Local vascular responses to elevation of an organ above the heart

Elevation of an organ above the heart reduces the arterial and venous hydrostatic pressures in proportion to the height of elevation. Intact autoregulation protects organs, such as the brain and skeletal muscle, from significant alterations in blood flow and hydrostatic capillary pressure due to the decrease in arterial inflow pressure during such a manoeuvre. However, the consequences of the decreased hydrostatic pressure on the venous side are far from clarified. The present study analyses the local haemodynamic effects of the decrease in arterial and venous hydrostatic pressures that occur during vertical elevation of an organ above the heart at atmospheric and raised tissue pressures (0, 10 and 30 mmHg). A sympathectomized cat skeletal muscle enclosed in a plethysmograph and perfused from the animal was used as the experimental model. The results show that elevation of the muscle above the heart at atmospheric tissue pressure created a variable vascular resistance starting at the venous outlet of the organ, and related to the difference between tissue pressure and venous outflow pressure. This resistance completely protects the organ from the hydrostatic pressure alterations on the venous side. The results also show that arterial pressure variations will exert the same haemodynamic influences on the organ as tissue pressure variations, except for the formation of the venous outflow resistance at raised tissue pressure. The application of these results to normal and injured organs, e.g. normal and injured skeletal muscle and brain, with various tissue pressures, is discussed.     

Cerebrovascular transmural pressure and autoregulation

The cerebral blood flow (CBF) response to changes in perfusion pressure mediated through decreases in arterial pressure, increases in cerebrospinal fluid (CSF) pressure and increases in jugular venous pressure was studied in anesthetized dogs. A preparation was developed in which each of the three relevant pressures could be controlled and manipulated independently of each other. In this preparation, the superior vena cava and femoral vein were cannulated and drained into a reservoir. Blood was pumped from the reservoir into the right atrium. With this system, mean arterial pressure and jugular venous pressure could be independently controlled. CSF pressure (measured in the lateral ventricle) could be manipulated via a cisternal puncture. Total and regional CBF responses to alterations in perfusion pressure were studied with the radiolabelled microsphere technique. Each hemisphere was sectioned into 13 regions: spinal cord, cerebellum, medulla, pons, midbrain, diencephalon, caudate, hippocampus, parahippocampal gyrus, and occipital, temporal, parietal and frontal lobes. Despite 30 mm Hg reductions in arterial pressure or increases in jugular venous pressure or CSF pressure, little change in CBF was observed provided the perfusion pressure (arterial pressure minus jugular venous pressure or CSF pressure depending on which pressure was of greater magnitude) was greater than the lower limit for cerebral autoregulation (approximately 60 mm Hg). However, when the perfusion pressure was reduced by any of the three different methods to levels less than 60 mm Hg (average of 48 mm Hg), a comparable reduction (25–35%) in both total and regional CBF was obtained. Thus comparable changes in the perfusion pressure gradient established by decreasing arterial pressure, increasing jugular venous pressure and increasing CSF pressure resulted in similar total and regional blood flow responses. Independent alterations of arterial and CSF pressures, and jugular venous pressure produce opposite changes in vascular transmural pressure yet result in similar CBF responses. These results show that cerebral autoregulation is a function of the perfusion pressure gradient and cannot be accounted for predominantly by myogenic mechanisms.     

Regional neurohypophyseal blood flow and its control in adult sheep

Regional neurohypophyseal and cerebral blood flows were measured by the radiolabeled microsphere technique in 30 adult sheep under light barbiturate anesthesia. Regional blood flows were determined under basal conditions. The responses of regional blood flow to alterations in arterial PCO2 and to changes in arterial blood pressure wee also determined. In addition, the relationship between regional neurohypophyseal blood flow and neurosecretory activity as judged by plasma arginine vasopressin levels was assessed. Under basal conditions median eminence blood flow averaged 461 ml.100 g-1.min-1 and did not significantly differ from neural lobe blood flow (436 ml.100 g-1.min-1). Blood flow in the neurohypophysis was about 8 times cortical and 16 times white matter blood flow in these animals. Median eminence and neural lobe blood flow proportionately increased far less than regional cortical or white matter blood flow under conditions of hypercarbia. With alteration of arterial blood pressure, regional neurohypophyseal blood flow remained constant beyond the limits of cerebral autoregulation. The neurohypophysis demonstrates a degree of blood flow homeostasis that exceeds that of any other brain area studied. Although the neurohypophysis is a diverticulum of the brain, its vascular system forms a unique functional as well as a unique anatomic unit.     

Autoregulation of cerebral blood flow during early experimental renal hypertension in the conscious dog

Using the radioactive microsphere technique, cerebral blood flow (CBF) was measured in six conscious dogs before intervention and again on the 3rd-5th days after inducing hypertension by the one-kidney Goldblatt (1-KGH) procedure. Sham-operated controls were also studied. The normal temporal variability of CBF, as well as the precision of the microsphere technique in measuring CBF were also determined in other normal dogs. A left atrial catheter was used for the microsphere injections (15 micrometer diam spheres) and an aortic catheter was used for cardiac output and blood pressure measurements. On the 3rd-5th days after 1-KGH, mean aortic pressure increased from a control value of 94 +/- 7 mmHg to 135 +/- 20 mmHg (P less than 0.005). CBF did not change significantly from the control flow of 57.1 +/- 7.9 ml/100 g per min. Calculated cerebral vascular resistance increased by 47 percent (P less than 0.025) above the control value. Hence, the early phase of experimental renal hypertension is associated with adequate autoregulation of cerebral blood flow.     

Effects of venous pressure elevation on myogenic vasoconstrictive responses to static and dynamic arterial pressures

In order to establish the nature of the stretch-evoked dynamic properties of vascular smooth muscle in arterioles, we have examined the static and dynamic effects of both arterial pulse pressure and elevated venous pressure on the resistance vessels (arteries and arterioles) in an intestinal mesenteric preparation derived from dogs. The dynamic myogenic response to stretch stimuli was directly related to both the frequency of arterial pulse pressure (1-20 c/min) and the level of venous pressure (0-45 mmHg). Under elevated venous pressure (20 mmHg), the mean arterial flow decreased with an increase in the frequency of arterial pulse pressure. The arteriolar vascular tone (namely, vascular resistance) was seen to be enhanced. We found that elevated venous pressure promotes active constriction (9-53%) of arteriolar smooth muscle (myogenic mechanism). The elevation of venous pressure also caused a rhythmic constriction (vasomotion) in the site of both vein and artery, which was completely abolished by an alpha-blocker (phentolamine). The results suggest that during venous pressure elevation a very pronounced myogenic constriction in terminal arterioles is caused by either a local neural reflex or a propagated myogenic response in the arteriolar network.     

Impaired autoregulation of cerebral blood flow in long-term type I (insulin-dependent) diabetic patients with nephropathy and retinopathy

Autoregulation of cerebral blood flow, i.e., the maintenance of cerebral blood flow within narrow limits during changes in arterial perfusion pressure, was studied in nine healthy control subjects and in 12 long-term Type I (insulin-dependent) diabetic patients with clinical microangiopathy. Cerebral blood flow was measured by the intravenous 133Xenon method. Mean arterial blood pressure was elevated approximately 30 mmHg by intravenous infusion of angiotensin amide II and lowered about 10 mmHg by intravenous infusion of trimethaphan camsylate. In the control subjects the flow/pressure curve was horizontal indicating perfect autoregulation. In the diabetic patients the flow/pressure curve showed a significant slope with a 1.9% change in CBF per 10 mmHg change in mean arterial blood pressure as compared to a slope value of -0.4% in the control subjects (P less than 0.05). Our results confirm the previous findings suggesting that autoregulation of cerebral blood flow is impaired in some long-term Type I diabetic patients with clinical microangiopathy (arteriolar hyalinosis).     

Absence of estimated glomerular pressure autoregulation during interrupted distal delivery.

Micropuncture studies in dogs have suggested that a distal tubule-to-afferent arteriole feedback system may participate in the autoregulation mechanism at the single-nephron level. To evaluate the effect of interrupted distal delivery on glomerular capillary pressure (GP) and its autoregulation, the proximal tubule was blocked with oil and maximal stop-flow pressure was measured with a micropressure servo-null system. The GP was estimated from the sum of stop-flow pressure and the plasma colloid osmotic pressure (membrane oncometer). In 18 dogs given a mild mannitol load, average +/- SD control arterial pressure was 118 +/- 16 mmHg, proximal tubule pressure was 24 +/- 5 mmHg, and estimated GP averaged 70 +/- 10 mmHg. There was a highly significant relationship between estimated GP and arterial blood pressure. Similar results were obtained in hydropenic dogs. In response to decreases in renal arterial pressure in individual dogs, stop-flow pressure and estimated GP failed to exhibit autoregulation although autoregulation of renal blood flow, GFR, and proximal tubule pressure was observed over an arterial pressure range of 150-95 mmHg. These results indicate that interruption of normal distal delivery by proximal tubule blockage interferes with the ability of the nephron to autoregulate glomerular pressure. They provide further evidence in support of the concept that a distal tubular feedback mechanism participates, at least in part, in the autoregulatory control of glomerular pressure.     

Determinants of systemic zero-flow arterial pressure

Thirteen pentobarbital-anesthetized dogs whose carotid sinuses were isolated and perfused at a constant pressure were placed on total cardiac bypass. With systemic venous pressure held at 0 mmHg (condition 1), arterial inflow was stopped for 20 s at intrasinus pressures of 50, 125, and 200 mmHg. Zero-flow arterial pressures under condition 1 were 16.2 +/- 1.3 (SE), 13.8 +/- 1.1, and 12.5 +/- 0.8 mmHg, respectively. In condition 2, the venous outflow tube was clamped at the instant of stopping the inflow, causing venous pressure to rise. The zero-flow arterial pressures were 19.7 +/- 1.3, 18.5 +/- 1.4, and 16.4 +/- 1.2 mmHg for intrasinus pressures of 50, 125, and 200 mmHg, respectively. At all levels of intrasinus pressure, the zero-flow arterial pressure in condition 2 was higher (P less than 0.005) than in condition 1. In seven dogs, at an intrasinus pressure of 125 mmHg, epinephrine increased the zero-flow arterial pressure by 3.0 mmHg, whereas hexamethonium and papaverine decreased the zero-flow arterial pressure by 2 mmHg. Reductions in the hematocrit from 52 to 11% resulted in statistically significant changes (P less than 0.01) in zero-flow arterial pressures. Thus zero-flow arterial pressure was found to be affected by changes in venous pressure, hematocrit, and vasomotor tone. The evidence does not support the literally interpreted concept of the vascular waterfall as the model for the finite arteriovenous pressure difference at zero flow.     

Effects of bradykinin and papaverine on renal autoregulation and renin release in the anaesthetized dog.

The present study on six anaesthetized dogs investigates the influences of two different vasodilators, bradykinin and papaverine, on the relationship between autoregulation of renal blood flow and glomerular filtration rate, sodium excretion and renin release. At control conditions renal blood flow and glomerular filtration rate was autoregulated to the same levels of renal arterial pressure, 55 +/- 3 and 58 +/- 3 mmHg, respectively. Renin release increased from 0.3 +/- 0.1 to 22 +/- 4 micrograms AI min-1, and sodium excretion decreased from 99 +/- 29 to 4.6 +/- 3.3 mumol min-1 when renal arterial pressure was reduced from 122 +/- 6 to 44 +/- 2 mmHg. Infusion of bradykinin (50 ng kg-1 min-1) increased renal blood flow by 50% at control blood pressure without changing glomerular filtration rate, and both renal blood flow and glomerular filtration rate autoregulated to the same pressure levels as during control. Sodium excretion increased threefold at control renal arterial pressure, but was unchanged at low renal arterial pressure. Bradykinin did not change renin release neither at control nor low renal arterial pressure. Papaverine infusion at a rate of 4 mg min-1 increased renal blood flow 50% without changing glomerular filtration rate. The lower pressure limits of renal blood flow and glomerular filtration rate autoregulation were increased to 94 +/- 6 and 93 +/- 6 mmHg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

The venous hypothesis of hydrocephalus

Pressure in the central nervous system (CNS) depends upon the volume of tissue that it contains. This includes blood, cerebrospinal fluid (CSF), nerves and any space occupying lesions. The dependency of pressure on volume arises because the CNS is confined by bone. Venous and CSF pressure is linked to overall pressure. Arterial pressure can increase in response to overall pressure to maintain arterial supply. Continuous arterial supply can be maintained because venous blood flows out of the CNS. Reduced volumes of arterial blood will enter the system if venous outflow is interrupted. Increase in CNS volume, as occurs with space occupying lesions, causes compression of veins. This may result in increased venous pressure and reduction in flow of blood out of the CNS. Cerebrospinal fluid (CSF) is extracellular fluid; its absorption back into the circulation is influenced by venous pressure. Any increased in CNS tissue volumes can therefore lead to CSF accumulation. This may then exacerbate the hydrocephalus by further increasing overall CNS volume. Free flow of CSF around the CNS facilitates venous drainage. Blockages to CSF flow can act like space occupying lesions. Chiari malformations, where the cerebellar tonsils obstruct the foramen magnum lead to reductions in CSF flow that can occur intermittently. This leads to impairment of venous drainage which may result in accumulation of CSF. The head or the spine can be affected together or separately. The manifestation of excess fluid accumulation is hydrocephalus and syringomyelia. The speed and origin of venous insufficiency influences the morphology of individual cases particularly with regard to lateral ventricle size. When pressure increases rapidly there may be little time for CSF accumulation. Oedema, compression of intracranial CSF spaces and cerebral ischaemia follows. When venous pressure is only slightly elevated CSF will accumulate and the manifestations of ischaemia may be less apparent, although ischaemia will be a feature of all instances of pathologically raised CNS pressure.     

Renin release and autoregulation of blood flow in a new model of non-filtering non-transporting kidney.

1. A recently developed model of a non-filtering, non-transporting dog kidney, obtained by an in situ filling of tubules with low-viscosity oil, was applied for studies of renin release and autoregulation of renal blood flow (RBF). 2. Renal blood flow was partially autoregulated after oil blockade of tubules, as indicated by a mean autoregulation index (Semple-de Wardener (1959) of 0-5. This was comparable to autoregulation of the stop-flow kidney (index 0-6) and contrasted with abolition of autoregulation after hypertonic mannitol loading at stop-flow conditions (index 1-1). 3. The aortic construction at a suprarenal level, which decreased renal perfusion pressure of the oil-blocked kidney 35 +/- (S.E. of mean) 6 mmHg, produced an increase in arterial plasma renin activity of 1-8 +/- 0-1 ng. ml.-1 (P less than 0-02). Renin secretion rate decreased 33 to 70 ng.min-1 in three dogs in which renal perfusion pressure was reduced to 60--66 mmHg, but increased 110 +/- 41 ng.min-1 when pressure reductions were kept within the renal blood flow autoregulation range (n=8, P less than 0-025). 4. These results suggest that signals from the tubular receptor (macula densa) are not necessary for stimulation of renin release or autoregulation of renal blood flow.     

Effect of chronic sympathetic denervation upon the transcapillary filtration rate induced by venous stasis

The effect of venous pressure elevation upon capillary filtration rate in the limb was studied in 6 chronically sympathectomized patients. Five healthy subjects served as controls. Volume changes of the forearm or calf were recorded by a strain-gauge plethysmograph. Relative blod flow in subcutaneous and muscle tissue during venous stasis was measured by the local ¹³³Xe washout technique. In the denervated limbs there was a linear relationship between net capillary filtration rate and venous pressure elevation. In the controls a non-linear relationship was seen as venous pressure elevation of 40 mmHg only caused an increase in net filtration rate of about 66% of that expected from a linear relationship. In the denervated limbs blood flow in muscle and subcutaneous tissue remained constant during venous pressure elevation of more than 30 mmHg whereas in the non-denervated limbs blood flow decreased by about 50% in both tissues. The results suggest that a local sympathetic veno-arteriolar (axon) reflex plays a dominant role for the reduced increase in net capillary filtration rate during large increases in venous pressure. The local axon reflex may therefore act as an edema protecting factor.     

Intramural blood flows and flow distribution in the feline small intestine during arterial hypotension

The vascular reactions of the parallel-coupled vascular sections of the small intestine were studied during hypotension at two different levels of intestinal arterial inflow pressure, using a 85Kr elimination technique. The regional hypotension was accomplished by partially occluding the superior mesenteric artery with a clamp and maintained for 2 h. At the higher level (50-55 mmHg) total intestinal blood flow decreased but not to the same relative extent as blood pressure due to the autoregulatory capacity of the intestinal vascular bed. The flow autoregulation was also reflected in a decreased blood flow resistance. The distribution of blood to the muscularis and mucosa-submucosa layer, respectively, did not change significantly during or after hypotension as compared to the prehypotensive level, since the relative flow decrease was the same in the mucosa-submucosa and in themuscularis. At the lower arterial pressure level (30-35 mmHg) a more marked decrease of intestinal blood flow and flow resistance was observed as compared to the experiments performed at the 50-55 mmHg pressure level. Moreover, muscularis blood flow was relatively more decreased than blood flow in the mucosa-submucosa implying the fraction of total blood flow diverted to the muscularis was significantly decreased. Despite this redistribution of blood flow, a histological damage was apparent only in the mucosa, particularly at the villous tips.     

Right ventricular coronary blood flow patterns during aortic pressure reduction in renal hypertensive dogs.

We measured right ventricular coronary blood flow with radioactive microspheres during graded aortic pressure reduction in 13 normal dogs and in 13 renal hypertensive dogs with left ventricular hypertrophy. Under anaesthesia and controlled loading conditions, mean aortic pressure was lowered from control (128 mmHg in normal and 146 mmHg in hypertensive dogs) to approximately 100, 90 and 80 mmHg. In normal dogs, right ventricular blood flow was not affected by this pressure reduction, consistent with effective right ventricular autoregulation. In hypertensive dogs, however, right ventricular blood flow was maintained between a mean aortic pressure of 146 and 90 mmHg (range 75-79 ml min(-1) 100 g(-1] but fell by 18% to 63 ml min 100 g(-1) at a mean aortic pressure of 80 mmHg (P less than 0.005). We conclude that autoregulation of right ventricular blood flow was preserved in chronic hypertension but that, compared to normal dogs, the lower limit of autoregulation was reset to a higher pressure level. Moreover, the similarity of right ventricular-to-body weight ratios in the two groups implied that this change was a consequence of hypertension-induced structural changes in the coronary vasculature.     

Autonomic dysfunction: A unifying multiple sclerosis theory,linking chronic cerebrospinal venous insufficiency,vitamin D3, and Epstein-Barr virus

Multiple sclerosis (MS) is a disease with multiple etiologies. The most recent theory of the vascular etiology of MS, Chronic Cerebrospinal Venous Insufficiency (CCSVI), suggests that cerebral venous obstruction could lead to cerebral venous reflux, promoting local inflammatory processes.This review article offers strong evidence that the route of the observed narrowing of cerebral veins arises from autonomic nervous system dysfunction, particularly cardiovascular autonomic dysfunction.The dysfunction of this system has two major effects: 1) the reduction of mean arterial blood pressure, which has the potential to reduce the cerebral perfusion pressure and the transmural pressure, and 2) the failure of cerebral autoregulation to maintain constant cerebral blood flow in the face of fluctuations in cerebral perfusion pressure. Alterations in cerebral autoregulation could in turn raise the critical closure pressure, indicated to be the cerebral perfusion pressure at which the transmural pressure will be sub-sufficient to overcome the active tension imparted by the smooth muscle layer of the vessel. These two effects of autonomic nervous system dysfunction (reduction in arterial blood pressure and alterations in cerebral autoregulation), when combined with inflammation-induced high levels of nitric oxide in the brain, will lower transmural pressure sufficiently to the point where the threshold for critical closure pressure is reached, leading to venous closure.In addition, cerebral vessels fail to overcome the closure as a result of low central venous pressure, which is also regulated by autonomic nervous system function. Furthermore, through their neuroregulatory effects, infectious agents such as the Epstein-Barr virus and vitamin D₃ are able to alter the functions of the autonomic nervous system, influencing the rate of CCSVI occurrence.The absence of CCSVI specificity for MS, observed in recent clinical studies, may stem from a high prevalence of autonomic nervous system dysfunction in control groups which were recruited to these studies. Future studies should investigate CCSVI in relation to cardiovascular autonomic function.     

Sympathetic reflex-induced vasoconstriction during renal venous stasis elicited from the capsule in the dog kidney

The study was performed in order to determine the effect of venous pressure elevation induced by unilateral partial renal venous ligation upon total renal blood flow and filtration fraction in the dog kidney. An anaesthesia with no known inhibitory effect on sympathetically mediated vasoconstriction was used. During control conditions instantaneous increase in renal venous pressure to 60 mmHg induced a decrease in renal blood flow (66 +/- 4%) corresponding to an ipsilateral vasoconstriction which was completely abolished following (1) surgical denervation of the kidney, (2) local alpha-receptor blockade of the kidney, and (3) application of lidocaine on the kidney surface. The most striking feature during step increase in renal venous pressure to 40 mmHg was an increase in renal vascular conductance. Renal venous pressure elevation of more than 40 mmHg induced a vasoconstriction, but the vasoconstrictor response was less pronounced as compared with that observed during instantaneous increase in renal venous pressure to the same level. The results strongly suggest that venous stasis of more than 40 mmHg activates an adrenergic sympathetic vasoconstrictor reflex comprising the spinal cord. The reflex is probably elicited from stretch receptors located in the renal capsule. Changes in filtration fraction at venous stasis during the experimental conditions indicate that renal venous pressure elevation activates mechanisms other than neural ones accounting for the reduction in the filtration fraction.     

Right ventricular coronary blood flow patterns during aortic pressure reduction in renal hypertensive dogs

We measured right ventricular coronary blood flow with radioactive microspheres during graded aortic pressure reduction in 13 normal dogs and in 13 renal hypertensive dogs with left ventricular hypertrophy. Under anaesthesia and controlled loading conditions, mean aortic pressure was lowered from control (128 mmHg in normal and 146 mmHg in hypertensive dogs) to approximately 100, 90 and 80 mmHg. In normal dogs, right ventricular blood flow was not affected by this pressure reduction, consistent with effective right ventricular autoregulation. In hypertensive dogs, however, right ventricular blood flow was maintained between a mean aortic pressure of 146 and 90 mmHg (range 75–79 ml min^-1 100 g^-1) but fell by 18% to 63 ml min 100 g^-1 at a mean aortic pressure of 80 mmHg (P < 0.005). We conclude that autoregulation of right ventricular blood flow was preserved in chronic hypertension but that, compared to normal dogs, the lower limit of autoregulation was reset to a higher pressure level. Moreover, the similarity of right ventricular-to-body weight ratios in the two groups implied that this change was a consequence of hypertension-induced structural changes in the coronary vasculature.     

Hemodynamics of the juvenile dog knee in relation to increased venous outlet resistance

Tissue blood flow was measured by the tracer microsphere technique in the juxta-articular bones of the immature knee, knec joint capsule and skeletal muscles of the hind limbs after unilateral bone cannulation of the distal femoral epiphysis, surgical exploration of the popliteal vessels and unilateral isolated increase of venous outlet resistance in the distal femoral epiphysis during Halothane anaesthesia. Pressure registration was performed in a liquid-filled electromanometric pressure recording system. Significant regional differences in bone blood flow was found within the different bone compartments of both control and test limb. Bone cannulation resulted in insignificant hyperaemia in the distal femoral epiphysis. No changes of distribution pattern of bone blood flow followed the surgical procedure. Ligation of the medial genicular vein caused a three fold increase of venous outlet resistance measured after 5 min, while an insignificant decrease of arterial inlet resistance was calculated. After one hour a significant decrease of both arterial inlet resistance and venous outlet resistance was found. In addition evidence of a veno-arterial reflex mechanism causing a significant unilateral decrease of distal skeletal muscle blood flow was found. The results demonstrate the presence of both venous and arterial regulation, predominantly metabolic, of bone blood flow in the knee.     

Regional,segmental, and temporal heterogeneity of cerebral vascular autoregulation

Autoregulation of cerebral blood flow is heterogeneous in several ways: regional, segmental, and temporal. We have found regional heterogeneity of the autoregulatory response during both acute reductions and increases in systemic arterial presure. Changes in blood flow are less in brain stem than in cerebrum during decreases and increases in cerebral perfusion pressure. Segmental heterogeneity of autoregulation has been demonstrated in two ways. Direct determination of segmental cerebral vascular resistance indicates that, while small cerebral vessels (<200 μm in diameter) make a major contribution to autoregulation during acute increases in pressure between 80 and 100 mm Hg, the role of large cerebral arteries (>200 μm) becomes increasingly important to the autoregulatory response at pressures above 100 mm Hg. Measurement of changes in diameter of pial vessels has shown that, during acute hypotension, autoregulation occurs predominantly in small resistance vessels (<100 μm). Finally, there is temporal heterogeneity of autoregulation. Sudden increases in arterial pressure produce transient increases in blood flow, which are not observed under steady-state conditions. In addition, the blood-brain barrier is more susceptible to hypertensive disruption after rapid, compared to step-wise, increases in arterial pressure. Thus, when investigating cerebral vascular autoregulation, regional, segmental, and temporal differences in the autoregulatory response must be taken into consideration.     

Effects of bradykinin and papaverine on renal autoregulation and renin release in the anaesthetized dog

The present study on six anaesthetized dogs investigates the influences of two different vasodilators, bradykinin and papaverine, on the relationship between autoregulation of renal blood flow and glomerular filtration rate, sodium excretion and renin release. At control conditions renal blood flow and glomerular filtration rate was autoregulated to the same levels of renal arterial pressure, 55 ± 3 and 58 ± 3 mmHg, respectively. Renin release increased from 0.3±0.1 to 22±4 μg AI min^-1, and sodium excretion decreased from 99 +29 to 4.6 ± 3.3 μmol min^-1 when renal arterial pressure was reduced from 122±6 to 44±2 mmHg. Infusion of bradykinin (50 ng kg^-1 min^-1) increased renal blood flow by 50% at control blood pressure without changing glomerular filtration rate, and both renal blood flow and glomerular filtration rate autoregulated to the same pressure levels as during control. Sodium excretion increased threefold at control renal arterial pressure, but was unchanged at low renal arterial pressure. Bradykinin did not change renin release neither at control nor low renal arterial pressure. Papaverine infusion at a rate of 4 mg min^-1 increased renal blood flow 50% without changing glomerular filtration rate. The lower pressure limits of renal blood flow and glomerular filtration rate autoregulation were increased to 94±6 and 93±6 mmHg, respectively. Sodium excretion increased sixfold at control renal arterial pressure and was still as high as the initial control values at low renal arterial pressure (97±27 μmol min^-1) accompanied by only a small increase in renin release (1.4±0.3 to 6±2 μg AI min^-1). We conclude that bradykinin does not influence autoregulatory pressure limits of renal blood flow and glomerular filtration rate nor the accompanying increase in renin release during reductions in renal arterial pressure. Papaverine on the other hand maintains high sodium chloride delivery to macula densa at low renal arterial ressure, suppressing renin release and impairing autoregulation through effects on the tubulo-glomerular feedback mechanism.