprandially (pp) above fasting controls. The mean peak increase range from 4 to 6 cm H₂O and was observed as early as 61–80 and as late, as 161–180 min pp. Increase in LAP was closely correlated to V which rose from 36±28 to 160±51 ul/min·kg. pp was also correlated to pp U_Na which increased from 4.8±3.3 to 34.0±8.5 ueq/min·kg.The pp increase in LAP and its close relation to pp and pp U_Na emphasize the assumption that intrathoracic receptors are involved in the regulation of body fluids.     

Left atrial pressure and sodium balance in conscious dogs on a low sodium intake

Summary 10 conscious chronically prepared dogs were used. After recovery from thoracotomy (catheter into the left atrium, nylon purse string around the mitral annulus) they were kept chronically on a low sodium intake (<0.5 meq Na/kg bw daily). On 51 days left atrial pressure (LAP) was increased for 60 min about 10 cm H₂O once daily by tightening the purse string (distension period: DP).During DP urine volume ( ) increased about threefold, and sodium excretion (E _Na) about sixfold. The amount of renal sodium loss on the days when LAP was increased exceeded the daily intake considerably. The application of DOCA (15 mg i.m.) did not diminishE _Na during DP and 60 min thereafter. During DP heart rate increased by about 70 b/min and mean arterial blood pressure increased by about 15 mm Hg.The data suggest that stimulation of intrathoracic receptors by a reversible mitral stenosis augments renal sodium excretion even in a state of a highly stimulated tubular sodium resorption.Preliminary reports of parts of this work have been presented at the meetings of the Deutsche Physiologische Gesellschaft in Bochum (1975) and Wien (1975). The authors are indebted to Dr. Üdes and Dr. Nebendahl for the invaluable veterinary assistance and to Mrs. Jäckel and Mrs. Mohr for technical assistance. Dr. Eisele is surgeon at the Schloßparkklinik, BerlinThe AG Experimentelle Anaesthesie is member of the Research Group Autonomic Regulations, FU Berlin     

Atrial pressure and postprandial volume regulation in conscious dogs

Conscious, chronically instrumented dogs (n=24; left and right atrial catheter, electromagnetic flow probe around the left renal artery, carotid loop) were used in 97 expts. to study mechanisms mediating postprandial (pp) excretion of sodium and water up to at least 180 min after food intake. The dogs were kept under standardized conditions and maintained on ahigh (14.5 mmol Na/kg b.w./day) or alow (0.5 mmol Na/kg b.w./day) sodium intake diet (HSI, LSI) which was given once daily in the morning.In HSI dogs left atrial pressure (LAP) increased from a fasting control value of 0.2 kPa (2 cm H₂O) to 0.7 kPa (7 cm H₂O) (120–180 min pp), right atrial pressure from 0.0 kPa (0 cm H₂O) to 0.3 kPa (3 cm H₂O). 25% of the sodium intake were excreted up to 180 min pp. There was a highly significant positive correlation between pp sodium excretion (U _Na V) and pp LAP.U _Na V was not related to pp increase in renal blood flow (RBF) and glomerular filtration rate (GFR). Fractional sodium excretion increased from a fasting control value of 0.6% to more than 4% in HSI dogs and from 3.3% to more than 7% in anadrenalectomized HSI dog. DOCA did not diminishU _NA V in HSI dogs.In LSI dogs, RBF and GFR increased pp, LAP did not change pp. No substantial increase inU _Na V was observed.The close correlation between ppU _Na V and pp LAP in HSI dogs supports the hypothesis that intrathoracic vascular receptors are involved in the mediation of volume regulation by stimulation of still unknown natriuretic mechanisms which operate on the tubular level in the presence of high mineralocorticoid activity.     

Effect of noradrenaline on tail arteries of SHR and WKY under perfusion at constant flow and constant pressure

Vasoconstrictor effects of noradrenaline were compared in 6- to 7-month-old spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats. A cylindrical segment was dissected from the proximal part of tail artery, cannulated at both ends and perfused alternately either at constant flow or constant pressure. Two series of experiments were performed. In the first series, vessels were perfused/superfused with Krebs-Henseleit solution. In the second one a modified salt solution was used, in which NaCl was totally replaced by an equimolar amount of KCl. Under constant flow conditions noradrenaline evoked a more prominent resistance increase in SHR compared with WKY independently of the composition of solution (normal or high-K⁺) used. At constant pressure perfusion with normal solution, the vasoconstrictor response to noradrenaline was more prominent in WKY. Under application of high-K⁺ solution, vasoconstriction at constant pressure in SHR became more pronounced than that in WKY. We suggest that there is greater wall thickness:lumen diameter ratio in SHR vessels and thus different contribution of distension-activated myogenic response is of primary importance for the data obtained.     

Influence of renal nerves on renin secretion in the conscious dog

In order to evaluate the influence of renal nerves on renin secretion during changes in blood volume, we studied the mean arterial blood pressure (MAP) and the renal venous plasma renin activity (PRA) in 6 conscious dogs having one intact and one denervated kidney.After a passive head-up tilt PRA increased significantly in the vein of the intact kidney while it remained stable in the denervated one.The intravenous injection of Furosemide (3 mg/kg) induced a rapid elevation of PRA in both renal veins. The kinetics of the variations of renin secretion were similar in the two kidneys, but its magnitude was significantly lower in the denervated side.After a slow hemorrhage of 2, 4 and 6 ml/kg, MAP was unchanged and PRA increased in both renal veins but in a significantly lower degree in the denervated side. When blood loss reached 8 ml/kg, MAP decreased and PRA increased identically in the two renal veins.It was concluded that, in conscious dogs, the renal nerves could participate in the rapid adaptations of renin secretion during small changes in the circulating blood volume.     

A servo-controlled roller pump for constant flow or constant pressure blood perfusion under normal pulsatile or non-pulsatile conditions

This paper describes the design of a servo-controlled precision roller pump applicable for constant blood flow or constant blood pressure perfusion in research on the peripheral circulation. The pump, and its feed-back control, can simulate normal cardiac induced autoperfusion by reproducing the arterial pulse pressure configuration with high fidelity. Its design is such as to minimize damage of the red blood cells and consequent release of vasoactive substances, a problem encountered with most conventional pumps. The present pump principle may also find a use in heart-lung machines and dialysis equipment and can be used as a precision infusion pump.     

Interrelationships between sodium clearance,plasma aldosterone,plasma renin activity,renal hemodynamics and blood pressure in renal disease

Summary This study was designed to evaluate the role of aldosterone, glomerular filtration and blood pressure on sodium excretion in renal disease. Sodium clearance (C_Na), plasma aldosterone (PA), plasma renin activity (PRA), glomerular filtration rate (GF), paraaminohippurate clearance (C_PAH) and blood pressure were measured simultaneously in 19 normal subjects, 38 patients with benign essential hypertension, 3 with renal artery stenosis, 48 with chronic glomerulonephritis, 20 with the nephrotic syndrome, 24 with tubulo-interstitial disease and 21 with a renal homograft.C_Na was significantly depressed in patients with the nephrotic syndrome. Mean PA and PRA were increased in renal artery stenosis, but within the normal range in the other groups. C_Na correlated inversely with PA in all groups but one (tubulo-interstitial disease). C_Na correlated directly with GF in the nephrotic syndrome and with the mean blood pressure (mBP) in chronic glomerulonephritis and tubulointerstitial disease. PA correlated directly with PRA and inversely with GF or C_PAH in most groups.It is concluded that PA is an important determinant of the basal natriuresis in renal disease with the exception of tubulo-interstitial nephropathies. In the nephrotic syndrome sodium retention is largely determined by the interaction of PA and GF. In chronic nephropathies, but not in benign essential hypertension, the fractional sodium excretion is partly blood pressure-dependent. Impairment of renal function is often accompanied by a rise in PA.     

Effect of splanchnicotomy on the renal excretion of uric acid in anaesthetzed dogs

Summary The renal excretion of uric acid was examined during acute i.v. urate (Ua) loading on unilaterally splanchnicotomized (renal denervation) anaesthetize mongrel dogs. Glomerular filtration rate (GFR) in general was not different in innervated and denervated kidneys, whereas urine flow (V) and urinary excretion of sodium (U_NaV) on the splanchnicotomized side were significantly increased at any plasma concentration of Ua. The excretion (U_UaV) and tubular transport (T_Ua) of urate calculated for unit GFR were considerably increased and depressed, respectively, at normal plasma Ua level and during minor urate loading (plasma concentration up to 4.7 mg%). Above this plasma level, i.e. up to 24.6 mg%, no difference in net urate reabsorption between intact and sympathectomized organs was found. It is suggested that both reabsorption and secretion of Ua in denervated kidneys are diminished.     

The reflex effect of changes in renal perfusion on hindlimb vascular resistance in anaesthetized rabbits

This study was designed to characterise the response of the hindlimb vasculature to reduced renal perfusion in the anaesthetized rabbit and to elucidate whether the stimulus was dependent upon reduced renal perfusion pressure (RPP) or blood flow (RBF). Acute decreases in renal perfusion resulted in rapid and reversible increases in femoral perfusion (FPP). This vascular response was completely abolished following renal denervation indicating that the afferent component of the reflex is neurally mediated. Acute hindlimb responses to changes in renal perfusion pressure were present whether the limb was perfused with homologous blood or cross-perfused with blood from a donor rabbit, demonstrating that the efferent component of the response is also neurally mediated. There was a 28-s latency for initiation of the hindlimb vasoconstriction, which is consistent with recent evidence for renal autocoid stimulation of the afferent renal nerve receptors. Decreasing RPP indirectly, by altering flow, resulted in a hindlimb vasoconstriction below approximately 55 mm Hg (7.3 kPa) RPP or 15 ml/ min RBF. However, decreasing RPP by directly reducing pressure in graded steps resulted in increases in FPP, which reflected the changes in renal flow; thus during the autoregulatory phase, where flow did not change as pressure fell, FPP also remained stable. The results of these protocols suggest that a neurally mediated hindlimb vascular reflex is stimulated by decreased renal flow rather than pressure.     

Effect of splanchnicotomy on the renal excretion ofd-glucose in the anaesthetized dog

Summary The effects of acute intravenousd-glucose (G) loading were studied on anaesthetized, unilaterally splanchnicotomized (renal denervation) dogs. Glomerular filtration rate (GFR) was generally not different on the innervated and denervated side, while urine flow (V), sodium excretion (U_NaV) and urinary excretion (U_GV) of glucose on the splanchnicotomized side were significantly increased at any plasma G concentration. Tubular reabsorption (T_G) as well as Tm of G in denervated kidneys was considerably depressed. In a series of experiments with moderately elevated plasma glucose level glucosuria on the sympathectomized side was found that seems to be the consequence of a lower threshold for G in denervated kidneys. The positive correlation between the tubular reabsorption of Na and G was not influenced by renal denervation.     

Effects of bilateral carotid occlusion and auditory stimulation on renal blood flow and sympathetic nerve activity in the conscious dog

In conscious foxhounds with intact aortic baroreceptors the effects of common carotid occlusion (C. C. O.; 3 dogs) or excitement (elicited by a sudden loud noise due to firing a pistol; 7 dogs) on renal blood flow (R.B.F.) were studied. C.C.O. increased arterial blood pressure by 40–50 mm Hg and heart rate by 22 beats/min while R.B.F. remained unchanged. When kidney perfusion pressure was maintained during C.C.O. there was also no change in R.B.F. Excitement increased mean aortic blood pressure by 35 mm Hg and heart rate by 84 beats/min; R.B.F. was transiently reduced by 40% of control.In another 3 foxhounds successful recordings of renal sympathetic nerve activity (R.S.N.A.) were obtained in the conscious state for 2–7 postoperative days. The effects of C.C.O. or excitement — elicited by whistling or hand-clapping — on R.S.N.A. were tested. There was pulse-synchronous nerve activity in the resting conscious animal. C.C.O. induced a steady state increase of averaged R.S.N.A. by 62% of control. Excitement was associated with transient bursts of activation of averaged R.S.N.A. by 500% of control.It is concluded that total R.B.F. is not changed during the baroreceptor short-term adjustment of blood pressure although changes in sympathetic outflow to the kidney are observed under comparable conditions. In contrast, excitement causes a much higher degree of sympathetic activation; this is probably responsible for the intense, transient renal vasoconstriction.This study was supported by the German Research Foundation within the S.F.B. 90 Heidelberg     

The influence of long-term infusion of the calcium antagonist diltiazem on postischemic acute renal failure in conscious dogs

Summary The influence of long-term infusion of the calcium-entry blocker diltiazem on postischemic acute renal failure was investigated in conscious dogs monitored by implanted instruments. In 18 uninephrectomized beagle dogs on a salt-rich diet, an electromagnetic flow probe and an inflatable plastic cuff were placed around the renal artery. Acute renal failure was induced by inflating the cuff for 180 min in the conscious animal. Group A (n=5, control) received an intraaortic injection of 0.9% NaCl (5 ml/day) from the 3rd day before until the 7th day after ischemia and group B (n=6, posttreatment) an intra-aortic injection of diltizem (5 µg·min^–1·kg^–1) beginning at the end of ischemia until the 7th day. Group C (n=7, pre- and posttreatment) received diltiazem from the 3rd day before until the 7th day after ischemia. In group A, renal blood flow dropped from 149±16 (preischemic) to 129±29 ml·min^–1 on the 1st day after ischemia. In contrast, renal blood flow increased on the 1st postischemic day in both treatment groups by 29±15% (group B,P 0.05) and 14±13% (group C). In the following days, there was no significant difference in renal blood flow between groups A, B and C. In group B, the reduction of the glomerular filtration rate was similar to that in the control group. In group C, the glomerular filtration rate was significantly less reduced than in group A (34±1.8 preischemically to 17±5.4 on day 1,P 0.05 and 20±4.1 ml·min^–1 on day 7,P 0.05). Plasma renin activity increased in both diltiazem groups, more pronounced so in group B (from 3.7±1.0 on day 1 to 16.2±7.9 ng ATI·ml^–1·h^–1 on day 7,P 0.05). In contrast to groups A and B, the increase in fractional sodium excretion was less pronounced in group C. Likewise, the decrease in free water-reabsorption was less marked than in groups A or B. It was apparent that diltiazem, when administered pre- and post-ischemically, preserved glomerular filtration rate and renal blood flow. When diltizem was given solely postischemically there was an improvement in renal blood flow, but no significant influence on glomerular filtration rate. We therefore conclude that mainly tubular factors, in addition to the attenuation of postischemic vasoconstriction, are involved in the protective effect of diltiazem on postischemic acute renal failure in conscious dogs.Abbreviations ARF acute renal failure - C_osmol clearance of osmolarity - E_Na urinary excretion rate of sodium - FE_Na fractional excretion rate of sodium - GFR glomerular filtration rate - HR heart rate - NE norepinephrine - PAM mean arterial blood pressure - PRA plasma renin activity - RBF renal blood flow - RVR renal vascular resistance - T_H2_O free water reabsorption - V_U urine volume     

The effect of renal perfusion pressure on renal vascular resistance in the spontaneously hypertensive rat

Renal hemodynamics and renal vascular resistance (RVR) were measured in the spontaneously hypertensive rat (SHR) and in the normotensive Wistar-Kyoto rat (WKY). In addition, the autoregulatory response and segmental RVR in the SHR were studied after aortic constriction. Mean arterial pressure (MAP) and RVR were higher in the SHR than in the WKY, but renal blood flow (RBF) and glomerular filtration rate were similar in both groups. Measurement of mean afferent arteriolar diameter (AAD) by a microsphere method showed a significantly smaller AAD in SHR (17.7±0.35 m) than in the WKY (19.5±0.20 m). This decrease in AAD could account for a 47% increase in preglomerular resistance. Aortic constriction in the SHR, sufficient to reduce renal perfusion pressure from 152 to 115 mm Hg, did not alter the AAD. Since RBF and glomerular filtration were also well maintained following aortic constriction, these autoregulatory responses suggest that vessels proximal to the afferent arteriole rather than postglomerular vasculature are primarily involved in the changes on intrarenal vascular resistance in SHR.     

Continuous perfusion under pressure using several tubes in the freely behaving rat

The technique described allows connecting several tubes and electric wires to a rat, leaving the latter free to move. The principle of the technique is the twisting of the tubes and electric wires together to form a helix. This converts torsional stresses on tubes and wires into longitudinal stresses.     

Effect of splanchnicotomy on the renal excretion of para-aminohippuric acid in the anaesthetized dog

Summary Renal excretion of para-aminohippuric acid (PAH) was studied during PAH loading on unilaterally splanchnicotomized (denervated) anaesthetized dogs. Urine flow, sodium excretion of denervated kidneys were significantly increased. Below a plasma concentration of 20 mg% there were no differences between intact and denervated kidneys in urinary excretion and in calculated tubular transport of PAH. However, maximum secretion rate on the splanchnicotomized side was significantly decreased (innervated: 34.8, denervated: 25.2 mg/100 ml GFR, respectively). Although both Na reabsorption and PAH secretion are impaired by denervation, the exact mechanism of action of renal sympathectomy is not elucidated as yet.     

不阻断肾动脉左肾静脉移位术治疗胡桃夹综合征的临床疗效观察

目的 探讨不阻断肾动脉左肾静脉移位术治疗胡桃夹综合征的临床疗效。方法 回顾性分析山东省立第三医院泌尿外科1999年1月—2017年1月收治的10例胡桃夹综合征患者的临床资料(手术组),男8例、女2例,年龄22~53(39.9±10.5)岁,均行不阻断肾动脉左肾静脉移位术;观察手术时间、术中出血量、肾静脉阻断时间、术后引流量、拔管时间、血尿消失时间;比较手术组患者手术前后站立位和平卧位时的左肾静脉狭窄段与扩张段血管管径及血流速度。随机选取2016年7月健康管理中心体检已排除肾脏疾病的10名健康成人(对照组),男5例、女5例,年龄21~45(37.0±5.8)岁;比较手术组术后与对照组的左肾静脉血管管径、血流速度。结果 手术组10例患者手术时间(171.0±10.8)min,术中出血量(138.0±42.1)mL,肾静脉阻断时间(9.5±1.3)min,术后引流(130.0±24.5)mL,拔管时间(3.3±0.8)d,肉眼血尿消失时间为(4.2±1.2)d,镜下血尿消失时间为(7.3±1.1)d。术后随访2~6个月,平均3个月。患者术后均无血尿、蛋白尿,左肾静脉狭窄段内径较术前增加、血流速度较术前下降。比较不同体位下左肾静脉狭窄段与扩张段内径及血流速度,手术组患者术前差异均有统计学意义(P值均＜0.01),术后末次随访差异均无统计学意义(P值均＞0.05);手术组患者术后站立位左肾静脉狭窄段内径及血流速度与对照组比较,差异均无统计学意义(P值均＞0.05)。结论 不阻断肾动脉的左肾静脉移位术治疗胡桃夹综合征疗效较好。     

Sympathetic modulation of renal hemodynamics,renin release and sodium excretion

Summary In anesthetized animals it has been shown previously, that the influence of electrical stimulation of efferent renal nerves on renal function with increasing stimulation frequencies can be graded; renin release is affected at low, sodium excretion at intermediate and vascular resistance at high stimulation frequencies.Experiments in conscious dogs are reviewed, which present evidence for a similar functional dissociation under physiological conditions.Moderate activations of the renal sympathetic nerves, which do not change renal blood flow 1) decrease sodium excretion independent of changes in angiotensin II, 2) interact with the pressure-dependent mechanism of renin release by resetting its threshold pressure and 3) modulate autoregulation by increasing the lower limits of glomerular filtration rate and renal blood flow-autoregulation.These findings may contribute to our understanding of the role of the renal nerves in the pathophysiology of congestive heart failure and hypertension.     

Examination of possible renal origin of the humoral factor responsible for saline diuresis in the dog

Summary The hypothesis of renal origin of the humoral factor responsible for the natriuresis which follows saline infusion in the dog was tested in a cross-circulation model especially designed for the purpose. Renal venous blood of saline loaded donor dogs was pumped directly into the system perfusing the right (assay) kidney of oliguric recipient animals. In control and recovery periods, recipients own renal venous blood was substituted for the blood of saline-infused donors.Sodium excretion increased slightly from the control value of 2.8±1.2 (S.D.) to 4.7±3.5 Eq/min (68 per cent increase,p<0.05), but only slight recovery toward control rate was noted within 25 min of cessation of cross-circulation. Simultaneously, filtered sodium decreased slightly from 2.8±1.15 (S.D.) to 2.7±1.10 mEq/min. Glomerular filtration rate (C _CR) and effective renal plasma flow (C _PAH) decreased gradually during the experiment. Urine flow,U/P _osm, hematocrit, and perfusion pressure of the assay kidney showed only minor changes.Since the slight increase in sodium excretion during cross-circulation constituted but a small fraction of natriuresis observed in saline-loaded donors, it was concluded that the results are incompatible with the release from the kidney of saline-infused animals of a potent natriuretic factor.This study was supported by American Heart Association Grant 66630.