Beta 2-adrenergic attenuation of capillary pressure autoregulation during haemorrhagic hypotension, a mechanism promoting transcapillary fluid absorption in skeletal muscle.

The aim of this study was to evaluate a possible humoral beta 2-adrenergic effect on the capillary pressure autoregulation capacity in cat skeletal muscle during bleeding. For this purpose capillary pressure autoregulation in response to graded decrease in arterial pressure was studied in sympathectomized muscle in the control state, and during haemorrhagic hypovolaemia in the presence and absence of selective beta 2-adrenoceptor blockade (ICI 118,551). The study was performed with a technique that permits continuous recordings of average capillary pressure in absolute terms and of the regional pre- and postcapillary vascular resistance, from which the pre- to post capillary resistance ratio could be determined. In the pre-haemorrhagic control state, an experimental decrease in arterial pressure from 100 to 50 mmHg caused a fall of capillary pressure from 17.6 by only 1.7 mmHg (delta PA/delta Pc = 29), demonstrating an efficient capillary pressure autoregulation. This autoregulation was accomplished by a decrease in pre- to post capillary resistance ratio in turn being a result of active precapillary dilatation and a passive increase in post capillary vascular resistance. Haemorrhage per se, via a humoral alpha-adrenergic preferentially precapillary vasoconstriction, caused a decrease in capillary pressure to 16.8 mmHg at arterial pressure 100 mmHg. A superimposed decrease in arterial pressure to 50 mmHg resulted in a capillary pressure fall by 3.7 mmHg (delta PA/delta Pc = 14), indicating impaired auto-regulation capacity. This attenuation to a great extent could be ascribed to adrenaline-induced B2-adrenoceptor stimulation, since beta 2-blockade restored the delta arterial pressure/capillary pressure ratio to 20. Low-dose isoprenaline infusion in the control state similarly caused marked impairment of capillary pressure autoregulation. The beta 2-adrenergic attenuation of capillary pressure autoregulation appears to be a beneficial effect in haemorrhagic hypotension, since it lowers capillary pressure passively in relation to the arterial pressure fall, thereby reinforcing the alpha-adrenergic active capillary pressure decrease, leading to more effective transcapillary fluid absorption and, hence, improved replenishment of plasma volume.     

Effect of alveolar hypoxia on segmental pulmonary vascular resistance and lung fluid balance in dogs

In a biventricular bypass preparation with constant-flow perfusion, pulmonary arterial pressure (P_pa), average pulmonary capillary pressure (P_pc), venous pressure (P_v), extravascular lung water volume (EVW_d) and capillary permeability-surface area product for urea (PS) were determined in control animals and in animals subjected to alveolar hypoxia. During hypoxia, P_pa increased in a biphasic manner, the site of hypoxic pulmonary vasoconstriction being located in the arterial upstream segment. At baseline, P_pc values were identical in control and experimental animals (3.4 ± 0.4 vs. 3.6 ± 0.2 mmHg). During 150 min of airway hypoxia, the rise in P_pc (5.1 ± 0.3mmHg) did not exceed the rise in P_pc (4.9 ± 0.5mmHg) recorded in control animals at same time interval during normoxic ventilation. EVW_d increased during hypoxia to values significantly higher than those obtained in control animals (0.559 ± 0.036 vs. 0.466 ± 0.027 mL water g^?1 lung). PS remained unchanged at baseline level throughout experiments in both groups of animals. Present data suggest that lung oedema formation during alveolar hypoxia may be caused by increased transcapillary fluid loss preferentially through transcellular hydraulic pathways in capillary endothelial cells.     

Fluid transfer from skeletal muscle to blood during hemorrhage Importance of beta adrenergic vascular mechanisms

Vascular reactions in the cat lower leg muscles in response to short-term (10 min) hemorrhagic hypotension (?80 mmHg) were studied before and after regional blockade of the β-adrenoceptors. In the muscle region with intact β-adrenoceptors, hemorrhage raised vascular resistance by about 80% and caused a dilatation of the precapillary sphincters, the latter effect evidenced in terms of a 35% increase of the capillary filtration coefficient. Concomitantly, an absorption of extravascular fluid to the blood stream occurred, a process tending to compensate for the reduction of intravascular fluid volume. After regional β-blockade there was quite a marked augmentation of the hemorrhage induced increase of vascular resistance whereas the inhibition of precapillary sphincter tone and the transcapillary fluid absorption were almost abolished. These observations indicate that bleeding is associated with a significant β-adrenergic dilator influence in both the resistance vessels and precapillary sphincters of skeletal muscle and that the β-dilator mechanism may be essential for the important, compensatory fluid gain from the extravascular to the intravascular space during hemorrhage. The observed β-adrenergic mediation of the net transcapillary fluid absorption could be ascribed to resetting of the pre-/postcapillary resistance ratio, leading to decreased capillary hydrostatic pressure, and to the dilator influence in the precapillary sphincters, leading to an increased number of the patent capillaries available for the transcapillary fluid exchange.     

Central hemodynamic effects of adrenaline with special reference to β2-adrenergic influence on heart rate and cardiac afterload in anesthetized cats

Central hemodynamic responses evoked by i. v.infusions of adrenaline and noradrenaline were studied in normovolemic anesthetized cats with intact adrenoceptors, after selective β₂-blockade (ICI 118,551), and after nonselective β-blockade (propranolol).The results demonstrated the presence of an important β₂-adrenergic component in the integrated response to ‘physiological’ doses of adrenaline contributing to increased cardiac output, decreased total peripheral resistance and virtually unchanged mean arterial blood pressure. Corresponding β₂-adrenergic effects of noradrenaline were small. The β₂-adrenergic effects of adrenaline on the heart seemed to be both direct and indirect. A moderate direct chronotropic response mediated by β₂-adrenoceptors apparently was present but there was no evidence of a direct β₂-adrenergic inotropic effect. An indirect, quite marked effect on the heart was accomplished by a β₂-adrenergic vasodilator interaction with the α-adrenergic vasoconstrictor influence on the systemic resistance vessels. This caused a net decrease in total peripheral resistance, thereby preventing an undue increase in cardiac afterload (arterial pressure) which seemed to be essential for evoking ‘optimal’ increases in cardiac output. It is suggested that such adrenaline evoked indirect, β₂-adrenergic improvement of cardiac performance is of functional importance in reflex sympatho-adrenal circulatory control.     

Metabolic control of large-bore arterial resistance vessels,arterioles, and veins in cat skeletal muscle during exercise

The metabolic control of the vascular bed in cat gastrocnemius muscle during exercise was studied with a new technique (Björnberg et al. 1988) permitting continuous and simultaneous recordings of arteriolar and capillary pressures, and of resistances in the following consecutive vascular section: proximal arterial resistance vessels > 25 μm, arterioles < 25 μm, and on the venous side. The study thereby provided quantitative data for resistance and active intrinsic tone in these vascular segments at rest, during graded exercise vasodilatation, and in the post-exercise period. Slight activation of the metabolic control system by low-frequency somatomotor nerve stimulation (light exercise') caused inhibition of intrinsic tone and decreased vascular resistance selectively in the arteriolar section. At increasing workloads, arteriolar resistance was further decreased, but resistance and tone in the proximal arterial resistance vessels and the veins then became clearly reduced as well. This difference in effectiveness of the metabolic control system on the different segments of the vascular bed was expressed quantitatively in terms of a ‘metabolic vasodilator index’. Graded activation of the metabolic control system led to a marked segmental redistribution of intrinsic vascular tone, in turn resulting in an increased pressure drop across the proximal arterial vessels and the veins and a decreased pressure drop over the arterioles. The observed decrease in the pre- to post-capillary resistance ratio caused, at a constant arterial pressure of 100 mmHg, a graded increase in capillary pressure with increasing workloads, at maximum vasodilatation by an average value of 14 mmHg above the resting control value of 15.4 ± 0.6 mmHg. In the post-exercise period, recovery of vascular tone to control was more rapid in the proximal arterial resistance vessels and the veins than in the arteriolar segment.     

Beta Adrenergic Dilator Component of the Sympathetic Vascular Response in Skeletal Muscle Influence on the micro-circulation and on transcapillary exchange

A neurogenic β-adrenergic vasodilatation in skeletal muscle has been indicated by some recent investigations. The present study describes the extent to which this neurogenic β-dilator mechanism contributes to the integrated vascular response in consecutive sections of the muscle vascular bed during sympathetic nerve activation. This was done by studying the vascular reactions to graded sympathetic stimulation (1–16 Hz) before and after β-adrenoceptor blockade, β-blockade did not influence significantly the sympathetically induced changes of total muscle vascular resistance or capacitance. Vascular tone in the “micro-vessels” during stimulation was, however, clearly more pronounced in the β-blocked than in the non-blocked region, as revealed by segmental resistance analysis and by determination of precapillary sphincter tone (CFC). In addition, β-blockade markedly reduced the net transcapillary absorption of extravascular fluid evoked by nerve activation. This effect could be ascribed to the mentioned influence on the precapillary sphincters, leading to a decrease of the number of capillaries available for transcapillary exchange, and to a limitation of the nerve induced fall of capillary hydrostatic pressure. The described effects of β-blockade were observed at all rates of sympathetic stimulation. — The conclusion was reached that the β-adrenergic dilator component of the sympathetic vascular response in skeletal muscle significantly modifies the α-adrenergic constriction in the micro-vessels. It is suggested that, in the intact organism, this neurogenic β-dilator mechanism is primarily aimed at improving the transcapillary exchange.     

Classification of β-adrenoceptors in the microcirculation of skeletal muscle

Nervous and humoral β-adrenergic, postjunctional effects on microvascular resistance, on precapillary sphincter tone, and on transcapillary fluid exchange in cat skeletal muscle (Lundvall & Järhult 1974, 1976 a, Lundvall & Hillman 1978 a, b) were evaluated with regard to the β₁-or β₂,-specificity of the adrenoceptors. Marked β₂-dilator responses but no significant β₁-effects were observed. The conclusion was therefore reached that neurogenic as well as humoral β-adrenergic control of the microcirculation in skeletal muscle is exerted via activation of β₂-adrenoceptors.     

Noninvasive method for estimating the mean capillary pressure and pre- and postcapillary resistance ratio in human fingers

A noninvasive method for estimating the mean capillary pressure P_cap and the pre-and postcapillary resistance ratio R_v/R_a in human fingers is described. Volume change in a finger segment was detected with a transmittance-type infra-red photoelectric plethysmograph during a gradual and linear increase in occluding cuff pressure. There was an inflection point in the volume curve which would be produced by the difference in the compliance between the arterial and venous vascular bed in the segment. This transitional point was assumed to represent the complete compression of the venous vascular bed at the cuff pressure level. Thus P_cap was defined as the cuff pressure corresponding to the inflection point. R_v/R_a was calculated from the P_cap, the venous pressure P_v and the mean arterial pressure P_am. The latter two pressures, P_v and P_am, were also indirectly and simultaneously measured by the compression pressure of another cuff and by our new type of volume oscillation method, respectively. The values of P_cap and R_v/R_a were in good agreement with those reported by other investigators.     

β2-adrenergic control of plasma volume in hemorrhage

Hemorrhage is associated with absorption of extravascular fluid from skeletal muscle to blood in order to compensate for the loss of intravascular volume. Our previous studies have shown that this fluid gain is mainly linked to β-adrenergic microvascular adjustments leading to decrease in capillary hydrostatic pressure and to precapillary ‘sphincter’ mediated increase in the capillary surface area available for fluid exchange. In the present study the importance of β-adrenergic control of plasma volume in bleeding was confirmed by measurement of changes in plasma volume after graded hemorrhage in animals with intact and blocked vascular β₂-adrenoceptors (i. v. administration of the ‘selective’β₂-blocking agent ICI 118, 551). With intact β₂-adrenoceptors plasma volume was gradually restored after bleeding so that about 50% of the shed plasma volume (about 35% of the shed blood volume) had been compensated for at two hours after exsanguination of 20% as well as 40% of the blood volume. The corresponding figures in animals with blocked β₂-adrenoceptors were only 14% of the shed plasma volume and 8% of the shed blood volume at both degrees of hemorrhage.     

Reduced permselectivity in isolated perfused rat kidneys following small elevations of glomerular capillary pressure

A modified rat kidney preparation was used to explore how changes in hydrostatic pressure affect the permselective properties of the glomerular capillary bed. Th? maximally vasodilated kidneys of 18 rats were perfused with albumin solutions (16.7 g ^-1) at different flow rates and hence arterial pressures (P_A). One kidney in each rat was exposed to pressure elevations with the other kidney serving as a control perfused at constant P_A of about 100 mmHg. Both the vascular resistance to flow and the glomerular filtration rate (GFR 34.6 ± 2.9 ml min¹ 100 g^_1) were similar in the two kidneys at equal P_A and remained constant throughout the experiment. The ratio of albumin clearance over GFR (Θ) was initially around 0.4% at constant P_A and gradually increased during 1.5 h to reach 0.7% at the end of the experiment. A direct increase of P_A from 100 to 200 mmHg for 15 min resulted in a calculated increase of the effective glomerular filtration pressure gradient of 10–15 mmHg and in a two-fold increase ofΘ when measured at an identical P_A of 100 mmHg. Albumin clearance was almost fully normalized within 20 min similar to that observed in e.g. skeletal muscle. However, the glomerular capillary barrier seemed to be far more sensitive to elevations of hydrostatic pressure than other capillary walls which require capillary pressure increments of 60 mmHg in order to induce similar reversible changes in permeability. Therefore, we conclude that an elevated P_G:c per se induces changes of glomerular permselectivity, which may have important pathophysiological implications during conditions of proteinuria.     

Effect of single-leg resistance exercise on regional arterial stiffness

To examine the effects of lower-limb unilateral resistance exercise on central and peripheral arterial stiffness, thirteen participants (7 male and 6 female, mean age = 21.5 ± 0.7 years) performed leg press exercise using their dominant leg. Pulse wave velocity (PWV) was used to measure central (carotid to femoral) and peripheral (femoral to dorsalis pedis of both legs) arterial stiffness before, 5 min post, and 25 min post exercise. No change was found in central PWV. A leg-by-time interaction was found as peripheral PWV in the non-exercised leg did not change (7.9 ± 0.3 m/s to 7.9 ± 0.3 m/s to 8.0 ± 0.3 m/s, P = 0.907) while peripheral PWV in the exercised leg significantly decreased from pre (8.7 ± 0.4 m/s) to 5 min post exercise (7.5 ± 0.3 m/s, P = 0.008) and 25 min post exercise (7.8 ± 0.3 m/s, P = 0.031). Systolic blood pressure (BP) increased significantly from pre (126.9 ± 3.4 mmHg) to 5 min post exercise (133.7 ± 4.3 mmHg, P = 0.023) and was not different than resting values 25 min post exercise (123.2 ± 3.1 mmHg). There was no change in diastolic BP. Compared to heart rate (HR) pre-exercise (55.4 ± 1.4 bpm), HR was significantly increased 5 min post exercise (70.7 ± 3.0 bpm, P = 0.001) and 25 min post exercise (69.1 ± 2.0, P = 0.001). Acute resistance exercise appears to decrease arterial stiffness in the exercised leg while having no effect on central arterial stiffness or arterial stiffness of the non-exercised leg. These findings suggest that regional changes rather than systemic alterations may influence arterial stiffness following acute resistance exercise.     

Hormonal and neurogenic adrenergic control of the fluid transfer from skeletal muscle to blood during hemorrhage

During hemorrhage net transcapillary absorption of interstitial fluid from skeletal muscle into the intravascular space compensates effectively for the blood loss. This absorption of fluid is mainly linked to decrease of the capillary hydrostatic pressure (Pc), as caused by reflex adrenergic re-adjustment of the ratio of pre-to postcapillary resistance (ra/rv). The present study demonstrates the existence of both a neurogenic and a humoral component in the adrenergic control of the fluid transfer from skeletal muscle to blood. In the early period of bleeding (<5 min) reflex activation of the vasomotor fibres contributed significantly to the fluid absorption. The subsequent, main part of the fluid gain from the extra-to the intravascular space was due to the action of the blood-borne catecholamines. Both the neurogenic and the hormonal control of the fluid absorption process was mainly linked to β-adrenergic inhibition of vascular smooth muscle tone. This control was effected via two mechanisms, viz. by a relatively larger β-adrenergic dilatation of post-than precapillary resistance vessels, leading to adjustment of ra/rv and thereby to decrease of Pc, and via β-adrenergic dilatation of ‘precapillary sphincters’ leading to increased capillary surface area available for fluid exchange.     

Loci of Neurogenic and Metabolic Effects on Precapillary Vessels of Skeletal Muscle

Folkow , B., R. R. Sonnenschein , and D. L. Wright , Loci of neurogenic and metabolic effects on precapillary vessels of skeletal muscle. Acta physiol. scand. 1971. 81. 459–471. By cannulation of a branch of the proximally clamped sural artery of the anesthetized cat, distal arterial pressure (DAP) in the gastrocnemius muscle was recorded. Measurement of blood flow, femoral arterial pressure and DAP allowed calculation of total resistance (R_t) and its partition into a distal component (R_d) which included precapillary sphincters and the smaller arterioles, and a proximal component (R_P) which included the larger arteries. With sympathetic vasoconstriction, the initial increase in R_t was accounted for mainly by constriction of the distal vessels which then tended to relax; progressive constriction of proximal vessels accounted for most of the elevated R_t during the steady state; subsequent reactive hyperemia mainly involved distal vessels. R_t was less affected by sympathetic stimulation during exercise than when the muscle was at rest; constriction of distal vessels was more markedly reduced than that of proximal vessels. Ascending dilatation was evident during exercise. Sympathetic cholinergic vasodilatation mainly involved vessels more proximal to those which were dilated early in exercise. The findings are compatible with the concept that capillary flow distribution, as a function of terminal arterioles and precapillary sphincters, is adjusted by local factors towards an optimum for the prevailing metabolic level of the tissue.     

Segmental distribution of vascular resistances during ureteral occlusion: The vasoconstrictive effects of angiotensin and CaCl2 differ from those of catecholamines and renal nerve stimulation

Examinations of renal autoregulation and renin release suggest that α-adrenergic agonists, in contrast to other vasoconstrictors, preferentially constrict the preglomerular arteries. To examine this hypothesis, experiments were performed in anesthetized dogs during ureteral occlusion. At a ureteral pressure (UP) of 100 mmHg the afferent arterioles are dilated and mechanical constriction of the renal artery does not alter intrarenal vascular resistances. Whereas angiotensin and CaCl₂ infused into the renal artery reduced renal blood flow (RBF) by 25–30% without reducing UP, renal nerve stimulation reduced RBF and UP in proportion. During angiotensin and catecholamine infusion, measurements of UP and intrarenal venous pressure permitted calculations of preglomerular, efferent vascular and intrarenal venous resistances. Until RBF was reduced by 25%, angiotensin raised both preglomerular and efferent vascular resistances, whereas norepinephrine and the α-adrenergic agonists, phenylephrine and methoxamine raised preglomerular more than efferent vascular resistance. When RBF was reduced by more than 25%, all vasoconstrictors showed a similar pattern with large increments both in preglomerular and efferent vascular resistances. Conclusions: Humoral and nervous stimulation of α-adrenergic receptors reduce glomerular capillary pressure by preferentially constricting the preglomerular arteries and may affect renal autoregulation and renin release by reducing the transmural pressure of the afferent arterioles.     

Acute ventilation-perfusion mismatching resulting from inhalative smoking of the first cigarette in the morning

Summary The effect of the first cigarette in the morning on the airway resistance (R _aw) which can be measured by body-plethysmography was investigated in 70 inhaling cigarette smokers. The test population showed a significant (P<0.0005) fall in R _aw 8 min after smoking. A further study (n = 16) showed that the fall in R _aw was most likely to be attributable to a decrease in the trapped air. The effect of the first cigarette in the morning on the arterial blood gases and on the alveolar-arterial oxygen difference P(A-a)O₂ and carbon dioxide difference P(A-a)CO₂ was investigated in 12 inhaling cigarette smokers. Smoking gave rise to a significant (P < 0.0005) fall in the partial pressure of oxygen (PaO₂) with compensatory overventilation. At the same time, the P(A-a)O₂ and the P(A-a)CO₂ increased significantly (P<0.01 and P<0.05, respectively). This effect could be observed for up to 24 min after smoking. In addition, the flow of blood in the pulmonary capillaries was measured in 28 test subjects with the nitrous oxide method ( _{N 2O}) before, and 18–22 min after, smoking the first cigarette in the morning. After smoking, there was a significant (P<0.0005) fall in the _{N 2 O} by an average of 11.3%. The decrease in the R _w the fall in the PaO₂ with compensatory overventilation, the increase in P(A-a)O₂ and P(A-a)O₂ and the decrease in the _{N 2 O} are interpreted as manifestations of pronounced acute ventilation-perfusion mismatching induced by smoking.Abbreviations Cdyn dynamic compliance - Cdyn 40a dynamic compliance at 40 breaths/min - _{N 2}O pulmonary capillary blood flow measured by the N₂O method - P(A-a)a alveolararterial pressure difference - Pa arterial partial pressure - P _AOa alveolar pressure difference measured in the pressure-flow curve at zero flow - R _awa airway resistance - sGaw specific airway conductance - SVI stroke volume index - TGV thoracic gas volume - BSA body surface area     

Sympathetic influence on cardiovascular responses to sustained head-up tilt in humans

Sympathetic β-adrenergic influences on cardiovascular responses to 50d? head-up tilt were evaluated with metoprolol (β₁-blockade; 0.29 mg kg^-1) and propranolol (β₁ and β-₂-blockade; 0.28 mg kg^-1) in eight males. A normotensive-tachycardic phase was followed by a hypotensive-bradycardic episode associated with presyncopal symptoms after 23pL3 min (control, mean pLSE). Head-up tilt made thoracic electrical impedance (3.0pL10Ω), mean arterial pressure (MAP, 86pL4-93pL4 mmHg), heart rate (HR, 63pL3-99pL10 beats min^-1) and total peripheral resistance (TPR, 15pL1-28pL4 mmHg min L^-1) increase, while central venous oxygen saturation (74pL2-58pL4%), cardiac output (5.7pL0.1–3.1pL0.3 L min^-1), stroke volume (95pL6-41pL5 mL) and pulse pressure (55pL4-49pL4 mmHg) decreased (P < 0.05). Central venous pressure decreased during head-up tilt (7pL2-0pL1 mmHg), but it remained stable during the sustained tilt. At the appearance of preswyncopal symptoms MAP (49pL3 mmHg), HR (66pL4 beats min^-1) and TPR (15pL3 mmHg min L^-1) decreased (P < 0.05). Neither metoprolol or propranolo changed tilt tolerance or cardiovascular variables, except for HR that remained at 57pL2 (metoprolol) and 55pL3 beats min^-1 (propranolol), and MAP that remained at 87pL5 mmHg during the first phase with metoprolol. In conclusion, sympathetic activation was crucial for the heart rate elevation during normotensive head-up tilt, but not for tilt tolerance or for the associated hypotension and bradycardia.     

Cerebrovascular responses to haemorrhagic hypotension in anaesthetized cats. Effects of α-adrenoceptor antagonists

Haemorrhagic hypotension induces the phenomenon of cerebrovascular autoregulation and, concomitantly, involves an activation of the sympathetic nervous system. As brain vessels in cats have an atypical adrenoceptor distribution we studied the effects of an a-adrenoceptor antagonist on the autoregulatory response to haemorrhage. Cortical blood flow was studied by the H₂ technique in chloralose-anaesthetized cats subjected to a period of graded haemorrhage over 3 h. Three groups of cats were studied: control, i.e. those receiving saline (n= 10); yohimbine-treated (200/μg^-kg^-1 h^-1, n= 7); and prazosin-treated (50μg-kg^-1 h^-1, n= 6). In the control group, cortical blood flow remained relatively constant when mean arterial pressure was decreased from 102±1 mmHg (mean ± SE) to approximately 50.1 mmHg; thereafter, blood flow decreased with decreasing perfusion pressure. In the arterial pressure range 64-55 mmHg, cortical blood flow was significantly higher in the yohimbine group (109±12 ml-100 g^-1 min^-1) compared to the control group (69 ±6 ml-100 g^-1 min^-1) and remained higher in the yohimbine-treated cats at more extreme levels of hypotension. Blood flow did not fall significantly in the yohimbine-treated cats until mean arterial pressures of 31 ± 1 mmHg were attained. In the prazosin-treated cats, flow began to decrease at arterial pressures even greater than those observed in the control group. Thus, there is a sympathetic vasoconstriction of brain arteries that is primarily mediated by α₂-adrenoceptors in the feline cerebrovascular bed.     

The effect of pressor doses of Angiotensin II on autoregulation and intrarenal distribution of glomerular filtration rate in the rat

This study was designed to investigate the effect of pressor doses of exogenous Angiotensin II (AII) on autoregulation and intrarenal distribution of single nephron glomerular filtration rate (SNGFR) in anesthetized, normotensive rats. SNGFR at all cortical levels of the left kidney was measured with a modified Hanssen technique at three renal arterial pressures (RAP): Spontaneous, 100±1 mmHg and 70±1 mmHg. In control rats, both outer cortical (OC) and inner cortical (IC) nephrons showed complete autoregulation of SNGFR when RAP was redced to 100±1 mmHg. Further reduction to 70±1 mmHg resulted in different responses among the cortical layers, accompanying a decrease in SNGFR.The SNGFR_Ic/SNGFR_oc ratio increased from 1.36±0.053 to 1.52±0.047 and a fractional redistribution of glomerular filtration rate towards IC nephrons was seen. When the kidney was submitted to a RAP of 70±1 mmHg, there was a concomitant increase in central arterial pressure (CAP) from 120±4.3 to 134±3.2 mmHg. A continuous i. v.infusion of All (0.5 μg · min^-1· kg^-1 BW) increased mean arterial pressure from 123±1.4 to 142±3.8 mmHg, an effect corresponding to that on peripheral vascular resistance during reduction of RAP to 70±1 mmHg in control rats. This dose reduced SNGFR at all cortical levels, but did not per se lead to redistribution of SNGFR.A reduction in RAP to 100±1 mmHg during All administration resulted in impaired autoregulation of SNGFR in both OC and IC nephrons. Our results show that exogenous All impairs autoregulation and cannot per se have an effect mimicking the fractional redistribution seen in control rats with a reduction of RAP below the limit for autoregulation. However, in this situation intrarenally formed All may still be of importance for autoregulation and distribution of glomerular filtration rate.     

Resetting of renal autoregulation in conscious dogs: angiotensin II and alpha1-adrenoceptors

It has recently been shown, that common carotid occlusion (CCO) impairs autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR). This study was designed to investigate the mechanisms by which a moderate sympathetic stimulus influences RBF and GFR autoregulation. CCO provided a moderate sympathetic stimulus, and impaired autoregulation by increasing the lower autoregulatory limit of RBF and GFR by 21–30 mmHg. Basal RBF and GFR were not affected. A low-dose intrarenal infusion of the ₁-adrenoceptor agonist methoxamine (which did not change total RBF or GFR) induced a similar shift as CCO (n=5, RBF: +31±11 mmHg, P<0.05; GFR: +24±4 mmHg, P<0.01). In another group it was shown, that a combination of CCO with an intrarenal angiotensin II (A II) blockade (saralasin) did not significantly alter the response to CCO (n=7). These data suggest an ₁-adrenergic pathway for the sympathetic resetting of autoregulation. An augmented A II formation does not play a major role in mediating this effect.     

Sympathetic a-adrenergic control of large-bore arterial vessels,arterioles and veins,and of capillary pressure and fluid exchange in whole-organ cat skeletal muscle

The sympathetic nervous control of the vascular bed of cat gastrocnemius muscle was studied with a new whole-organ technique which permits simultaneous, continuous and quantitative measurements of capillary pressure (P_c), capillary fluid exchange and resistance reactions in the whole vascular bed and in its three consecutive sections: large-bore arterial vessels (> 25 μm), arterioles (< 25 μm) and veins. The results demonstrated a distinct neural control of all three consecutive vascular sections, graded in relation to the rate of nerve excitation up to maximum at 16 Hz. Stimulation at high rates, which in the steady state caused an average rise of overall regional resistance from 15.3 to 120 PRU (7.8-fold increase), thus raised large-bore arterial vessel resistance from 8.8 to 64 PRU (7.3-fold increase), arteriolar resistance from 4.5 to 49 PRU (10.9-fold increase) and venous resistance from 2.0 to 7 PRU (3.5-fold increase). The rate of resistance development (PRU s^-1) of the sympathetic constrictor response was much higher in the arteriolar than in the other sections, which indicates that the neural control is especially prompt and efficient in the arterioles. A passive component was shown to contribute to the described responses only on the venous side, but in no case by more than 10% of the total sympathetic venous resistance response, which thus is mainly active. Of special functional importance was that the new technique provided information about the adrenergic control of P_c, in absolute figures. From the control value of 19 mmHg, graded sympathetic stimulation caused a graded decline in P_c, at maximum constriction by about 7 mmHg. This resulted in marked net transcapillary fluid absorption, in turn increasing plasma volume.