The role of the cardiac nerves in the regulation of sodium excretion in conscious dogs

Conscious, chronically instrumented dogs, maintained on a high sodium intake, were used to investigate whether surgical cardiac denervation impairs the natriuresis associated with left atrial pressure increase produced in three ways: during an increase in left atrial pressure by means of a reversible mitral stenosis (protocol 1); after an i.v. saline load (1.0 ml 0.9%·saline min^–1·kg^–1 over 60 min) (protocol 2); after an oral saline load (14.5 mmol Na·kg^–1 given with the food as an isotonic solution) (protocol 3).During a reversible mitral stenosis, in intact dogs, urine volume and sodium excretion increased markedly (from 34–145 l·min^–1·kg^–1 and from 3–12 mol·min^–1·kg^–1); mean arterial pressure increased by an average of 2 kPa (15 mm Hg) and heart rate by 55 b/min; plasma renin activity fell from 0.37–0.21 ng Al·ml^–1·h^–1. Cardiac denervation eliminated these effects of left atrial distension except for a small increase in heart rate (12 b/min). This indicates that the natriuresis and diuresis during left atrial distension resulted from stimulation of receptors located in the left atrium.In contrast, during protocol 2 and 3, the same amounts of sodium and water were excreted in the cardiac denervated dogs as compared to the intact dogs. A comparable decrease in plasma renin activity also was observed. — Apparently the presence of the cardiac nerves is not a prerequisite for maintenance of sodium and water homeostasis.     

No relation between atrial natriuresis and renal blood flow in conscious dogs

Summary Conscious dogs were used to study whether changes in total renal hemodynamics are responsible for diuresis and natriuresis during an experimental increase in left atrial pressure (LAP). To ensure a controlled dietary sodium intake, the dogs (n=8) were chronically kept on ahigh or alow sodium intake diet (HSI; LSI). After the dogs had completely recovered from surgery (carotid loop, thoracotomy, flank incision), LAP was increased by about 10 cm H₂O for 60 min by tightening a purse string around the mitral annulus (51 expts). Mean urine volume (V) increased in both groups to a comparable degree. Mean sodium excretion increased somewhat more in HSI dogs, but remained elevated in LSI dogs after the LAP increase. Renal blood flow (electromagnetic flow transducer) and inulin clearance did not change. Renal vascular resistance (RVR) increased by about 20% (HSI) and 15% (LSI). — When the induced LAP increase was terminated, V decreased. RVR decreased in HSI dogs by about –11% and in LSI dogs by about –6% below control values.—It is concluded that volume regulatory mechanisms induced by an experimental LAP increase operate independently of changes in total renal blood flow.The Arbeitsgruppe Experimentelle Anästhesie is member of the Research Group Autonomic Regulations Freie Universität Berlin     

Left atrial pressure and postprandial diuresis in conscious dogs on a high sodium intake

Summary 5 conscious, well trained, female dogs kept on a high sodium intake (14 meq Na/kg bw) were used to measureeft atrial pressure (LAP), urine volume ( ), sodium and potassium excretion (U_Na , U_K ) as well as plasma osmolality (P_osm) before and up to 180 minafter food intake. The dogs were fitted with a catheter in the left atrium (thoracotomy). In all experiments (n=23) LAP increased postprandially (pp) above fasting controls. The mean peak increase range from 4 to 6 cm H₂O and was observed as early as 61–80 and as late, as 161–180 min pp. Increase in LAP was closely correlated to V which rose from 36±28 to 160±51 ul/min·kg. pp was also correlated to pp U_Na which increased from 4.8±3.3 to 34.0±8.5 ueq/min·kg.The pp increase in LAP and its close relation to pp and pp U_Na emphasize the assumption that intrathoracic receptors are involved in the regulation of body fluids.     

Reduction of renal nerve activity by volume expansion in conscious cats

Summary In conscious cats with intact or denervated baroreceptors volume expansion of 5–15% of blood volume was, performed with dextran and isotonic sodium chloride. Renal sympathetic activity (RSA), electroencephalogram (EEG) blood pressure (BP) and heart rate (HR) were recorded. RSA was reduced by 25–85% in 10 experiments out of 11 by volume expansion both with dextran and isotonic sodium chloride. Reduction of RSA could not be related to different states of wakefulness as indicated by the EFG, so could only be caused by volume expansion, although no quantitative correlation could be detected. No differences were observed between animals with intact and denervated baroreceptors. In most experiments BP and HR decreased during volume expansion up to –25 mm Hg and up to –23 beats/min, respectively. The degree of BP and HR reduction could not be related to the degree of RSA reduction. The results suggest that changes in RSA might be involvec in the renal response to volume expansion.Supported by the Deutsche Forschungsgemeinschaft.     

The influence of long-term infusion of the calcium antagonist diltiazem on postischemic acute renal failure in conscious dogs

Summary The influence of long-term infusion of the calcium-entry blocker diltiazem on postischemic acute renal failure was investigated in conscious dogs monitored by implanted instruments. In 18 uninephrectomized beagle dogs on a salt-rich diet, an electromagnetic flow probe and an inflatable plastic cuff were placed around the renal artery. Acute renal failure was induced by inflating the cuff for 180 min in the conscious animal. Group A (n=5, control) received an intraaortic injection of 0.9% NaCl (5 ml/day) from the 3rd day before until the 7th day after ischemia and group B (n=6, posttreatment) an intra-aortic injection of diltizem (5 µg·min^–1·kg^–1) beginning at the end of ischemia until the 7th day. Group C (n=7, pre- and posttreatment) received diltiazem from the 3rd day before until the 7th day after ischemia. In group A, renal blood flow dropped from 149±16 (preischemic) to 129±29 ml·min^–1 on the 1st day after ischemia. In contrast, renal blood flow increased on the 1st postischemic day in both treatment groups by 29±15% (group B,P 0.05) and 14±13% (group C). In the following days, there was no significant difference in renal blood flow between groups A, B and C. In group B, the reduction of the glomerular filtration rate was similar to that in the control group. In group C, the glomerular filtration rate was significantly less reduced than in group A (34±1.8 preischemically to 17±5.4 on day 1,P 0.05 and 20±4.1 ml·min^–1 on day 7,P 0.05). Plasma renin activity increased in both diltiazem groups, more pronounced so in group B (from 3.7±1.0 on day 1 to 16.2±7.9 ng ATI·ml^–1·h^–1 on day 7,P 0.05). In contrast to groups A and B, the increase in fractional sodium excretion was less pronounced in group C. Likewise, the decrease in free water-reabsorption was less marked than in groups A or B. It was apparent that diltiazem, when administered pre- and post-ischemically, preserved glomerular filtration rate and renal blood flow. When diltizem was given solely postischemically there was an improvement in renal blood flow, but no significant influence on glomerular filtration rate. We therefore conclude that mainly tubular factors, in addition to the attenuation of postischemic vasoconstriction, are involved in the protective effect of diltiazem on postischemic acute renal failure in conscious dogs.Abbreviations ARF acute renal failure - C_osmol clearance of osmolarity - E_Na urinary excretion rate of sodium - FE_Na fractional excretion rate of sodium - GFR glomerular filtration rate - HR heart rate - NE norepinephrine - PAM mean arterial blood pressure - PRA plasma renin activity - RBF renal blood flow - RVR renal vascular resistance - T_H2_O free water reabsorption - V_U urine volume     

Effects of bilateral carotid occlusion and auditory stimulation on renal blood flow and sympathetic nerve activity in the conscious dog

In conscious foxhounds with intact aortic baroreceptors the effects of common carotid occlusion (C. C. O.; 3 dogs) or excitement (elicited by a sudden loud noise due to firing a pistol; 7 dogs) on renal blood flow (R.B.F.) were studied. C.C.O. increased arterial blood pressure by 40–50 mm Hg and heart rate by 22 beats/min while R.B.F. remained unchanged. When kidney perfusion pressure was maintained during C.C.O. there was also no change in R.B.F. Excitement increased mean aortic blood pressure by 35 mm Hg and heart rate by 84 beats/min; R.B.F. was transiently reduced by 40% of control.In another 3 foxhounds successful recordings of renal sympathetic nerve activity (R.S.N.A.) were obtained in the conscious state for 2–7 postoperative days. The effects of C.C.O. or excitement — elicited by whistling or hand-clapping — on R.S.N.A. were tested. There was pulse-synchronous nerve activity in the resting conscious animal. C.C.O. induced a steady state increase of averaged R.S.N.A. by 62% of control. Excitement was associated with transient bursts of activation of averaged R.S.N.A. by 500% of control.It is concluded that total R.B.F. is not changed during the baroreceptor short-term adjustment of blood pressure although changes in sympathetic outflow to the kidney are observed under comparable conditions. In contrast, excitement causes a much higher degree of sympathetic activation; this is probably responsible for the intense, transient renal vasoconstriction.This study was supported by the German Research Foundation within the S.F.B. 90 Heidelberg     

Atrial natriuresis under the condition of a constant renal perfusion pressure

An experimental elevation of left atrial pressure (eLAP ) by means of a reversible mitral stenosis is accompanied with an increase in sodium excretion (UNa—) and arterial blood pressure (by about 20 mm Hg, 2.7 kPa), and by a decrease in plasma renin activity.It is well established that an increase in renal perfusion pressure (Pren) can augment UNa—. Therefore the present study was undertaken to examine whether the eLAP -induced natriuresis was caused by the increased Pren. — Four female beagle dogs were kept under controlled environmental conditions. They received asodium rich diet (14.5 mmol/Na/kg/d). The dogs were chronically instrumented: purse string around the mitral annulus, catheter in the left atrium, carotid loop, pneumatic cuff above the renal arteries, pressure transducer below the renal arteries. Pren was kept constant by means of a digital servofeedback control circuit. The dogs served as their own controls (13 experiments without and 15 experiments with a controlled renal perfusion pressure were performed).After eLAP(+1.0 kPa), UNa— rose from 4.1±2.6 to 10.3±3.9 mol Na/min/kg. If Pren was kept constant, the corresponding values were 4.2±2.8 and 9.3±2.9 mol/min/kg. These data clearly indicate that the atrial natriuresis is not mediated by an augmentation of renal perfusion pressure. Therefore these results support the hypothesis that atrial natriuresis probably is due to an eLAP-induced suppression of the renin-angiotensin-system or other natriuretic mechanisms.Abbreviations ADP 3×20 min After distension period - AN Atrial natriuresis - bw kg Body weight - CP 3×20 min Control period - DP 3×20 min Distension period - eLAP kPa Experimental increase of left atrial pressure (during all DP's about +1.0 kPa) - HR l/min Heart rate - LAP kPa Left atrial pressure - n ₁ Number of dogs used - n ₂ Number of experiments (1 expt/day) - n ₃ Number of collection periods (urine) or number of samples (HR) - Part kPa Mean systemic arterial blood pressure (carotid artery) - Pren kPa Mean renal perfusion pressure (aorta, below the renal arteries) - UCI— mol/min/kg Chloride excretion - UK— mol/min/kg Potassium excretion - UNa— mol/min/kg Sodium excretion - Uosm— osm/min/kg Osmolar excretion - — l/min/kg Urine volume Preliminary parts of this work have been presented in Kiel (Spring meeting of the Deutsche Physiologische Gesellschaft, March 1979) and in Stockholm, Sweden (III. European Colloquium on Renal Physiology, June 1979).     

Left atrial pressure and sodium balance in conscious dogs on a low sodium intake

Summary 10 conscious chronically prepared dogs were used. After recovery from thoracotomy (catheter into the left atrium, nylon purse string around the mitral annulus) they were kept chronically on a low sodium intake (<0.5 meq Na/kg bw daily). On 51 days left atrial pressure (LAP) was increased for 60 min about 10 cm H₂O once daily by tightening the purse string (distension period: DP).During DP urine volume ( ) increased about threefold, and sodium excretion (E _Na) about sixfold. The amount of renal sodium loss on the days when LAP was increased exceeded the daily intake considerably. The application of DOCA (15 mg i.m.) did not diminishE _Na during DP and 60 min thereafter. During DP heart rate increased by about 70 b/min and mean arterial blood pressure increased by about 15 mm Hg.The data suggest that stimulation of intrathoracic receptors by a reversible mitral stenosis augments renal sodium excretion even in a state of a highly stimulated tubular sodium resorption.Preliminary reports of parts of this work have been presented at the meetings of the Deutsche Physiologische Gesellschaft in Bochum (1975) and Wien (1975). The authors are indebted to Dr. Üdes and Dr. Nebendahl for the invaluable veterinary assistance and to Mrs. Jäckel and Mrs. Mohr for technical assistance. Dr. Eisele is surgeon at the Schloßparkklinik, BerlinThe AG Experimentelle Anaesthesie is member of the Research Group Autonomic Regulations, FU Berlin     

Thoracic duct lymph in conscious dogs at rest and during changes of physical activity

Summary In conscious dogs with a thoracic ductvenous shunt, lymph flow (LF), protein concentration (LP), transported protein (LTP), albumin concentration (LA), globulin concentration (LG), albumin to globulin ratio (LAG), plasma disappearance rate of labelled albumin (k), plasma volume (PV) and intravascular protein pool (IVP) were studied at rest, during walking and muscle relaxation induced by guajacolglycerinether.At rest, LF approximated 50 l/min · kg and LTP 1.55 mg/min · kg. LF and LTP correlated positively with the state of physical activity. LP was 54%, LA 67%, LG 43%, but LAG 156% of the plasma values; k was 0.00228.Relaxation reduced LF by 34%, LTP by 31%, LAG by 7% and the lymph concentration of i.m. applied labelled albumin by 54%. PV, IVP and k were not changed significantly.Walking enhanced LF by 100%, LTP by 50% and LAG by 25%. LP was decreased by 15%. PV, IVP and k were not changed significantly.Control data suggest a significant influence of anaesthesia on thoracic duct lymph flow, composition and protein transport. Spontaneous and experimental changes of thoracic duct lymph may be explained by changes of the activity of the tissue pump. An extravascular fluid and protein pool would seem to be accumulated at rest and emptied during exercise.Supported by the Deutsche ForschungsgemeinschaftParts of this study were presented at the 44th meeting of the Deutsche Physiologische Gesellschaft [24]     

Quantitative and sustained suppression of renal sympathetic nerve activity by left atrial distension in conscious dogs

In order to investigate the interrelations between left atrial pressure (Pla) and renal sympathetic nerve activity (RSNA) and heart rate (HR), Pla was increased by a balloon both in conscious sham-operated and cardiac-denervated dogs. RSNA was decreased and HR was increased with increasing Pla in sham-operated dogs. The reflex changes in RSNA and HR induced by the stimulation of atrial receptors persisted for at least 15 min. There was a consistent relationship between Pla and RSNA which could be described by a single exponential equation: % RSNA = 80.0(1–e^{–0.395 Pla}), or by a linear equation when Pla was less than 6 mmHg; %RSNA=-13.5Pla–2.25. The relationship between Pla and HR can be described by a single exponential equation: HR = 86.5(1–e^{–0.125 Pla}). A significant linear relationship between RSNA and HR was obtained during a graded left atrial distention (%RSNA=-1.08HR–17.7). In cardiac-denervated dogs, RSNA tended to increase and HR remained constant during the left atrial distention. These results indicate that left atrial receptors regulate RSNA and HR in both a quantitative and sustained manner in conscious sham-operated dogs.     

Influence of renal nerves on renin secretion in the conscious dog

In order to evaluate the influence of renal nerves on renin secretion during changes in blood volume, we studied the mean arterial blood pressure (MAP) and the renal venous plasma renin activity (PRA) in 6 conscious dogs having one intact and one denervated kidney.After a passive head-up tilt PRA increased significantly in the vein of the intact kidney while it remained stable in the denervated one.The intravenous injection of Furosemide (3 mg/kg) induced a rapid elevation of PRA in both renal veins. The kinetics of the variations of renin secretion were similar in the two kidneys, but its magnitude was significantly lower in the denervated side.After a slow hemorrhage of 2, 4 and 6 ml/kg, MAP was unchanged and PRA increased in both renal veins but in a significantly lower degree in the denervated side. When blood loss reached 8 ml/kg, MAP decreased and PRA increased identically in the two renal veins.It was concluded that, in conscious dogs, the renal nerves could participate in the rapid adaptations of renin secretion during small changes in the circulating blood volume.     

Renal hemodynamics and proteinuria in running and swimming beagle dogs

Summary In beagle dogs swimming, in contrast to treadmill running, was found to cause an increase in urine flow and urinary protein excretion. Renal blood flow measured by electromagnetic flow probes decreased by 13.0±4.9% when the treadmill gradient was 15% and arterial pressure was elevated by 11.6±4.9%. Immersion resulted in an immediate decrease in renal blood flow of 8.8±5.1% and a 24.6±6.9% increase in arterial pressure. Acid-base status indicated a respiratory alkalosis in all running experiments, no net change in five swimming experiments in which hyperventilation occured, but a metabolic acidosis in eight swimming experiments without hyperventilation. During running there was a threefold increase in oxygen consumption. We conclude that swimming possibly induces more sympathetic nervous activity than treadmill running in dogs, while an alkalosis is consistently present during running, but acid-base response is variable during swimming.     

Changes of collateral perfusion pressure and segmental coronary resistances during reactive hyperemia in anesthetized dogs

Changes of collateral perfusion pressure (CPP) and segmental coronary resistances during reactive hyperemia were studied in nine chloralose-urethan-morphine anesthetized open-chest dogs. Coronary perfusion pressure was controlled by a cannula in the left main coronary artery and inflow measured by an electromagnetic flowmeter. The first or second diagonal branch of the left anterior descending coronary artery was cannulated and perfused from a carotid artery; inflow was abolished by embolization with latex microspheres (diameter: 25±5 ) and peripheral coronary pressure was assumed to represent CPP. Segmental coronary resistances were defined as follows: Proximal coronary resistance (R₁) was calculated from the difference between coronary perfusion pressure and CPP devided by coronary inflow. Distal coronary resistance (R₂) was calculated from CPP divided by coronary inflow. Reactive hyperemia was produced by interruption of coronary inflow for 15 s and analysed at 30 s and 60 s of reperfusion when cardiac function had recovered. At baseline, R₁ was 0.52±0.04 mm Hg x min ×100 g/ml (RU) and R₂ 0.63±0.07 RU. At 30 s, R₁ was reduced by 19±3% (P<0.01) this was less (P<0.05) than R₂ which was reduced by 32±3% (P<0.01). At 60 s R₁ and R₂ were reduced by 11±2% and 13±2%, respectively; this was not significantly different. Accordingly, CPP (baseline: 59±4 mm Hg) at 30 s was reduced by 7±2% (P<0.03), at 60 s the reduction was not significant. The data suggest that reactive hyperemia, as a model of metabolic coronary dilatation, may reduce CPP equivalent to a coronary steal phenomenon.     

The control of sodium metabolism to maintain osmo- and volumehomeostasis

Summary Chronically instrumented female beagles were maintained in standardized environmental and dietary conditions allowing careful examination of the mechanisms governing sodium homeostasis. The experimental increase in left atrial pressure (obtained by a reversible mitral stenosis) is accompanied by an increase in sodium excretion (atrial natriuresis, AN). AN served as an experimental manoeuvre from which the mechanisms governing sodium homeostasis could be elucidated. The results allow the following conclusions: (1) The signals arising from distension of the left atrium (e.g. expansion of the extracellular fluid volume) appear not to be a necessary prerequisite for the maintenance of sodium homeostasis. (2) The control mechanisms seem to be very sensitive to changes in total body sodium (TBS). A small reduction in TBS abolishes sodium eliminating processes e.g. saline diuresis, osmotic diuresis, AN. (3) It is probable that a natriuretic factor exists for sodium elimination. In summary, total body sodium appears to be controlled by a series of redundant mechanisms which guarantee an appropriate strategy for the comfort and ultimate survival of the organism. At the moment it is impossible to quantitate the contributions made by the various mechanisms in the control of sodium metabolism.     

Regional blood flow in response to exercise in conscious dogs

Summary Regional blood flow was measured with the microsphere method in conscious dogs under resting conditions and during moderate exercise on the treadmill.With respect to total organ blood flow, exercise induced a marked increase in blood flow to the calf muscles and to the myocardium, and a significant decrease in the arterial blood supply to the liver. Slight changes in blood flow to the other organs under study (various skeletal muscles, skin, brain, kidneys, intestine) were not significant.Study of the blood flow distribution within the myocardium showed a slight decrease of the ratio of subendocardial to subepicardial blood flow in the left ventricular free wall in response to exercise, and within the brain there was a relative increase in the blood flow to the cerebellum.     

Independent regulation of atrial coronary blood flow by atrial contraction rate in conscious dogs

Summary The effects of separate increases in atrial and ventricular contraction rates on the distribution of coronary flow within the heart were determined in conscious dogs with chronic heart block. Atrial tachycardia increased atrial blood flow and did not change ventricular blood flow. Ventricular tachycardia increased ventricular blood flow but not atrial blood flow. The results are consistent with the concept of local regulation of coronary perfusion by local myocardial energy turnover. The results also call attention to a potential adverse impact of atrial tachyarrhythmia in patients with underlying coronary ischemia.     

The effect of saline loading and subsequent anaesthesia on thoracic duct lymph,transcapillary protein escape and plasma protein of conscious dogs

The effect of saline infusion (up to 7 h) and subsequent anaesthesia (5 h) (halothane) or muscle relaxation (3 h) on thoracic duct lymph flow (LF), protein concentration (LP), albumin to glubulin ratio (LAG), transported protein (LTP), plasma volume (PV), intravascular protein pool (IVP) and plasma disappearance rate of radioalbumin (k) was studied in conscious dogs with a chronic thoracic duct-venous shunt.Saline infusion increased LF by 150%, decreased LP by 23% and LAG by 8%, LTP was enhanced by 99%. PV was elevated by 28%, IVP by 6% andk by 22%. Extravascular tracers showed an increase in lymph flow from the muscles and intestine and possibly from the liver.Anaesthesia reduced LF by 58%, increased LP by 30%, LAG was not changed significantly and LTP was decreased by 50%. PV and IVP were decreased after 3 h of anaesthesia by 11% and 4%, respectively, andk was not changes significantly. After 5 h of anaesthesia, PV, IVP andk were reduced by 13%, 6% and 35%, respectively. The use of an extravascular tracer indicated a nearly complete cessation of muscular lymph drainage.Relaxation of conscious saline loaded dogs yielded results similar to those obtained under anaesthesia.The data show that capillary protein leakage and lymphatic return are impaired in saline loaded dogs during anaesthesia because of an inactivation of the tissue pump. The intrinsic contractions and/or the vis a tergo seem unable to maintain an adequate muscular lymph drainage and, consequently, oedema develops, which increases tissue pressure until it counterbalances filtration pressure, and capillary filtration and lymphatic return come into equilibrium.Thoracic Duct Lymph and Saline LoadingPresented in part at the 45th meeting of the Deutsche Physiologische Gesellschaft [33]Supported by the Deutsche Forschungsgemeinschaft     

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]     

Atrial natriuretic peptide attenuates pressor but enhances natriuretic responses to angiotensin II in pregnant conscious goats

This study was designed to examine the actions of ANP in acute, ANGII-mediated hypertension during pregnancy. Effects on blood pressure, blood volume, and renal Na and K excretion were evaluated in conscious goats (n= 6). ANP (2 μrg min^-1), ANGII (0.5 μg min^-1), or ANGII + ANP (doses the same as for each peptide alone) was infused intravenously for 60 min. The pressor response to ANGII was reduced in pregnant goats. This reduction was seen in systolic, but not in diastolic pressure. ANP decreased pressure by 5–10 mmHg both in pregnancy and in non-pregnancy. When ANGII + ANP was infused, blood pressure initially rose as with ANGII but then declined. ANP suppressed only the elevated systolic pressure. Plasma protein concentration and haematocrit was reduced by ANGII but increased by ANP alone or together with ANGII, thereby implying fluid shift into the vasculature by ANGII and opposite movement by ANP. ANGII increased renal Na excretion to 1500 μmol min^-1in non-pregnancy, but only to half of that in pregnancy. ANP alone caused small natriuresis, but enhanced ANGII-induced natriuresis to near 3000 μmol min^-1in both non-pregnant and pregnant goats. In summary, ANP further attenuated the blunted blood-pressure rise due to ANGII in pregnant goats, and reduced plasma volume, but enhanced renal Na excretion as in non-pregnant goats. This implies that with the present combination ANP and ANGII caused a near maximal natriuretic response that was not modified by the systemic cardiovascular changes occurring in pregnant goats.     

Responsiveness of the ANP providing system to volume load in conscious dogs

We examined in detail changes in arterial plasma ANP concentration in response to volume load in conscious dogs. In a 5-min volume load experiment, 18 ml/kg of isosmotic and isooncotic 3% Dextran 40 in saline was infused over a period of 5 min. Mean left atrial pressure (MLAP) increased transiently by 7.6±0.9 mm Hg. Plasma ANP level (P-ANP) did not significantly increase. Assayed P-ANP levels were corrected for hemodilution. Corrected P-ANP (C-ANP) significantly increased from 206±17 to 348±34 pg/ml. However, the level of C-ANP did not reach a steady state. No significant linear correlation was found between increases in MLAP and normalized C-ANP. In a 45-min volume load experiment, the elevated level of MLAP caused by the 5-min volume load was maintained for 40 min by supplemental infusion. C-ANP significantly increased from 196±18 pg/ml to 435±73 ng/ml. The level of C-ANP reached a steady state. A close linear correlation was observed between increases in MLAP and normalized C-ANP. However, the peak time of C-ANP lagged 10 min behind MLAP. These results indicate that it takes 10 min for P-ANP to reach a steady state in fully responding to a volume load, and that the long-term volume load is a prerequisite to the response of the ANP providing system.