Flow-driven Diameter Response in Rat Femoral Arteries Perfused In Vitro

The effects of flow and flow changes on arterial diameter were investigated in vitro on isolated rat femoral arteries. Segments of femoral arteries were excised, mounted on microcannulas, and perfused with Tyrode's solution (37°C). Perfusion pressure was kept constant at 90 mm Hg. The mean external diameter after equilibration at a transmural pressure of 90 mm Hg was 720 ± 50 m (n=12). Vessels were then constricted with norepinephrine (1 M in the superfusion solution) to 77% ± 13% of the resting diameter; acetylcholine was used to check endothelial function. The external diameter was measured continuously using video microscopy. The arteries were subjected to two different types of flow variations: (a) step changes in flow (increase and decrease, n=6) and (b) low-frequency sinusoidal flow variations (frequencies ranging from 0.002 to 0.1 Hz, n=11). Flow ranged from 0 to 800 l/min (shear stress ranging from 0 to 15 dyn/cm²). All measured vessels constricted as flow increased. Flow steps induced exponential-like contractions (flow increase) or relaxations (flow decrease) with mean characteristic time constants 31 ± 4 and 22 ± 2 s, respectively. Sinusoidal flow oscillations induced sinusoidal diameter oscillations with a time delay. An increase in the frequency of the flow led to a decrease of both the amplitude of the flow-induced diameter oscillations and the phase shift between flow and diameter. The dynamic diameter response to flow changes could be characterized by a first-order low-pass filter with a time constant of 22 s. © 1998 Biomedical Engineering Society. PAC98: 8745Hw     

Renal hemodynamics and natriuresis during water immersion in normal humans

The renal vascular and functional responses to acute central hypervolemia by water immersion to the neck were determined in six normal subjects. During isotonic-isooncotic expansion by water immersion there was a significant increase in urine flow from 1.1±0.1 to 6.9±1.0 ml/min (p<0.05) and sodium excretion from 99.1±8.8 to 300±28 Eq/min (p<0.05). Glomerular filtration rate did not change while renal blood flow significantly increased during water immersion. Deep intrarenal venous pressure (IRVP) increased from 18.2±1.4 to 32±1.7 mmHg (p<0.05) while mean arterial pressure was unchanged. This marked natriuresis seen during water immersion was associated with reduced renal vascular resistance and increased deep intrarenal venous pressure demonstrating that continued natriuresis could relate to increased capillary hydrostatic pressure.     

Peripheral Chemoreflex and Baroreflex Interactions in Cardiovascular Regulation in Humans

We tested the hypothesis that activation of peripheral chemoreceptors with acute isocapnic hypoxia resets arterial baroreflex control of both heart rate and sympathetic vasoconstrictor outflow to higher pressures, resulting in increased heart rate and muscle sympathetic nerve activity without changes in baroreflex sensitivity. We further hypothesized that this resetting would not occur during isocapnic hyperpnoea at the same breathing rate and depth as during isocapnic hypoxia. In 12 healthy, non-smoking, normotensive subjects (6 women, 6 men, 19-36 years), we assessed baroreflex control of heart rate and muscle sympathetic nerve activity using the modified Oxford technique during normoxia, isocapnic hyperpnoea, and isocapnic hypoxia (85 % arterial O₂ saturation). While isocapnic hyperpnoea did not alter heart rate, arterial pressure, or sympathetic outflow, hypoxia increased heart rate from 61.9 ± 1.8 to 74.7 ± 2.7 beats min⁻¹ (   P < 0.05  ), increased mean arterial pressure from 97.4 ± 2.0 to 103.9 ± 3.3 mmHg (   P < 0.05  ), and increased sympathetic activity 22 ± 13 % relative to normoxia and 72 ± 21 % (   P < 0.05  ) relative to hyperpnoea alone. The sensitivity for baroreflex control of both heart rate and sympathetic activity was not altered by either hypoxia or hyperpnoea. Thus, it appears that acute activation of peripheral chemoreceptors with isocapnic hypoxia resets baroreflex control of both heart rate and sympathetic activity to higher pressures without changes in baroreflex sensitivity. Furthermore, these effects appear largely independent of breathing rate and tidal volume.     

Micropuncture studies of the renal effects of atrial natriuretic substance

Micropuncture studies of the renal effects of atrial natriuretic substance. Injection of atrial extract produced by homogenization, boiling and centrifugation of atrial tissue from one heart caused a 10 fold increase in urine flow rate and a 30-fold increase in Na excretion. Similarly prepared extracts of ventricle were without effect. To identify the site of action of atrial natriuretic substance, extract was infused intravenously at rates corresponding to 3 or 6 atria per hour. During infusion at a rate of 3 atria per hour mean urine flow increased from 9.5±2.8 to 17.2±1.2 l/min and Na excretion from 0.14±0.06 to 1.78±0.14 mol/min. Glomerular filtration rate (GFR), single nephron filtration rate (SNGFR) and proximal and loop of Henle fluid absorption did not change significantly. During infusion of 6 atria per hour, paralleling a greater rise in urine flow rate (from 6.4±2.09 to 40.3±7.5 l/min) and in sodium excretion (from 0.18±0.0008 to 5.97±0.93 mol/min), filtration rate, measured for either the single nephron or the whole kidney, rose. As a consequence of the rise in GFR, delivery of fluid and chloride into the distal tubule increased significantly. These data suggest that to a major extent the natriuresis is caused by transport inhibition along collecting tubules and collecting ducts. In addition, at high doses a rise in filtration rate contributes to the natriuretic effect of atrial extracts.     

Guanylate-cyclase-mediated inhibition of cardiac I Ca by carbachol and sodium nitroprusside

We studied the role of cyclic guanosine monophosphate (cGMP) as a mediator of the reduction of L-type calcium current (I _Ca) induced by muscarinic receptor stimulation and by nitric oxide in isolated guinea-pig ventricular cells using the whole-cell patchclamp technique. Our results show that when the level of cyclic adenosine monophosphate was increased by the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX), stimulation of a pertussis-toxin (PTX)-sensitive muscarinic receptor by carbachol (1 M) reduced the calcium current increase from 80.6±23.5% to 19.8±9.6% over the control and this effect was prevented by methylene blue (10 M), an inhibitor of the soluble guanylate cyclase. Pipette solution containing 10 M cGMP reduced the enhancement of I _Ca by IBMX from 121.9±11.6% to 14.2±5.4% above the control. Sodium nitroprusside (10 M), a spontaneous donor of nitric oxide, and consequently a stimulator of soluble guanylate cyclase, also reduced IBMX-stimulated I _Ca from 115.2±13.2% to 32.2±6.9% above control and the sodium nitroprusside effect was also suppressed by methylene blue. The latter two reagents were ineffective on basal I _Ca.     

The distensibility of mesenteric venous microvessels

Summary In 20 experiments the distensibility characteristics of venous microvessels of 22–148 m internal diameter in response to arterial and venous pressure changes were examined microphotographically in the isolated and perfused mesentery of the dog. Over a range of arterial pressure between 0 and 170 mm Hg venular diameter changed by 31,8±8,8% and venular length by 6.3±4.4%. Venular length changes were significantly correlated to corresponding changes in the accompanying arterioles, whereas no correlation could be found between changes of length and diameter and the control diameters. With venous pressure elevation from 0 to 30 mm Hg an increase of the volume of venous microvessels of about 360% was measured; beyond a venous pressure of 30 mm Hg a limitation of distensibility was observed in these vessels. The moduli of volume elasticity calculated from these data were lower than the moduli reported for the total venous vasculature of the intestinal bed in the range of physiological pressures. It is concluded that the venous microvessels represent the most distensible elements of the venous vascular system.     

Arterial pressure elevation in response to inhibitors of protein synthesis

Summary Antibiotics which inhibit mammalian protein synthesis at different levels were administered intravenously to anesthetized, adrenergic -receptor blocked rats. 60 sec after cycloheximide application (2.5, 5, 12.5 and 25 g/100 g body wt), mean arterial pressure increased an average of 4, 19, 25 and 31% respectively. Mean arterial pressure returned to control values after time lapses varying between 5 and 30 min when maximally effective doses were applied. Neither pressure amplitude nor heart rate were significantly altered. Since blood flow measured in a shunt implanted in the lower aorta also did not change, the pressure response to cyclo-heximide is ascribed to an increase in peripheral vascular resistance.The pressor response to cycloheximide could be related to blockade of protein synthesis as puromycin (2.5 mg/100 g body wt), another inhibitor of translation, induced a similar increase of arterial pressure. Actinomycin D (30 g/100 g body wt) which interferes with RNA synthesis had no acute effect on arterial pressure. Furthermore, the acute effect of cycloheximide is reduced after pretreatment with either actinomycin D, puromycin or cycloheximide.Magnesium deprivation potentiates arterial pressure elevation by cycloheximide and dexamethasone depresses this potentiation. It is postulated that inhibition of protein synthesis at the translation level increases the uptake of contraction triggering calcium by vascular smooth muscle.Part of this work appears in abstract form in Proc. Fifth International Congress of Nephrology, 1972.     

Responses of cat dorsal spino-cerebellar tract neurons to sinusoidal stretching of the gastrocnemius muscle

A defined class of cells within the nucleus dorsalis (Clarke's column) receives excitatory input from Ia afferents of mainly one muscle. Action potentials were recorded from axons of these cells (DSCT neurons) which are excited by Ia afferents of the gastrocnemius muscles. We investigated the response to sinusoidal muscle stretch over a wide range of amplitudes (10 m–4 mm) and frequencies (0.1–130 Hz) in the deefferented preparation. The dynamic stretch was superimposed on a moderate static muscle stretch to ensure that the muscle was not slack during the phase of release. The response up to 10 Hz was displayed as PST histograms (cycle histograms) and a sinewave of stretch frequency was fitted to the PST histograms to define amplitude and phase of a response sinewave.At a constant frequency of about 3Hz, the relation between stretch amplitude and response amplitude could well be described by decelerating intensity functions: the hyperbolic or tanh log function and a modified power function (exponent 0.48±0.12). The phase lead of the response sinewave increased with increasing stretch amplitudes of up to 0.5 mm and then decreased.At constant stretch amplitudes of 0.5–2.0 mm the frequency response was investigated. In relation to stretch frequencies between 0.1 and 1 Hz an increase in the response amplitude of 4.4dB was observed and an increase for 13dB/decade between 3 and 10 Hz. At 0.1 Hz the phase of the response sinewave was 48° in advance and increased to a maximum lead of 89° at 6–8Hz. Above 10Hz the positions of the responding action potentials with respect to the stretch cycle were used to define a phase, which was in advance up to 60 Hz but decreased and changed to a phase lag at higher frequencies.If in PST histograms no periods of silence occurred during the phase of stretch release, the mean discharge rate was found to be independent of the sinusoidal stretching. If the pauses were present the mean rate increased with increasing stretch frequencies or amplitudes.     

Calcium sensitivity and unloaded shortening velocity of hypertrophied and non-hypertrophied skinned human atrial fibres

The mechanical properties of myocardium of different animals are modified by a chronic increase in haemodynamic load. In this study differences in calcium sensitivity and maximum unloaded shortening velocity of hypertrophic and non-hypertrophic chemically skinned human atrial fibres are characterized. Investigating right atria of 34 patients, possible correlations are studied between preoperative atrial pressure, degree of hypertrophy (estimated from the muscle fibre diameter), calcium responsiveness (pCa₅₀ eliciting half-maximum contraction) and V _max (unloaded shortening velocity). Hypertrophic fibres from atrial appendages of patients having an increased right atrial pressure (RAP 8.5±1.6 mm Hg) and suffering from mitral valve disease (stenosis and insufficiency combined) had a fibre diameter of 18.0±0.9 m. They also had a higher calcium sensitivity (pCa₅₀ 5.65±0.08) and a lower unloaded shortening velocity (1.7±0.1 muscle lengths/s) than non-hypertrophic fibres from the appendages of patients with normal right atrial pressure (RAP 3.2±0.5 mm Hg) and coronary heart disease (CHD: pCa₅₀ 5.45±0.04; V _max= 3.4±0.2 muscle lengths/s; fibre diameter 12.8±0.4 m). Thus non-hypertrophic fibres from control CHD patients differed significantly (p < 0.01) from hypertrophied atrial fibres of patients with mitral valve disease and with combined valve disease (MAV, pCa₅₀=5.58±0.05, V _max 2.0±0.3 muscle lengths/s, fibre diameter 14.6±0.9 m) or aortic valve disease (stenosis combined with insufficiency, fibre diameter 14.8±1.4 m, pCa₅₀ 5.56±0.03, V _max 2.0±0.24 muscle lengths/s; RAP 11.0±2.6 mm Hg). Such alterations of calcium responsiveness, shortening velocity and fibre thickness may reflect an adaptation to the chronic overload in atria from patients with various forms of heart valve disease.     

Barium ions reduce contraction kinetics in rat tracheal smooth muscle

In isolated rat tracheal smooth muscle, contraction was induced by electrical field stimulation (= EL; frequency = 30 Hz; pulse duration = 0.17 ms), 10 mol/l acetylcholine (= ACh), potassium depolarization (137 mmol/l K), or by 10 mmol/l barium (= BA). Contraction kinetics were studied by analyzing tension recovery after cessation of a 1.8s length vibration (100 Hz sinusoida; amplitude = 6% of the muscle length). The contraction speed was high during EL as can be seen from the short time constant of post-vibration tension recovery (=5.90±0.14 s) found 30 s after onset of stimulation. The time constants of tension recovery during long-term (50 min) activation averaged 12.88±0.32 s (K) and 13.24±0.17 s (ACh) when the vibration was stopped 8–45 min after onset of activation. As both of these stimuli act mainly via cholinergic receptors, similar down-regulated contraction kinetics occur under steady-state conditions of tonic contraction. However, during barium activation steady-state conditions need a 45 min agonist incubation, and the time constant of post-vibration tension recovery was extended to 34.05±2.21 s. Thus, calcium may be replaced by barium in the force generation process but it produces slower cycling of cross-bridges.     

Spike conduction properties of T-shaped C neurons in the rabbit nodose ganglion

Noradrenaline (NA) and angiotensin II (A II) were infused intravenously in conscious dogs without (series I) and with (series II) additional infusions of sodium nitroprusside at doses re-establishing normal levels of mean arterial pressure (MAP). In series I, NA infusion (1.6 g/min per kg for 30 min) initially elevated MAP by some 25 mm Hg and lowered heart rate by some 30 beats/min. Plasma concentrations of arginine vasopressin (AVP) remained constant, while those of A II and atrial natriuretic factor were slightly, but significantly, increased. Infusion of A II (10 or 20 ng/min per kg for 30 min) induced similar rises in MAP and slight reductions of heart rate and increased plasma AVP by 70% and atrial natriuretic factor by 60%. In series II, sodium nitroprusside (1–4 g/min per kg) was added for 30 min to infusions of NE (1.6 g/min per kg) and A II (20 ng/min per kg) in order to maintain MAP at its control level. This resulted in an 11-fold increase in plasma AVP during NA infusion and a 19-fold increase during A II infusion. Infusing sodium nitroprusside (4 g/min per kg) alone lowered MAP to clearly hypotensive levels, but the resulting rises in plasma AVP were less than, rather than equal to, those seen at normotensive MAP levels during the combined infusions of sodium nitroprusside with A II or NA, respectively. It is concluded that both NA and A II exert strong stimulatory actions on AVP release which are, however, counteracted by inhibitory influences arising from the hypertensive effects of NA and A II.     

Stimulus-specific patterns of myosin light chain phosphorylation in smooth muscle of rabbit thoracic artery

When the rabbit thoracic artery was stimulated with submaximal concentrations of agonist [40 mM K⁺, 30 M prostaglandin F₂ (PGF₂) or 7 M histamine], about 90% of a maximal contraction occurred. Each agonist induced a rapid development of contraction followed by a sustained response. The maximal rate of force generation stimulated with PGF₂ was twice that seen with K⁺ or histamine. Stimulation with 40 mM K⁺ increased the extent of monophosphorylated 20 kDa myosin light chain (MLC-P) for up to 1 min to a maximal value of 38.8±1.0%, there was a subsequent rapid decrease and the MLC-P level remained just above the basal value for 40 min (6.8±3.0%). In the case of stimulation with 7 M histamine, MLC-P level increased rapidly and was sustained for up to 40 min (28.0±4.9%). In contrast to the stimulation with K⁺ or histamine, PGF₂ induced both mono- and diphosphorylated MLC₂₀ (MLC-P and MLC-P 2 respectively) at a low concentration (3 M). The monophosphorylation of MLC₂₀ induced by 30 M PGF₂ reached the maximal value of 32.8±5.2%, and was sustained for up to 40 min (15.2±5.4%). The diphosphorylation of MLC₂₀ increased rapidly (7.4±4.0% at 5 min), then decreased to the basal value within 40 min. These results suggest that different modes of stimulation of smooth muscle contraction produce different profiles of MLC₂₀ phosphorylation. The implications of these observations are that the diphosphorylated form, specifically induced by certain agents, may modify the mode of contraction of the aortic artery.     

The Rate of Protein Digestion affects Protein Gain Differently during Aging in Humans

Dehydration is known to decrease orthostatic tolerance and cause tachycardia, but little is known about the cardiovascular control mechanisms involved. To test the hypothesis that arterial baroreflex sensitivity increases during exercise-induced dehydration, we assessed arterial baroreflex responsiveness in 13 healthy subjects (protocol 1) at baseline (PRE-EX) and 1 h after (EX-DEH) 90 min of exercise to cause dehydration, and after subsequent intravenous rehydration with saline (EX-REH). Six of these subjects were studied a second time (protocol 2) with intravenous saline during exercise to prevent dehydration. We measured heart rate, central venous pressure and arterial pressure during all trials, and muscle sympathetic nerve activity (MSNA) during the post-exercise trials. Baroreflex responses were assessed using sequential boluses of nitroprusside and phenylephrine (modified Oxford technique). After exercise in protocol 1 (EX-DEH), resting blood pressure was decreased and resting heart rate was increased. Cardiac baroreflex gain, assessed as the responsiveness of heart rate or R-R interval to changes in systolic pressure, was diminished in the EX-DEH condition (9.17 ± 1.06 ms mmHg⁻¹ vs. PRE-EX: 18.68 ± 2.22 ms mmHg⁻¹, P < 0.05). Saline infusion after exercise did not alter the increase in HR post-exercise or the decrease in baroreflex gain (EX-REH: 10.20 ± 1.43 ms mmHg⁻¹; P > 0.10 vs. EX-DEH). Saline infusion during exercise (protocol 2) resulted in less of a post-exercise decrease in blood pressure and a smaller change in cardiac baroreflex sensitivity. Saline infusion caused a decrease in MSNA in protocol 1. We conclude that exercise-induced dehydration causes post-exercise changes in the baroreflex control of blood pressure that may contribute to, rather than offset, orthostatic intolerance.     

Re-acceleration of the down-regulated contraction kinetics in the rat tracheal smooth muscle

The contraction kinetics of smooth muscle show a down-regulation after the transient rise found during sustained contraction. We tried to find out therefore if the contraction kinetics of rat tracheal smooth muscle can be re-accelerated during sustained activation. A 2 s length vibration (100 Hz sinusoidal; amplitude=6% of the muscle length) produces an immediate fall in the force developed by the activated muscle. A biexponential function was fitted to the force recovery. The reciprocal of the time constant,t ₂, describing the slow component of force recovery, reflects the kinetics of contraction. The contraction kinetics reach their highest levels (t ₂=4.9±0.1 s,n=166) about 30 s after the onset of electrical field stimulation. Three experimental groups were activated by either 10 M serotonin (5-HT), 100 M acetylcholine (ACh), or by 2 M ACh for 50 min. Approximately 10 vibrations were applied to each preparation after an 8 min activation in order to observe stabilized down-regulated contraction kinetics.t ₂ values were calculated from the force recovery after vibration and averaged 11.2±0.2 s (n=141), 11.5±0.2 s (n=137), and 11.1±0.3 s (n=84), respectively. After 50 min of continuous chemical activation, the preparation was stimulated additionally by the neurogenic release of acetylcholine. Thet ₂ of post-vibration force recovery, as measured after 30 s of neural activation, showed no change in the specimens basically activated by 100 M ACh (11.0±0.4 s,n=51). A decline int ₂, indicating accelerated kinetics, was observed in the groups which had been stimulated by 10 M 5-HT (5.9±0.2 s,n=51) and 2 M ACh (5.6±0.2 s,n=47). The re-accelerating effect of the second stimulus could be reproduced recurrently. The down-regulated contraction kinetics can be re-accelerated either by activating another receptor type in addition to the one already maximally stimulated or by increasing the stimulus mediated by one of the receptor types from half maximal to maximal strength. However, this is only possible if the additional activation is strong enough, as indicated by an increase in active force. It could be demonstrated that the slowing of the cross-bridge cycling rate is the result of a regulatory process and not the result of substrate deficiencies or refractoriness in the regulatory of contractile proteins.     

Plasma histamine and clinical tolerance to infused histamine in normal,atopic and urticarial subjects

Five subjects with a recent history of urticaria (U), five atopic (A) subjects and a non-atopic (NA) control group were given intravenous infusions of histamine starting at 0.05 g/kg/min, increasing by 0.05 g/kg/min every 30 minutes to a maximum of 0.35 g/kg/min. Plasma histamine levels were monitored every 15 minutes. The infusion was stopped when an objective clinical endpoint was reached, involving either evidence of peripheral vasodilatation (rise of skin temperature by at least 1 °C) or a 20% fall of peak expiratory flow rate.There were no significant differences in resting plasma histamine in the three groups. Those with urticaria reached the clinical endpoint at a lower infusion rate than non-atopic subjects (U 0.22±0.02 g/kg/min; A 0.26±0.02 g/kg/min; NA 0.32±0.2 g/kg/min.p<0.008) they also received a lower total histamine dose (U 1.12±0.33 mg; A 1.42±0.38 mg, NA 2.2±0.51 mg,p<0.008). Atopic subjects with a history of asthma, eczema or rhinitis also tolerated histamine poorly, some subjects reaching a clinical endpoint while the plasma histamine level was still relatively low (U 1.52±0.4 ng/ml, A 0.85±0.19 ng/ml, NA 1.4±0.44 ng/ml,p=0.05). After the histamine infusion was stopped, the fall in the blood level of histamine was slower in urticarial subjects than in the other two groups, with a half-life of 6.2±1.3 min (A 3.0±1.2 min, NA 4.0±0.7 min,p<0.02). There were thus differences in the metabolism of histamine in our non-atopic urticarial subjects and increased histamine sensitivity in atopic subjects which require further study.     

Glucose kinetics during prolonged exercise in euglycaemic and hyperglycaemic subjects

To determine the limits to oxidation of exogenous glucose by skeletal muscle, the effects of euglycaemia (plasma glucose 5 mM, ET) and hyperglycaemia (plasma glucose 10 mM, HT) on fuel substrate kinetics were evaluated in 12 trained subjects cycling at 70% of maximal oxygen uptake (VO_{2, max}) for 2 h. During exercise, subjects ingested water labelled with traces of U-¹⁴C-glucose so that the rates of plasma glucose oxidation (R _ox) could be determined from plasma ¹⁴C-glucose and expired ¹⁴CO₂ radioactivities, and respiratory gas exchange. Simultaneously, 2-³H-glucose was infused at a constant rate to estimate rates of endogenous glucose turnover (R _a), while unlabelled glucose (25% dextrose) was infused to maintain plasma glucose concentration at either 5 or 10 mM. During ET, endogenous liver glucose R _a (total R _a minus the rate of infusion) declined from 22.4±4.9 to 6.5±1.4 mol/min per kg fat-free mass [FFM] (P<0.05) and during HT it was completely suppressed. In contrast, R _ox increased to 152±21 and 61±10 mol/min per kg FFM at the end of HT and ET respectively (P<0.05). HT (i. e., plasma glucose 10 mM) and hyperinsulinaemia (24.5±0.9 U/ml) also increased total carbohydrate oxidation from 203±7 (ET) to 310±3 mol/min per kg FFM (P<0.0001) and suppressed fat oxidation from 51±3 (ET) to 18±2 mol/min per kg FFM (P<0.0001). As the rates of oxidation at more physiological euglycaemic concentrations of glucose were limited to 92±9 mol/ min per kg FFM, and were similar to those reported when carbohydrate is ingested, the results of the current study suggest that the concentrations of glucose and insulin normally present during prolonged, intense exercise may limit the rate of muscle glucose uptake and oxidation.     

Baroreflex sympathetic activation increases threshold pressure for the pressure-dependent renin release in conscious dogs

Stimulus-response curves relating renal-venous-arterial plasma renin activity difference (P.R.A.-difference) to mean renal artery pressure (R.A.P.) were studied in seven chronically instrumented conscious foxhounds with a daily sodium intake of 6.1 mmol/kg. R.A.P. was reduced in steps and maintained constant for 5 min using an inflatable renal artery cuff and a pressure control system.The stimulus-response curve obtained during control conditions (C) or during common carotid artery occlusion (C.C.O.) could be approximated by two linear sections: a rather flat section or plateau-level of P.R.A.-difference at normal blood pressure or above, and a very steep section between a distinct threshold pressure and 65–70 mm Hg. While the parameters of the curves varied from dog to dog, the curves kept their inique shape in the individual dog for at least 1 week. C.C.O. had no effect on the plateau-level of the P.R.A.-difference (C:0.98±0.14,C.C.O.:0.99±0.14 ng Al·ml^–1·h^–1) and on the slope of the curve below threshold pressure (C:–0.379±0.041,C.C.O: –0.416±0.082 ng Al·ml^–1·h^–1·mm Hg^–1) but shifted the stimulus-response curve to the right and increased threshold pressure (C:92.7±2.8,C.C.O.:109.7±4.1 mm Hg;P<0.05).Renal blood flow, which was measured simultaneously in three of the dogs, showed good autoregulation down to 70 mm Hg under resting conditions and was not affected by C.C.O. except for a 30% reduction of renal blood flow at the lowest pressure step (70 mm Hg).-Adrenergic blockade in 4 of the dogs reduced the plateau-level of the P.R.A.-difference from 0.86±0.19 to 0.36±0.05 ng AI·ml^–1·h^–1 (P<0.05) but had no effect on the increase of threshold pressure elicited by C.C.O.It is concluded that the stimulus-response curve for the pressure-dependent renin release has a remarkable long-term stability in the individual dog. The curve is shifted to the right by a moderate carotid baroreflex increase of renal sympathetic nerve discharge which leaves total renal blood flow largely unchanged. It is suggested that the increase in threshold pressure is independent of -adrenergic effects.This study was supported by the German Research Foundation within the SFB 90, HeidelbergA priliminary part of this investigation has been presented to the meeting of the German Physiological Society, Dortmund, March 1984 [Pflügers Arch (1984) suppl 400:R11,41]     

Disparate effects of calcium channel blockers on pressure dependence of renin secretion and flow in the isolated perfused rat kidney

Using the model of isolated perfused rat kidneys this study was performed to investigate whether or not voltage-operated calcium channels are essentially involved in the pressure control of renin secretion from the kidneys. At a perfusion pressure of 100 mm Hg (13.3 kPa) renin secretory rates were 4.2±0.7 (ng angiotensin I h^–1) min^–1 g^–1. Stepwise reduction of renal perfusion pressure to 80, 60, and 40 mm Hg (10.6, 8.0, 5.3 kPa) resulted in an increase of renin release yielding a 30-fold stimulation at 40 mm Hg vs 100 mm Hg. Increasing the perfusion pressure above 100 mm Hg did not further significantly decrease renin secretion. The perfusate flow rate was also pressure-dependent. Flow rates increased linearly with pressure and reached a plateau at 100 mm Hg, which was maintained up to 160 mm Hg (21.3 kPa). The averaged flow rate at the plateau was 15.5 ml min^–1 g^–1. In the presence of the three different calcium antagonists nifedipine (5 M), nitrendipine (3 M) and verapamil (5 M), myogenic autoregulation of flow was abolished as indicated by the rise of the pressure/flow curve between 40 and 160 mm Hg. At the same time, however, these calcium channel blockers did not alter the relationship between perfusion pressure and renin secretion. Moreover, the calcium channel agonist Bay K 8644 (5 M) caused a strong and long-lasting vasoconstriction, without changing renin secretion. Taken together, our findings indicate that organic calcium antagonists at concentrations sufficient to block voltage-operated calcium channels in vascular smooth muscle cells have no influence on the pressure-dependent control of renin secretion. In consequence, it appears unlikely that voltage-operated calcium channels are essentially involved in the signal transduction mechanism that links renin secretion and blood pressure.     

Effect of posture on arterial baroreflex control of heart rate in humans

Summary Altered baroreflex function may contribute to the cardiovascular changes associated with weightlessness. Since central blood volume (CBV) increases during simulated weightlessness, we have examined the possibility that acute changes in CBV may modify baroreceptor function. We used graded head-up tilt (HUT) and head-down tilt (HDT) to induce changes in CBV, and neck suction to stimulte carotid baroreceptors, in 6 subjects. The increase in pulse interval induced by a negative pressure of 8.2 kPa (62 mm Hg) imposed for 10 s while supine was compared with the increase while tilted for 8 min at ± 15, ± 30 and ± 45. During HDT at 15 the pulse interval over the first 5 cardiac cycles following suction onset was 51 ± (SEM) 18 ms longer (p<0.05), at 30 it was 61±20 ms longer (p<0.05), and at 45 it was 74±35 ms longer (p<0.01), compared with supine. During HUT at 15 the pulse interval was 25±9 ms shorter (p<0.05) than when supine, but was not significantly different at 30 and 45. These responses occurred independently of changes in brachial blood pressure. Attenuation was also observed after 5 min (56±17 ms; <0.05), and after 40 min (25±9 ms; p<0.05) of 60 HUT compared with supine. We conclude that posture does modify arterial baroreflex control of heart rate. If this occurs primarily as a result of a change in CBV, then the acute effect of weightlessness may be an accentuation, not an attenuation, of baroreflex function.M. H. Harrison was a National Research Council postdoctoral research fellow on leave from the Ministry of Defence, UK     

Time-dependent effect of sectioning carotid sinus nerves on the vagally mediated baroreflex

The purpose of the reported experiments was to examine whether the vagally mediated baroreflex system (V-system) increases its feedback gain with time after sectioning of the carotid sinus nerves (CSN). In 10 dogs anesthetized with Nembutal, we determined the overall open-loop gain (G) of the rapidly acting arterial pressure control system. G was assessed as (AP_I/AP_S)-1, where AP_I and AP_S represent the immediate and steady-state decreases in arterial pressure at the aortic arch following a fast step-wise reduction in blood volume. AP_I, AP_S and G_INTACT in the intact condition (30th min before sectioning of the CSN) were –1.8±0.1 kPa, –0.20±0.01 kPa and 8.4±0.3 (mean±SE), respectively. The mean values of AP_I, AP_S and G after sectioning of the CSN (G_V), first averaged within individual dogs and then averaged for ten dogs, were –2.53±0.07 kPa, –1.1±0.05 kPa, and 1.5±0.1, respectively. G_V did not change with time over about 4 h after sectioning of the CSN. It is concluded that the V-system cannot augment its ability to restore arterial pressure in compensation for the lost function of the carotid sinus baroreflex system over 4 h after sectioning of the CSN in the anesthetized dog.