Fall In Renal Blood Flow Research Articles

Renal Blood Flow and Glomerular Filtration Rate during the Heterologous Phase in Passive Heymann Nephritis in Rats

When passive Heymann nephritis (PHN) is induced by infusion of antibodies (anti-Fx1A), an acute fall in renal blood flow (RBF) and glomerular filtration rate (GFR) has been reported. Activation of the complement cascade by the local antigen-antibody reaction might be involved in this reaction. We therefore studied RBF and GFR during acute infusion of anti-Fx1A and after 3 days when heterologous antibodies are no longer present in the circulation. Two groups of rats were infused with 2 mg anti-Fx1A antibodies into the left renal artery; RBF was measured by the microsphere method and GFR by 125I-Na-iothalamate clearance. In the first group, the measurements were made 40 min after the infusion, and in the second group after 3 days. A third group was studied 3 days after infusion of 1 mg anti-Fx1A. Animals infused with normal IgG were used as controls. Forty minutes after infusion of 2 mg anti-Fx1A, GFR in the left kidney was reduced from 1.16 +/- 0.07 to 0.41 +/- 0.16 ml/min/g in the controls (p less than 0.05). Three days after the infusion, GFR was 1.04 +/- 0.07, not significantly different from control. RBF was reduced to 3.97 +/- 1.11 ml/min/g after 40 min, compared to 7.53 +/- 0.73 in controls (p less than 0.05), and was normalized after 3 days. The effect of 1 and 2 mg anti-Fx1A antibodies was not significantly different after 3 days. Anti-Fx1A antibodies were detected in serum in the acute stage, but not after 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Neuropeptide Y on Cardiac Performance and Renal Blood Flow in Conscious Normotensive and Renal Hypertensive Rabbits

The effects of neuropeptide Y (NPY, 10 micrograms/kg bolus iv) on cardiac output, renal blood flow and myocardial contractility were determined in intact renal hypertensive and normotensive rabbits instrumented with ultrasonic flow transducers or left ventricular catheters. The basal plasma concentration of NPY-like immunoreactivity in arterial blood was greater in the hypertensive rabbits (4.2 +/- 0.7 micrograms/l) than in normotensive animals (2.2 +/- 0.4 micrograms/l, p less than 0.05). There were similar moderate increases in arterial blood pressure and total peripheral resistance following NPY, but a small NPY-induced reduction in cardiac output in normotensive rabbits was not seen in hypertensive animals. Resting peak left ventricular dP/dt (an index of myocardial contractility) was higher in hypertensive rabbits (7397 +/- 619 vs 5551 +/- 342 mmHg/sec, p less than 0.05), but there was no significant difference between the maximum NPY-induced falls in peak dP/dt. NPY produced significant peak reductions in renal blood flow in both hypertensive (from 2.5 +/- 0.2 to 1.2 +/- 0.2 kHz, p less than 0.05) and in normotensive rabbit groups (from 2.2 +/- 0.1 to 0.3 +/- 0.1 kHz, p less than 0.05), but the fall in renal blood flow and the corresponding rise in renovascular resistance were smaller in the hypertensive animals (p less than 0.05). The cause of this apparent decrease in renovascular reactivity in the renal hypertensive model was not determined.

Interaction of Prostaglandins and Angiotensin II in the Modulation of Renal Function in Congestive Heart Failure

Despite a dramatic fall in renal blood flow, glomerular filtration rate is usually preserved in patients with congestive heart failure until the terminal stages of the disease. This maintenance of renal function appears to be achieved in part by the synthesis of two vasoactive factors within the kidney--angiotensin II and prostaglandins--which are rapidly released whenever renal perfusion is compromised or sympathetic nerve traffic to the kidneys is increased. Although these two hormonal systems exert opposite effects on systemic and renal blood flow and sodium and water excretion, both act to preserve glomerular filtration rate: prostaglandins by a vasodilator action exerted primarily on the afferent arteriole and angiotensin II by a vasoconstrictor effect on the efferent arteriole. Consequently, when the synthesis of these hormones is experimentally blocked, renal function deteriorates, especially in subjects with marked renal hypoperfusion and sodium depletion; these two factors interact to determine the importance of intrarenal hormonal release in the modulation of renal function. Clinically, four specific factors have been identified that predispose patients with heart failure to the development of functional renal insufficiency after treatment with converting-enzyme or cyclo-oxygenase inhibitors: (1) marked renal hypoperfusion, (2) vigorous diuretic therapy, (3) diabetes mellitus, and (4) intensity of hormonal inhibition within the kidney. This last risk factor may provide the basis for differentiating among enzyme-inhibitory drugs and suggests that renal insufficiency in low-output states may be minimized by the development of therapeutic agents that block hormonal synthesis selectively at sites that are critical to the disease process but spare the homeostatic tissue-based enzyme systems that exist within the kidney.

Early metabolic effects of hypotension on rat kidney.

Saturation-transfer phosphorus nuclear magnetic resonance (STNMR) has been applied to the rat kidney in vivo. The rate of renal metabolism determined by this method compares favorably with the renal oxygen consumption, assuming an ATP:oxygen ratio of 2. Hemorrhagic hypotension resulted in a 20% fall in renal blood flow and a significant fall in oxygen consumption. The rate of renal metabolism fell by 50%. This rate of ATP synthesis was below that required to maintain a normal [ATP], but renal [Pi] was not increased. When renal perfusion was reduced by 60%, intrarenal [Pi] rose. When [P1] was elevated, the method os STNMR no longer gave a reliable measure of the rate ATP synthesis, indicating that this new Pi pool was not in rapid chemical exchange with ATP. STNMR represents a useful noninvasive means of monitoring renal metabolic rate, with limitations due to insensitivity and the existence of multiple pools of intrarenal Pi.

Renal haemodynamics during hyperchloraemia in the anaesthetized dog: effects of captopril.

1. An increase in plasma chloride concentration (PC1) decreases renal blood flow (RBF) and glomerular filtration rate (GFR) and inhibits the intrarenal release of renin and angiotensin II (AII). Captopril was administered to indomethacin-treated dogs to assess the role of AII independent of prostaglandins (PGs) in the haemodynamic response to hyperchloraemia. Studies were performed on kidneys that were denervated by autotransplantation. 2. Anaesthetized greyhounds received an intrarenal infusion of 0.616 M-sodium acetate, which was changed to 0.616 M-NaCl (hyperchloraemia). These infusions increased the plasma sodium and osmolality at the experimental kidney by 7-11% throughout but increased the PCl during the hypertonic NaCl infusions only (122 +/- 3 to 136 +/- 3 mM). 3. In vehicle-treated dogs (n = 8), hyperchloraemia reduced the GFR (1.4 +/- 0.1 to 1.0 +/- 0.1 ml min-1 kg-1; P less than 0.05) and the RBF (13.0 +/- 1.4 to 8.3 +/- 0.6 ml min-1 kg-1; P less than 0.01); these changes were reversible on return to the 0.616 M-sodium acetate infusion. Hyperchloraemia reduced the release of AII into renal lymph (2.5 +/- 0.9 to 1.2 +/- 0.4 pg min-1 kg-1; P less than 0.01). 4. Indomethacin (0.6 mg kg-1 and 0.2 mg kg-1 h-1 intrarenally; n = 4) blunted (P less than 0.05) the Cl--induced fall in RBF (10.4 +/- 1.1 to 8.2 +/- 0.6 ml min-1 kg-1) without changing significantly the fall in GFR or the release of AII into renal lymph.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of leukotriene D4 on glomerular dynamics in the rat.

Glomerular micropuncture studies were performed in euvolemic, anesthetized, adult, male Munich-Wistar rats to evaluate the glomerular microcirculatory actions of leukotriene D4 (LTD4). In preliminary experiments, intrarenal arterial administration of LTD4 (1 microgram X kg-1 X min-1) was found to cause a rise in mean systemic arterial pressure, a loss of plasma volume, and a fall in renal blood flow, effects identical to those previously reported for LTC4. To assess the local glomerular actions of LTD4 independently of these systemic effects, glomerular microcirculatory dynamics were assessed during LTD4 infusion while constancy of renal perfusion pressure and plasma volume were maintained by partial aortic constriction and isoncotic plasma infusion, respectively. To ascertain the LTD4 actions that are independent of angiotensin II, saralasin (5 micrograms X kg-1 X min-1 iv) was also given throughout the study. LTD4 caused a significant increase in efferent arteriolar resistance in association with a fall in glomerular plasma flow rate (QA) and a rise in glomerular capillary hydraulic pressure. Despite the latter, single-nephron filtration rate fell due to combined reductions in QA and the glomerular ultrafiltration coefficient. These local glomerular constrictor actions of LTD4 support the possibility that this eicosanoid might play an important intermediary role in the functional impairment accompanying some forms of inflammatory injury.

Renal effects of theophylline and caffeine in newborn rabbits.

Renal hemodynamics and functions were assessed in four groups of anaesthetized newborn rabbits receiving a single intravenous dose of methylxanthines, i.e.: aminophylline: 3 mg/kg (A1) or 6 mg/kg (A2); sodium benzoate caffeine: 5 mg/kg (C1) or 10 mg/kg (C2). Each animal acted as its own control. The mean PAH extraction ratio was not modified by the methylxanthines. Renal blood flow and glomerular filtration rate were determined by clearances of para-aminohippuric acid and inulin, respectively. No changes in renal hemodynamics or renal functions were observed in group C1. In group C2, renal blood flow and filtration fraction did not vary significantly but renal vascular resistance showed a delayed increase. Systemic infusion of the two aminophylline regimens induced a delayed increase in renal vascular resistance with a concomitant fall in renal blood flow and an increase of filtration fraction in group A2. Glomerular filtration rate was either reduced (3 mg/kg aminophylline) or increased (6 mg/kg aminophylline and 10 mg/kg caffeine). Moreover, diuresis increased and tubular water reabsorption declined in groups A1, A2, and C2. High dose caffeine enhanced sodium fractional excretion. The acute renal effects of methylxanthines appeared dose- and time-related in immature animals and caffeine proved safer than aminophylline at doses used in human neonates.

Influence of Vasoactive Substances on Early Toxic Acute Renal Failure in the Dog

The influence of different vasoactive substances on the evolution of HgCl2-induced acute renal failure (ARF) was evaluated in the dog. HgCl2 alone caused a progressive fall in both glomerular filtration (GFR) and renal blood flow (RBF) during the first 3 h of the mercury administration (delta after 3 h: -44% and -39%) and provoked a concomitant stimulation of the renin-angiotensin (RAS) and thromboxane systems. The administration of the thromboxane inhibitor dazoxiben (2 mg/kg i.v. every 2 h) adequately inhibited the activation of the thromboxane system after HgCl2, but could not prevent the fall in GFR and RBF. The continuous intrarenal administration of the Ca2+ entry blocker verapamil (0.005 mg/kg per min) into the left kidney resulted in the prevention of the postmercurial fall in GFR and RBF at the perfusion site. This beneficial effect was immediately lost when the verapamil administration was stopped. Finally, the administration of the converting enzyme inhibitor captopril (300 micrograms/kg every 2 h) resulted in an effective inhibition of the renin-angiotensin system, the prevention of the postmercurial fall in RBF, and the partial attenuation of the fall in GFR. This beneficial effect was immediately lost after the intravenous administration of indomethacin (2 mg/kg). These results indicate that the fall in GFR after HgCl2 can be prevented by vasoactive agents such as captopril and verapamil and point at least in part to a pathophysiological role of the renin-angiotensin system or of an alteration in the equilibrium between renin-angiotensin and prostaglandins. The thromboxane system is seemingly of no major importance.

Oestrogen-induced changes in renal haemodynamics in the rat: influence of plasma and intrarenal renin.

The effect of oestrone acetate (in total doses of 5 and 10 mg) on systemic and renal haemodynamics and the renin-angiotensin system has been studied in adult female rats. The administration of 10 mg of oestrogen resulted in a significant fall in renal blood flow associated with significant rises in both renal vascular resistance and mean arterial pressure. No changes were noted in cardiac output or total peripheral resistance at either dose. Whilst the higher dose of oestrogen induced a significant increase in plasma renin activity, no change was noted in animals receiving 5 mg of oestrogen. Both regimens caused significant reductions in plasma and intrarenal renin concentrations. Although renal blood flow correlated with plasma renin activity in animals with a normal renal blood flow, no such correlation was noted in animals with oestrogen-induced reductions in renal blood flow. The present study demonstrates that oestrogen-induced reductions in renal blood flow result from a rise in intrarenal vascular resistance which cannot be accounted for by simultaneous changes in either plasma renin activity or renal renin concentration.

Selective Inhibition of Thromboxane Synthesis in Glycerol-Induced Acute Renal Failure

It has recently been postulated that thromboxane A2 may participate in the pathogenesis of acute myohemoglobinuric experimental acute renal failure. To investigate this further, the effect of selective inhibition of thromboxane synthesis on the course of glycerol-induced acute renal failure was determined. Despite significant inhibition of thromboxane synthesis by 4-imidazole-yl-acetophenone, the functional and morphologic disturbance induced by glycerol was unaltered. Moreover, pretreatment with 4-imidazole-yl-acetophenone failed to prevent the fall in renal blood flow seen following glycerol administration. These results argue against a major role for thromboxane A2 in the pathogenesis of this form of experimental acute renal failure.

Evidence of prostacyclin deficiency in the syndrome of hyporeninemic hypoaldosteronism.

Hyporeninemic hypoaldosteronism is an important cause of hyperkalemia and is characterized by low renin secretion. We found that prostacyclin, a potent vasodilator and renin secretagogue, was markedly reduced--as reflected by its stable urinary metabolite 6-keto-prostaglandin F1 alpha--in seven patients with hyporeninemic hypoaldosteronism as compared with seven matched controls with renal insufficiency and as compared with 12 normal volunteers (mean +/- SE, 42 +/- 7 vs. 185 +/- 37 and 164 +/- 20 ng per gram of creatinine, respectively; P less than 0.001). In contrast, renal prostaglandin E2 excretion was similar in all three groups. A low-dose infusion of calcium or norepinephrine (known stimulants of prostacyclin) increased renal prostacyclin release in normal subjects and controls with renal insufficiency. Neither agonist, however, increased the low basal prostacyclin excretion in the patients (49.6 +/- 11 [basal] vs. 62 +/- 20 [norepinephrine] and 47.5 +/- 16 [calcium]; P greater than 0.8). To evaluate the functional importance of the altered prostacyclin production, we studied the responses of renal blood flow and blood pressure to the calcium infusion. The calcium infusion did not alter blood pressure or renal blood flow in the normal subjects or the controls with renal insufficiency. In contrast, the same dose of calcium in the patients with hyporeninemic hypoaldosteronism produced a rise in mean blood pressure (from 91 +/- 6 to 104 +/- 8 mm Hg, P less than 0.05) and a fall in renal blood flow (from 673 +/- 58 to 560 +/- 42 ml per minute per 1.73 m2, P less than 0.05). These results indicate that a deficiency of prostacyclin could explain the low active-renin concentration and altered vasomotor tone seen in hyporeninemic hypoaldosteronism.

Mechanism of action of vasoconstrictor responses to atriopeptin II in conscious SHR.

Previous studies have demonstrated that infusion of synthetic atriopeptin II (AP II) lowered arterial pressure, reduced regional blood flow, and increased total peripheral and regional vascular resistances in conscious spontaneously hypertensive rats (SHR). This study was designed to examine the mechanism(s) involved in regional vasoconstrictor responses to AP II. In these experiments, hemodynamic actions of AP II were examined in control, 6-hydroxydopamine-treated (chemically sympathectomized), and renal-denervated groups of instrumented conscious SHR. Infusion of AP II (1 microgram X kg-1 X min-1) caused similar reductions in mean arterial pressure in control (-22 +/- 2 mmHg), chemically sympathectomized (-23 +/- 2 mmHg), and renal-denervated (-23 +/- 3 mmHg) SHR. In control SHR, AP II infusion reduced renal (-20 +/- 3%), mesenteric (-26 +/- 2%), and hindquarters (-18 +/- 10%) blood flow and increased regional vascular resistance in all three beds. Chemical sympathectomy prevented the fall in renal blood flow (RBF) and significantly abolished the regional vasoconstrictor responses to AP II infusion. In unilateral renal-denervated groups of SHR, AP II reduced renal vascular resistance (RVR) -11 +/- 3% but failed to alter RBF (-3 +/- 1%) in denervated kidneys. In contrast, RVR increased (20 +/- 7%) and RBF was significantly reduced (-29 +/- 3%) in contralateral-innervated kidneys. This study demonstrated that chemical or surgical destruction of renal sympathetic nerves abolished AP II-induced increases in RVR. These data further indicate that in conscious SHR the regional vasoconstrictor responses to AP II infusion appear to be mediated by increases in sympathetic tone rather than through direct vascular actions of AP II.

Effect of cyclosporine administration on renal hemodynamics in conscious rats

The effect of acute and chronic administration of cyclosporine on systemic and renal hemodynamics was studied in conscious rats. Infusion of cyclosporine in a dose of 20 mg/kg (Cy 20) resulted in a significant fall in renal blood flow (RBF) (3.4 vs. 6.5 ml/min/g, P less than 0.05) and a rise in renal vascular resistance (RVR) (36.9 vs. 20.6 mm Hg/ml/min/g, P less than 0.05). Infusion of cyclosporine at a dose of 10 mg/kg (Cy 10) did not result in a significant change in RBF or RVR. Both doses of cyclosporine resulted in stimulation of plasma renin activity (PRA) from control values of 5.6 +/- 0.8 ng/ml/hr to 11.6 +/- 2.0 with 10 mg/kg and 26.7 +/- 5.6 with 20 mg/kg. Urinary 6-keto-PGF1 alpha excretion increased from control values of 14.0 +/- 2.0 ng/6 hr to 22.7 +/- 2.2 with 10 mg/kg and 25.0 +/- 2.0 with 20 mg/kg. Similar effects on RBF, RVR, PRA, and 6-keto-PGF1 alpha excretion were seen after chronic administration of cyclosporine (20 mg/kg i.p. for 7 days). Pretreatment of animals with captopril did not prevent the fall in RBF after cyclosporine, suggesting that the vasoconstriction was not mediated by angiotensin II. Animals treated with meclofenamate demonstrated reduction in RBF with 10 mg/kg cyclosporine (4.3 vs. 7.0 ml/min/g, P less than 0.05), suggesting that prostaglandins protect against the vasoconstrictor effect of cyclosporine. Administration of phenoxybenzamine after cyclosporine improved RBF (5.0 vs. 3.4 ml/min/g) and restored RVR to normal. Similarly, renal denervation dramatically reduced the fall in RBF after cyclosporine (innervated right kidney 3.6 vs. denervated left kidney 6.0 ml/min/g, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Nadolol in essential hypertension: effect on ambulatory blood pressure, renal haemodynamics and cardiac function.

Chronic administration of nadolol has been reported to reduce blood pressure either without or with a concomitant fall of renal blood flow. We therefore studied the effects of nadolol 80 mg once daily on ambulatory blood pressure, renal and systemic haemodynamics in patients with mild to moderate essential hypertension. Ten patients took part in this randomized, double-blind, placebo-controlled, crossover study, each phase of which lasted 4 weeks. Nadolol significantly reduced ambulatory blood pressure and heart rate, but had no effect on blood pressure variability. Cardiac output was significantly reduced by nadolol and total peripheral resistance increased but without reaching statistical significance. Despite the fall in blood pressure and cardiac output, renal blood flow and glomerular filtration rate remained unchanged. The fraction of cardiac output reaching the kidneys rose significantly and renal vascular resistance was significantly reduced. Body weight, urinary sodium excretion and urine flow rate remained unchanged. We conclude that nadolol 80 mg once daily lowers ambulatory blood pressure in patients with mild to moderate hypertension without impairment of renal blood flow, indicating a redistribution of cardiac output to the kidneys. The mechanism of the renal vasodilator effect of nadolol remains to be determined.

The subtype of alpha-adrenoceptor involved in the neural control of renal tubular sodium reabsorption in the rabbit.

A study was undertaken in pentobarbitone anaesthetized rabbits, undergoing a saline diuresis, to determine the subtype of alpha-adrenoceptor mediating renal tubular sodium reabsorption. Stimulation of the renal nerves at low rates, to cause an 11% fall in renal blood flow, did not change glomerular filtration rate but significantly reduced urine flow rate, and absolute and fractional sodium excretions by approximately 40%. These responses were reproducible in different groups of animals and with time. Renal nerve stimulation during an intra-renal arterial infusion of prazosin, to block alpha 1-adrenoceptors, had no effect on the renal haemodynamic response but completely abolished the reductions in urine flow rate, and absolute and fractional sodium excretion. During intra-renal arterial infusion of yohimbine, to block renal alpha 2-adrenoceptors, stimulation of the renal nerves to cause similar renal haemodynamic changes resulted in significantly larger reductions in urine flow rate, and absolute and fractional sodium excretion of about 52-58%. These results indicate that in the rabbit alpha 1-adrenoceptors are present on the renal tubules, which mediate the increase in sodium reabsorption caused by renal nerve stimulation. They further suggest the presence of presynaptic alpha 2-adrenoceptors on those nerves innervating the renal tubules.

Resting and exercise renal blood flows in immature ovine aortic coarctation. Impact of gradient relief.

The primary purpose of this study was to determine whether a neonatally induced thoracic aortic coarctation reduces renal blood flow during physiological stress (treadmill exercise), and whether relief of the gradient returned renal blood flow during exercise to normal. Two ancillary questions were also addressed: dose a coarctation after the responses of enteric and other visceral vascular beds to treadmill exercise? Eight newborn lambs that underwent sham thoracotomy with placement of left atrial lines served as controls; in seven lambs we also created a recently described form of dilatable juxtaductal coarctation. This preparation is unique in that, like human coarctation, the obstruction does not get worse as the animal grows. Rest and exercise vascular pressures and regional blood flows were determined 2-2 1/2 months after surgery. Coarctations were relieved with balloon dilation angioplasty catheters, inserted percutaneously. Postdilation rest and exercise hemodynamic studies were performed, at the same level of exercise, 24 hours after dilation. Renal blood flow did not change with exercise in the control animals. In lambs with coarctation, renal blood flow fell (-22%, P less than 0.01) during exercise. Unexpectedly, an exercise-induced fall in renal blood flow (-22%, P less than 0.001) persisted even after effective relief of the coarctation (descending aortic blood pressure fell 25% with exercise predilation, but remained unchanged with exercise postdilation). Blood flow to the terminal ileum and cecum followed a qualitatively similar pattern to that of renal blood flow in control, predilation, and postdilation lambs, and this pattern was distinct from that of other enteric and visceral organ flows. These results demonstrate an expected abnormality in the regulation of exercise renal blood flow in lambs with coarctation of the aorta; however, the persistence of this abnormality after effective gradient relief does not support the previously advanced theory that postcoarctation hypertension is largely nonrenal in origin. The apparent similarity between ileocecal and renal blood flow control under these circumstances may provide a clue to the known predilection of the terminal ileum to suffer ischemic injury.

Dose-dependent effects of meclofenamate on peripheral vasculature of conscious rabbits.

1. Changes in systemic haemodynamics and organ blood flow were measured in conscious rabbits after various doses of intravenous sodium meclofenamate, an inhibitor of prostaglandin cyclo-oxygenase. 2. Meclofenamate had no effect on arterial pressure or cardiac output but caused a dose-dependent fall in renal blood flow. 3. Meclofenamate also reduced adrenal perfusion but, in contrast, caused a dose-dependent increase in blood flow to the brain, bronchial and hepatic circulation and to the testis. No effect was demonstrated on other organs studied. 4. The effect on the cerebral circulation was observed at the lowest dose of meclofenamate (0.75 mg/kg). Higher total doses were necessary for an effect on the renal and bronchial (3 mg/kg) and testicular and hepatic arteries (6 mg/kg). 5. The results suggest a variety of local vasomotor influences of renal and non-renal prostaglandins in conscious rabbits.

Dissociation of glomerular filtration and renal blood flow in HgCl2-induced acute renal failure

This study evaluates the role of early renal vasoconstriction in the pathogenesis of mercuric chloride (HgCl2)-induced acute renal failure (ARF) in the dog. Within 3 hr after mercury, glomerular filtration rate (GFR), from 45 +/- 4 25 +/- 2 ml/min, and renal blood flow (RBF), from 268 +/- 22 to 161 +/- 19 ml/min, decreased simultaneously. A rise in diuresis and urinary solute excretion occurred. Morphological and functional studies excluded a major role for tubular leakage or obstruction. An attempt was made to prevent the early renal vasoconstriction, by the administration of Haemaccel, a plasma volume expander, alone or in combination with phentolamine. In both settings the fall in RBF after mercury was prevented. Haemaccel volume expansion alone provoked a significant rise in GFR before HgCl2, but the GFR fell by 29% 3 hr after HgCl2. The Haemaccel/phentolamine combination had no influence on pre-mercury GFR values. In this group, a decrease of GFR by 44% was noted 3 hr after mercury. In conclusion, changes in GFR and renal hemodynamics can be dissociated in the early phase of nephrotoxic ARF. The fall in GFR can be attributed either to a decrease in glomerular ultrafiltration capacity and/or changes in glomerular afferent and efferent resistances, leading to a decrease in glomerular hydrostatic pressure.

Enhanced cardiac efficiency with dobutamine after global ischemia

Dopamine and dobutamine are used in low output states following cardiopulmonary bypass but the consequences of increased inotropic activity on myocardium recovering from ischemia is unknown. Dogs on cardiopulmonary bypass were subjected to 20 min of normothermic global ischemia followed by 20 min of reperfusion. Dopamine or dobutamine (both at 10 μg/kg/min) or normal saline infusion was begun and 10 min later the dogs weaned from cardiopulmonary bypass while the infusions continued. Serial measurements were made of regional myocardial and systemic blood flow (15 μm radiolabeled spheres), myocardial oxygen consumption, creatine phosphate, and ATP levels. On bypass mean aortic pressure was decreased and heart rate, oxygen consumption, and left ventricular blood flow were increased by both catecholamine infusions ( P < 0.01), but neither drug lowered ATP or creatine phosphate levels. Renal blood flow was decreased in dobutamine-treated dogs ( P < 0.01). Off bypass, heart rate and mean aortic pressure were similar in all groups. While both drugs increased left ventricular blood flow to a similar extent ( P < 0.01), dopamine treatment raised cardiac output by only 30% ( P < 0.05) and dobutamine treatment increased cardiac output by 85% ( P < 0.01). In addition, myocardial oxygen consumption was increased in dopamine-treated dogs ( P < 0.05) while values in dobutamine animals were similar to controls. Therefore, dobutamine seems advantageous to dopamine following bypass because it increases cardiac output (by increasing stroke volume) but does not increase myocardial oxygen consumption. Both drugs are potentially detrimental on bypass because they greatly increase heart rate and oxygen consumption and, in addition, dobutamine causes an unexplained fall in renal blood flow.

Influence of the renin-angiotensin system in the renal haemodynamic responses to modest renal nerve stimulation in the rat.

The renal nerves of the left kidney of sodium-replete anaesthetized rats were stimulated for 30-min periods at 2-3 Hz (15 V, 0.2 ms). Renal blood flow was reduced by 22% and glomerular filtration rate by 14% which resulted in a rise in filtration fraction of 12%. Circulating plasma renin activity was increased by 30% during such nerve stimulation. In rats treated for 3-4 weeks with deoxycorticosterone acetate (DOCA) and saline (150 mM-NaCl) basal values of arterial blood pressure, renal blood flow, glomerular filtration rate and filtration fraction were not significantly different from those observed in sodium-replete rats. However, plasma renin activity was lower, being approximately one-third of that observed in sodium-replete animals. Stimulation of the renal nerves in rats treated with DOCA and saline resulted in a fall in renal blood flow of 32% and a much larger fall in glomerular filtration rate of 33% which resulted in no change in filtration fraction. Plasma renin activity was not changed by renal nerve stimulation in the animals treated with DOCA and saline. It is suggested that these renal responses provide evidence in the rat for a role of locally generated angiotensin II in regulating glomerular filtration rate during electrical activation of the renal nerves by causing preferential vasoconstriction of the efferent arteriole.