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.     

Differentiation of cutaneous and intestinal blood flow during hypothalamic heating and cooling in anesthetized dogs

Summary Blood flow in arteries supplying cutaneous and intestinal vascular regions were simultaneously measured with an electromagnetic flowmeter in anesthetized dogs, paralyzed with succinyl choline. The hypothalamic preoptic region was selectively heated and cooled by means of a stereotaxically inserted, water perfused thermode.Skin blood flow increased during hypothalamic heating and was reduced during hypothalamic cooling. Conversely, intestinal blood flow decreased during heating and increased during cooling. Arterial pressure was not influenced by hypothalamic cooling and decreased slightly during heating.The changes of blood flow distribution observed in the experiments are in keeping with the results obtained during selective spinal cord heating and cooling. It is assumed that antagonistic changes of blood flow in the cutaneous and intestinal vascular beds represent typical thermoregulatory responses of systemic circulation induced by regionally antagonistic changes of vasomotor activity.     

Influence of pulsatile perfusion upon renin release from the isolated perfused rat kidney

It is well established that renin release from the juxtaglomerular epithelioid cells in the media of the afferent arteriole strongly depends on the mean renal perfusion pressure, whereas a possible influence of the pulsation of blood pressure on renin release has only occasionally been investigated, and the results are contradictory. Such an influence on renin release cannot be excluded because pulsation is known to modulate arterial baroreceptors and vascular tone in some resistance vessels. In the isolated perfused rat kidney, we found a pulsation amplitude-dependent inhibition of renin release that could be blocked either by vasodilatation or by calcium channel blockade. The inhibition occurred at perfusion pressures between 85 and 125 mm Hg. The underlying pulsation pressure-sensitive mechanism has to be ascribed integrating properties, because a constantflow pressure rise to the “systolic” value of pulsatile perfusion resulted in virtually the same inhibition of renin release. Moreover, a reduced urine flow during pulsatile perfusion provides evidence for preglomerular constriction under these conditions. It is concluded that, besides pathological changes of renal perfusion pressure, variations of the pulse amplitudes, e.g. resulting from renal artery stenosis or atherosclerosis, may also influence renin release and contribute to renovascular hypertension.     

The influence of aortic baroreceptors on venous tone in the perfused hind limb of the dog.

1. The aortic arch and both carotid sinuses were vascularly isolated and perfused. A hind limb was vascularly isolated and blood was pumped at constant flows into the femoral artery and the central end of a superficial metatarsal vein. 2. Large increases in aortic arch pressure resulted in decreases in arterial blood pressure, heart rate and femoral arterial perfusion pressure. The average response of the vein was a decrease of 11% in the pressure gradient between the perfused vein and the femoral vein. Similar responses were obtained when carotid sinus pressure was increased. 3. Crushing or cooling the lumbar sympathetic trunk caused responsed similar to those induced by increasing baroreceptor perfusion pressure. Stimulation at 1 HZ resulted in venous responses four times as great as the average reflex response, whereas frequencies of 2-5 Hz were required to produce changes in arterial resistance as great as those induced reflexly. 4. These experiments indicate, that although the large superficial veins of the dog's hind limb participate in the baroreceptor reflexes, the activities in the nerves supplying arterioles and veins must have been different.     

Lingual blood flow and its hypothalamic control in the dog during panting

1. The effects of increased ambient temperature (Ta) on blood-flow and -temperatures of the tongue were studied in the unanaesthetized dog. At Ta of 20 degrees C and a relative humidity (rh) of 30% the mean lingual blood flow was 11 ml-min-1 (0.15 ml-g-1-min-1) and the temperature difference between the lingual artery and vein (deltaTLAV) was 1.0 degrees C. Accordingly, a heat loss of 48.6 J-min-1 was calculated even for the dog breathing with the mouth closed. When Ta was elevated to 38 degrees C at constant rh, panting ensued. In parallel fashion lingual blood flow increased to 60.4 ml-min-1 (0.81 ml-g-1-min-1) in mean and to 74.7 ml-min-1 (0.99 ml-g-1-min-1) at peak rate of thermal tachypnoea (272 breaths-min-1). This flow increase resulted from a decrease in the local vascular resistance since the driving systemic pressure remained constant. It was accompanied by an increase in TLAV to 1.5 degrees C equivalent to a heat loss of 400.7J-min-1 in mean and 496.2J-min-1 at maximum respiratory rate. 2. The preoptic/anterior hypothalamic (PO/AH) region was heated with a water perfused thermode in urethane anaesthetized dogs at constant body temperature in order to study the relationship in time between the increase in lingual blood flow and the onset of thermal panting. Lingual blood flow was found to be 20 ml-min-1 at a respiratory rate of 60 breaths/min. During hypothalamic heating both respiratory rate and lingual blood flow increased markedly. At maximum respiratory rates (244 breaths-min-1) lingual blood flow reached a level of 60 ml-min-1. When perfusion of the thermode was stopped, both respiratory rate and lingual blood flow synchronously returned to control values within 5 min. Similar changes did not occur in dogs in which a ventilatory response failed to be elicited during hypothalamic heating. 3. The results suggest that the tongue contributes to the evaporative heat loss mechanism and they confirm the concept that panting, associated with increased lingual blood flow, is induced by a common autonomic outflow pattern which is mediated by the central mechanism controlling thermal homeostasis.     

Parabrachial pons mediates hypothalamically induced renal vasoconstriction

The role of the parabrachial region of the dorsal rostral pons (PB) in mediating control of renal blood flow and of systemic arterial blood pressure was investigated in nine cats anesthetized with chloralose-urethan. Electrical stimulation through electrodes placed stereotaxically in lateral and medial positions in the hypothalamus (LH and MH) in PB and in ventrolateral reticular formation (VLRF) of each cat elicited pronounced systemic arterial pressor responses and renal vasoconstrictions. Stimulation parameters were adjusted so that renal flow responses elicited from each site were equal. Following a unilateral lesion in the PB, responses of renal vasoconstriction induced by hypothalamic stimulation were attenuated, but responses of arterial pressure were not altered. Stimulation of the VLRF, posterior to the lesion, consistently produced undiminished systemic pressor responses and renal vasoconstriction throughout the durations of the experiments excluding decay of renal vascular responsiveness. Thus, the data suggest that pathways mediating renal vasoconstriction in response to hypothalamic stimulation was discrete and pass through the parabrachial region, whereas pathways mediating systemic vasoconstriction in response to hypothalamic stimulation are distinct or less compact.     

The vasomotor component of the carotid sinus baroreceptor reflex in the cat during stimulation of the hypothalamic defence area

1. The effect of moderate intensities of stimulation of the hypothalamic defence area on the baroreceptor reflex has been investigated in the cat by comparing the responses of arterial blood pressure and perfusion pressure of the isolated hind-limb muscle bed perfused at constant volume inflow, when the isolated carotid sinus was subjected to a series of non-pulsatile pressures with and without simultaneous hypothalamic stimulation.2. In the absence of hypothalamic stimulation the characteristic sigmoid curves relating sinus pressure to blood pressure or muscle perfusion pressure were obtained.3. With simultaneous stimulation of the hypothalamus a similar sigmoid relationship was found. There was no evidence of any reduction in the over-all power or maximum sensitivity of the baroreceptor reflex.4. However, in those cats which had been atropinized to abolish the cholinergically mediated muscle vasodilatation, the curves obtained during hypothalamic stimulation were displaced in such a manner as to suggest that, while baroreceptor modulation of vasoconstrictor tone continued during defence area stimulation, the blood pressure regulating mechanism had been ;reset' so that, within the physiological range of sinus pressures, any given level of sinus pressure was associated with a greater vasoconstrictor tone.5. In non-atropinized cats there was little displacement of the curves relating sinus pressure to blood pressure, while the curves relating sinus pressure to muscle perfusion pressure were displaced in the opposite direction so that over-all muscle vascular resistance was less than normal at each level of sinus pressure.     

Reflex responses from the main pulmonary artery and bifurcation in anaesthetised dogs

This study was undertaken to determine the reflex cardiovascular and respiratory responses to discrete stimulation of pulmonary arterial baroreceptors using a preparation in which secondary modulation of responses from other reflexes was prevented. Dogs were anaesthetised with -chloralose, artificially ventilated, the chests widely opened and a cardiopulmonary bypass established. The main pulmonary arterial trunk, bifurcation and extrapulmonary arteries as far as the first lobar arteries on each side were vascularly isolated and perfused through the left pulmonary artery and drained via the right artery through a Starling resistance which controlled pulmonary arterial pressure. Pressures distending systemic baroreceptors and reflexogenic regions in the heart were controlled. Reflex vascular responses were assessed from changes in perfusion pressures to a vascularly isolated hind limb and to the remainder of the subdiaphragmatic systemic circulation, both of which were perfused at constant flows. Respiratory responses were assessed from recordings of efferent phrenic nerve activity. Increases in pulmonary arterial pressure consistently evoked increases in both perfusion pressures and in phrenic nerve activity. Both vascular and respiratory responses were obtained when pulmonary arterial pressure was increased to above about 30 mmHg. Responses increased at higher levels of pulmonary arterial pressures. In 13 dogs increases in pulmonary arterial pressure to 45 mmHg increased systemic perfusion pressure by 24 +/- 7 mmHg (mean +/- S.E.M.) from 162 +/- 11 mmHg. Setting carotid sinus pressure at different levels did not influence the vascular response to changes in pulmonary arterial pressure. The presence of a negative intrathoracic pressure of -20 mmHg resulted in larger vascular responses being obtained at lower levels of pulmonary arterial pressure. This indicates that the reflex may be more effective in the intact closed-chest animal. These results demonstrate that stimulation of pulmonary arterial baroreceptors evokes a pressor reflex and augments respiratory drive. This reflex is likely to be elicited in circumstances where pulmonary arterial pressure increases and the negative excursions of intrathoracic pressure become greater. They are likely, therefore, to be involved in the cardio-respiratory response to exercise as well as in pathological states such as pulmonary hypertension or restrictive or obstructive lung disease.     

Metabolism, sperm and fluid production of the isolated perfused testis of the sheep and goat

1. A total of nineteen ram and three goat testes have been perfused in isolation at 34-35 degrees C for 3(1/2)-9 hr with heparinized blood and an added 5-HT antagonist (bromolysergic acid diethylamide) and their function compared with that of the normal ram testes in vivo.2. The metabolism of the perfused testes and the testes in vivo was similar but blood flow through the perfused testes was two to three times normal.3. Vasoconstriction was produced by adrenaline and noradrenaline (10-20 mug I.A.) and by electrical stimulation of nerves in the spermatic cord or of the lumbar sympathetic chain; these responses were abolished or reduced by phenoxybenzamine.4. Flow of fluid from the rete testis continued only if ischaemia was reduced to a minimum and glucose concentration in the blood perfusing the testis was kept above about 25 mg/100 ml.; the fluid secreted during perfusion was of normal composition.5. The perfused testis showed no evidence of autoregulation and the flow of fluid was not affected by changes in perfusion pressure.6. When the temperature of three testes was raised to 40 degrees C for 2 hr, metabolism increased but blood flow was unaltered; the flow of fluid and the concentration of spermatozoa decreased during heating.7. The testes perfused at normal scrotal temperatures (34-35 degrees C) were histologically normal but some abnormalities were observed in the heated testes.     

Renal P2 receptors and hypertension

The regulation of extracellular fluid volume is a key component of blood pressure homeostasis. Long‐term blood pressure is stabilized by the acute pressure natriuresis response by which changes in renal perfusion pressure evoke corresponding changes in renal sodium excretion. A wealth of experimental evidence suggests that a defect in the pressure natriuresis response contributes to the development and maintenance of hypertension. The mechanisms underlying the relationship between renal perfusion pressure and sodium excretion are incompletely understood. Increased blood flow through the vasa recta increases renal interstitial hydrostatic pressure, thereby reducing the driving force for transepithelial sodium reabsorption. Paracrine signalling also contributes to the overall natriuretic response by inhibiting tubular sodium reabsorption in several nephron segments. In this brief review, we discuss the role of purinergic signalling in the renal control of blood pressure. ATP is released from renal tubule and vascular cells in response to increased flow and can activate P2 receptor subtypes expressed in both epithelial and vascular endothelial/smooth muscle cells. In concert, these effects integrate the vascular and tubular responses to increased perfusion pressure and targeting P2 receptors, particularly P2X7, may prove beneficial for treatment of hypertension.     

Renal and haemodynamic effects of nitric oxide blockade in a Wistar assay rat during high pressure cross-circulation of an isolated denervated kidney

Blockade of NO synthesis with N-ω-nitro-L-arginine (L-NNA) inhibits the vasodepressor response seen in intact Wistar assay rats in which isolated kidneys perfused via an extracorporeal circuit are perfused at high pressure. This study explores the renal and haemodynamic changes associated with this inhibition. Isolated kidneys (IK) were perfused at high pressure (175 mmHg) by a pump in series with intact Wistar assay rats in which blood pressure (BP), haemodynamics and renal function were studied. Nitric oxide (NO) synthesis was blocked by L-NNA (2.5 mg kg^-1) in 13 experiments (175NO) while 14 control experiments (175C) were performed. IK was perfused at 90 mmHg in seven experiments (90C). The BP drop in the 175C assay rat was blocked by L-NNA in 175NO (P < 0.01). However, when the blockade was reversed with L-arginine infusion (20 mg kg ^J min“¹) BP declined also in 175NO. Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) fell dramatically after L-NNA in both the assay rat and in IK despite a high perfusion pressure. The marked increase in filtration fraction (FF) after L-NNA suggests a dominating postglomerular vasoconstriction. The natriuretic response in IK to 175 mmHg was also markedly blunted by L-NNA. We conclude that NO blockade inhibits the renomedullary depressor mechanism probably by restricting renal blood flow, and also blunts the pressure induced natriuretic response as a result of a reduced sodium filtration. Finally, the autoregulation of whole kidney blood flow seems to be more efficient although set at a higher level of vasoconstriction.     

Renal blood flow autoregulation in developing swine

Pressure-flow relationships (P/F) in the renal circulation were determined in 62 swine, aged 1 day-2 mo, anesthetized with pentobarbital sodium. Aortic and inferior vena caval pressures and renal and femoral arterial flows were recorded. Blood gas composition and pH and body temperature were monitored. The P/F was first determined while perfusion pressure was decreased for 2 min at each pressure by suprarenal aortic occlusion. The left renal artery in 38 of these animals was then cannulated for in situ perfusion of the kidney with blood withdrawn from a carotid artery by a Masterflex pump. The P/F was subsequently determined by changing pump flow for 2 min at each flow while recording perfusion pressure. Records were analyzed for transient and steady-state effects. Readjustments in renal vascular resistance (RVR) were apparent within 5 s after changing pressure or flow. The RVR stabilized at a new level within 2 min. Graphs of steady-state data delineated an autoregulatory range in the P/F for animals as young as 2 wk of age. We conclude that renal blood flow autoregulation in this mammal is negligible at birth and develops progressively during the first postnatal month.     

Diaphragmatic blood flow at various levels of ventilation in the rabbit.

Diaphragmatic and renal blood flow were measured with Ytterbium-169 and Scandium 46 labelled 15 micron microspheres in sodium pentobarbitone anesthetized rabbits. The first measurement was performed during spontaneous breathing of air and the second measurement after 15 min of breathing 2-6% carbon dioxide in oxygen. The lung ventilation as well as the diaphragmatic blood flow increased significantly during breathing of the carbon dioxide-oxygen mixture. Arterial blood pressure and renal blood flow were not significantly altered by the induced hyperventilation. No significant correlation was found between the magnitude of lung ventilation and diaphragmatic blood flow. The results of the present study indicate that consecutive measurements of diaphragmatic blood flow with radioactive microspheres at various levels of breathing effort is an appropriate method for further exploration of the relationship between diaphragmatic perfusion and working performance.     

Effect of hypoxia on vascular responses to the carotid baroreflex.

The effect of systemic hypoxia on the vascular responses to the carotid baroreflex was studied in anesthetized, vagotomized, artificially ventilated dogs. One hindlimb, kidney, gracilis muscle, and paw were perfused at constant flow, and neurograms were obtained from renal sympathetic fibers. Bilateral carotid occlusions were performed while the animal was breathing a mixture of air and O2 (mean arterial PO2 = 106 mmHg) and again during ventilation with 10% O2 (PO2 = 40 mmHg). With occlusion, the average increase in mean aortic pressure was 36 mmHg greater during hypoxia than during normoxia and the increase in renal perfusion pressure was 87 mmHg greater; the increase in hindlimb perfusion pressure was identical in both situations. Hypoxia did not change the reflex response of the paw to carotid occlusion and increased that of the muscle vessels by only 10%; the increase in renal sympathetic activity averaged 56 plus or minus 10% more with hypoxia than with normoxia. When the carotid chemoreceptors were destroyed, the greater increase in aortic and renal pressure response to carotid occlusion during hypoxia as compared to normoxia was abolished. Thus systemic hypoxia markedly potentiates the reflex renal constriction caused by the baroreflex, and this effect is due to the carotid chemoreceptor afferent input.     

Pump perfusion causes vasodilation by activation of platelets

Use of a pump in extracorporeal circuits depresses autoregulation and vascular tone. To study whether platelets are involved, we perfused rat hindlegs by means of an extracorporeal shunt between carotid and femoral artery. Autoperfusion could instantaneously be replaced by pump perfusion. To avoid interference by effects caused by blood-material contact, the circuit was coated with albumin. Spontaneous flow did not elicit platelet aggregation as recorded continuously with a photometric device inserted into the tubing, nor did it affect femoral vascular resistance. However, pump perfusion immediately evoked strong platelet aggregation that stabilized at a lower level after 2-3 minutes. Femoral resistance rose slightly during the first 2 minutes, but thereafter fell to 63% of control and stayed at approximately 70% for the next 2 hours. Pump induced platelet aggregation and fall in vascular resistance could be prevented with aurintricarboxylic acid, which specifically inhibits shear induced platelet aggregation. We conclude that pump perfusion with blood in coated systems elicits shear-induced platelet aggregation that, in turn, leads to vasodilation in the perfused vascular bed. These effects can be prevented by blocking the binding of von Willebrand factor to the platelet glycoprotein Ib receptors.     

The site of action of nerves in the pulmonary vascular bed in the dog

1. The effects of stimulation of the thoracic vagosympathetic nerve or upper thoracic sympathetic chain on the pulmonary vascular resistance have been studied in atropinized, isolated, ventilated lung lobes under various conditions of pulmonary circulation perfusion. Throughout the nerve-stimulation tests bronchial circulation perfusion was maintained or temporarily interrupted.2. The pulmonary vascular resistance increase evoked by nerve stimulation (a) occurred in the absence of tidal air changes; (b) did not consistently differ during predominantly ;sluice' and ;non-sluice' conditions of pulmonary circulation perfusion; (c) was approximately one and a half times greater during constant pressure than during constant volume inflow perfusion of the pulmonary circulation; and (d) was greater during reverse than during forward perfusion.3. In lung lobes perfused in either direction at constant volume inflow nerve stimulation produced an increase in inflow pressure and a diminution in total lung blood volume reflected by a temporary increase in blood outflow.4. In lung lobes in which neither the pulmonary nor the bronchial circulations were perfused and the capillaries were completely blocked by high intratracheal pressures, thus isolating the pulmonary arterial system from the venous system, nerve stimulation produced a diminution in the blood volume of both systems.5. Nerve stimulation produced a rise in bronchial arterial pressure in the absence of pulmonary circulation perfusion.6. Further evidence is adduced that pulmonary vasomotor nerve responses do not depend upon the transfer of transmitter substances from the bronchial to the pulmonary circulation.7. The possible significance of these observations in relation to the site of action of pulmonary vasomotor nerves is discussed.     

Acute intracranial hypertension and basilar artery blood flow velocity recorded by transcranial Doppler sonography: an experimental study in rabbits.

The relationship between intracranial hypertension and basilar artery blood flow is not well known, and it is not yet definite that the reduction of cerebral flow depends on cerebral perfusion pressure rather than microvessel compression. The purpose of the study described here was to investigate the effect of acute intracranial pressure on the basilar flow velocity, the cerebral perfusion pressure, and the systemic arterial pressure. The basilar Doppler signal was recorded continuously in 24 New Zealand rabbits by transcranial pulsed Doppler method. The acute intracranial hypertension was induced by the progressive raising, in steps of 5 mmHg, of a saline infusion bottle connected to an epidural sensor. The intracranial hypertension induced a decrease in diastolic and mean flow velocities in the basilar artery, and an increase in the resistance index. Cerebral perfusion pressure was significantly correlated with flow parameters. The basilar diastolic flow began to decrease significantly from a 35-40 mmHg intracranial pressure and for a 37 mmHg + 20 SD cerebral perfusion pressure, without significant variation of arterial pressure. Diastolic flow dropped to zero for a 53 mmHg intracranial pressure and a 30 mmHg + 15 SD cerebral perfusion pressure. These results show that high intracranial pressure values are necessary for significantly reducing basilar artery blood flow. This effect, and the increase of circulatory cerebral resistance, occurred before significant changes in systemic arterial pressure.     

Resetting of the pressure range for blood flow autoregulation in the rat kidney

Both a myogenic response and the tubuloglomerular feedback control mechanism seem to be involved in autoregulation of glomerular filtration rate (GFR) and renal blood flow (RBF). Earlier experiments have shown that clamping of renal arterial perfusion pressure, below the autoregulatory range, reduces single-nephron GFR, and that this low value is maintained during the first 10-15 min after release of the clamp. It was also found that the tubuloglomerular feedback mechanism in the early declamp phase was strongly activated to reduce GFR. These findings can not be easily understood with the current knowledge of autoregulation, but would suggest a resetting of RBF and GFR autoregulation to a new level. To test this, left renal arterial perfusion pressure was reduced from 100 to 60 mmHg during 20 min with and without angiotensin converting enzyme inhibition (0.5 mg i.v. enalapril). Renal blood flow was measured with laser-Doppler flowmetry. When arterial perfusion pressure was reduced from 100 to 60 mmHg for 20 min, RBF was reduced to 77% of control and remained at this low level during the first minutes of declamp. In this situation there was an autoregulation to a new level. Renal blood flow was then slowly normalized (16.1 min). In the enalapril-treated animals RBF was only reduced to 85% during the 20 min of clamping and returned immediately to the control level at declamp. Thus, these experiments demonstrate that if renal blood flow is decreased by reducing the perfusion pressure below the normal autoregulatory range the pressure range for blood flow autoregulation resets to a lower level and that this change is mediated via the renin-angiotensin system.     

Effects of variations in renal hemodynamics on the time course of renin secretion rate

The effects of variations in renal hemodynamics on the time course of renin secretion were studied in dogs anesthetized with pentobarbital-chloralose. Hemodynamic changes were induced either locally in kidneys perfused in situ via an extracorporeal circuit (with or without a pump system) or systemically by hemorrhage or nitroprusside infusion. In the autoperfused kidney the reduction of renal perfusion pressure to approximately one-half of the arterial pressure by inflow occlusion caused an increase in renal conductance (renal vasodilation) and an increase in renin secretion rate (RSR). In the pump-perfused kidney, a step increase in renal blood flow (RBF) caused renal vasoconstriction and a decrease in RSR; a step decrease in RBF caused renal vasodilation and an increase in RSR. Following step changes in RBF, the time constant of the alterations of renal conductance was 56.5 s, and the time constant of the RSR responses was 80.1 s. The total time required to reach a steady state for RSR lagged behind that for renal conductance by approximately 5 min. These differences reflect the time needed for the kidney to release renin in response to changes in renal vascular caliber. The results suggest that renin release occurs in response to the autoregulatory dilation of the renal arterioles. When systemic hypotension was induced by nitroprusside infusion, RSR also increased together with the renal conductance. Following hemorrhage, however, RSR increased despite a decrease in renal conductance, reflecting the role of neurohumoral factors in causing renin release in this case. The comparison of renin secretion following different types of hemodynamic alterations serves to elucidate the mechanisms of renin secretion.     

Relationship between perfusion pressure and renin release in the isolated rat kidney

Summary Isolated rat kidneys were perfused with either a modified Krebs-Henseleit solution containing a gelatine preparation (Haemaccel, 35 g/l) or with a suspension of washed bovine red blood cells (RBC). When perfusion pressure (PP) was varied repeatedly in the range between 30 and 210 mm Hg autoregulation of renal plasma flow (RPF) was almost complete in RBC perfused kindneys. Changes of PP by steps of 20 mm Hg at intervals of 5 min resulted in an incomplete autoregulation of RPF and glomerular filtration rate (GFR). Renin release (RR) was inversely related to PP in the range between 50 and 150 mm Hg, while perfusion at a pressure below or above that range had no further effect on RR. The most marked increase in RR was obtained, when PP was reduced from 90 to 70 mm Hg. After reduction of PP, an increase in RR was measurable within 1 min, and a maximum was reached after 5 min. In kidneys perfused with a cell-free medium at a PP of 45 mm Hg for up to 30 min, RR remained elevated for the entire period of pressure reduction. Injection of microspheres into the renal artery resulted in a prompt decrease of RPF, GFR and urinary sodium excretion, but the values returned towards control levels within 15 min; RR increased only transiently after a short initial fall.