Transient downregulation of glomerular atrial natriuretic factor receptors in high output heart failure in the rat.

OBJECTIVE: The renal response to exogenous atrial natriuretic factor (ANF) is blunted in chronic heart failure. The aim of the present studies was to investigate whether renal ANF receptor regulation in chronic heart failure is a time related event. METHODS: Glomerular ANF receptors were analysed in radioligand binding experiments at 0, 1, 2, 6, 12, 24, and 48 h, as well as at 1, 2, 4, and 8 weeks after the induction of an aortocaval shunt. RESULTS: Rats with aortocaval shunts had lower packed cell volume and body weight and higher relative heart weight than sham operated controls. Plasma ANF C and N terminal levels were increased in shunt rats as early as 5 min after establishment of the shunt. Right and left atrial ANF concentrations were decreased and ventricular ANF concentration was increased in shunt rats at 6 and 12 h respectively. Competitive inhibition of 125I-ANF binding showed that at 6 h the density (Bmax) of glomerular ANF receptors was significantly lower than in the controls [518(SEM 10) v 759(12) fmol.mg-1 protein] without differences in their affinity (Kd). The low Bmax in shunt animals persisted at 12, 24, and 48 h, even at 1 week [Bmax: 400(29) and 713(28) fmol.mg-1 protein; Kd: 80(2) and 70(4) pM, for AC rats and controls, respectively]. Bmax values were not significantly different at 2, 4, and 8 weeks. In 24 h animals, C-ANF displaced 65% of total binding, with both total and C ANF binding sites being 38% lower in shunt animals. CONCLUSION: Downregulation of glomerular ANF receptors is a transient event during the development of high output heart failure in the rat. Thus the blunted renal response to ANF during chronic heart failure is not likely to be due to a decrease in renal ANF receptor density or affinity.

Renal glomerular atrial natriuretic factor receptors in one-kidney, one clip rats.

One-kidney, one clip (1K1C) hypertension is often associated with an expanded plasma volume and (once the arterial clip is removed) with natriuresis. Blood pressure (BP), atrial and plasma concentrations of atrial natriuretic factor (ANF), hematocrit, and renal glomerular ANF receptors were therefore studied in 1K1C rats and in their normotensive uninephrectomized controls before and after unclipping. Six hours after removal of the clip, BP was normal in the 1K1C group and plasma ANF presented a sharp decline but was still significantly higher than in the normotensive controls, with a slight difference being evident 24 hours after unclipping. Hematocrit was lower in the 1K1C rats than in their control counterparts, but this difference tended to disappear once the clip was removed, indicating a contraction of plasma volume in these unclipped 1K1C animals. The renal glomerular ANF receptor population was markedly smaller in 1K1C rats than in the uninephrectomized controls but showed a twofold increase in number and affinity 24 hours after unclipping. It is concluded that the up-regulation and enhanced affinity of glomerular ANF receptors (probably secondary to the decrease in plasma levels of ANF) may contribute to the natriuresis reported in hypertensive 1K1C animals on removal of the arterial clip.

Glomerular atrial natriuretic factor receptors in spontaneously hypertensive rats.

There are differences in the renal handling of sodium between spontaneously hypertensive rats (SHR) and their normotensive controls. We investigated whether this difference may be associated with changes in plasma and tissue atrial natriuretic factor (ANF) levels and with alterations in glomerular ANF receptors at 4, 8, 12, and 16 weeks of age. Age-matched Wistar-Kyoto (WKY) and Wistar rats were used as normotensive controls. Systolic blood pressure was higher in SHR at 8, 12, and 16 weeks, and cardiac hypertrophy was also present in these animals at 4 weeks. Plasma ANF C- and N-terminal concentrations were greater than in both normotensive groups at 8 and 16 weeks. ANF in the right atrium was higher in SHR than in WKY rats and identical to that in the Wistar group at 4 and 8 weeks. ANF in the left atrium was lower in SHR than in both control groups at week 12. No differences were found in ventricular ANF content. The density of glomerular ANF binding sites increased with age in WKY and Wistar rats but not in SHR. At weeks 8, 12, and 16, both normotensive groups had a higher density of binding sites than SHR, but binding site affinity was greater in SHR at weeks 8 and 12. After incubation with increasing concentrations of ANF, the production of cyclic guanosine monophosphate (cGMP) by isolated glomeruli from 16-week-old rats was lower in SHR than in both normotensive groups. We conclude that the development of hypertension in SHR is associated with higher plasma ANF levels and decreased glomerular ANF receptor density and glomerular cGMP production.(ABSTRACT TRUNCATED AT 250 WORDS)

Downregulation of glomerular and vascular atrial natriuretic factor receptor subtypes by angiotensin II.

We have previously reported that pressor doses of angiotensin II induce atrial natriuretic factor (ANF) release. Since the number of glomerular and vascular ANF receptors may vary inversely with plasma ANF levels, we investigated whether they are modified by angiotensin II. Male rats were infused intraperitoneally for 7 days with either a non-pressor (200 ng/kg per min) or a pressor (800 ng/kg per min) dose of angiotensin II. Sham-infused animals served as controls. Blood pressure and plasma C- and N-terminal ANF were higher, and atrial ANF concentrations lower, in pressor than in either non-pressor or sham-infused groups. Glomerular ANF receptor density was lower in pressor than in either non-pressor or sham-infused animals. The production of cyclic guanosine monophosphate by isolated glomeruli was significantly lower in pressor than in either non-pressor or sham-infused groups. Vascular ANF receptor density was lower in pressor than in either sham-infused or non-pressor rats. No difference in affinity was observed in any group for either glomerular or vascular ANF receptors. Neither the density nor the affinity of glomerular and vascular ANF receptors were affected by prior washing of the membranes with an acid solution (pH 5.0). Irreversible cross-linking of 125I-ANF followed by sodium dodecylsulfate-polyacrylamide gel electrophoresis in reducing conditions and autoradiography demonstrated that both high- and low-molecular weight receptors were downregulated in glomerular membranes, but only the low-molecular weight receptor was reduced in vascular membranes after a high-dose infusion of angiotensin II. We conclude that angiotensin II induces a true downregulation of its glomerular and vascular receptor subtypes, probably by increasing plasma ANF levels. A direct or indirect effect of angiotensin II on ANF receptor regulation cannot be eliminated, however.

Atrial natriuretic factor: specific binding to renal glomeruli during the development of two-kidney, one clip hypertension in the rat.

Blood pressure (BP), atrial and plasma concentrations of atrial natriuretic factor (ANF), hematocrit and renal glomerular ANF receptors were studied during the development of hypertension in two-kidney, one clip (2-K, 1C) rats and were compared with normotensive controls. Plasma ANF was elevated in the 2-K, 1C group in all stages of hypertension, even after 3 weeks when BP, although higher than in sham-operated animals, had not yet reached arbitrarily-set hypertensive levels. At this time, hematocrit was higher in the hypertensive rats than in the controls, but the difference later disappeared. Lower atrial ANF concentrations were observed in the 2-K, 1C group at week 3, but only in the right atrium. No difference in ANF levels was noted in either the left or right atrium between hypertensive and normotensive animals 5 and 7 weeks after clipping. The glomerular ANF receptor population was markedly smaller in the clipped left kidney of 2-K, 1C rats during all stages of hypertension, and in the untouched right kidney at 5 and 7 weeks after surgery, but was larger in the non-clipped right kidney in the pre-hypertensive phase (3 weeks). It is concluded that receptor density changes during the evolution of high BP in the 2-K, 1C Goldblatt model of experimental hypertension. Our data suggest that the increases and decreases in density of renal glomerular ANF receptors may play a role in the differential handling of sodium by the clipped and non-clipped kidney during the various stages of development of 2-K, 1C hypertension in the rat.

Characterization of receptors for the atrial natriuretic factor in rat renal microvessels.

OBJECTIVE: To characterize [125I]-atrial natriuretic factor [ANF-(99-126)] binding sites in the renal preglomerular microvasculature of Sprague-Dawley rats. METHODS: Renal preglomerular microvessels were isolated by infusion of a magnetized iron oxide solution into the renal arteries and detachment from non-vascular tissue by a magnetic field. In order to characterize [125I]-ANF-(99-126) binding sites, saturation and competitive binding experiments were performed. To evaluate the proportions of ANF receptor subtypes (ANF-R1, ANF-R2), competition curves were charted in the presence of 10(-6) mol/l C-ANF-(4-23), a specific ligand of ANF-R2 (ANP-C). RESULTS: [125I]-ANF binding to vascular membranes was saturable and of high affinity. Equilibrium saturation binding curves suggested the presence of one group of high-affinity receptors [equilibrium dissociation constant (Kd) 22 +/- 6 pmol/l; binding capacity (Bmax) 118 +/- 6 fmol/mg protein]. In competitive inhibition experiments, no significant differences were found in binding capacity between experiments performed either in the presence or in the absence of an excess (1 mumol/l) of C-ANF (94 +/- 27 versus 151 +/- 35 fmol/mg protein, respectively), suggesting that most receptors in the renal vasculature are of the subtype ANF-R1. Incubation of renal microvessels with ANF-(99-126) stimulated cyclic GMP production in a dose-related manner. In parallel studies, the proportion of ANF-R1 (ANP-A, -B) and ANF-R2 (ANP-C) receptors in glomeruli, calculated from competitive inhibition experiments, was 86 +/- 2 and 14 +/- 2%, respectively (P < 0.005). CONCLUSIONS: These results indicate that rat renal preglomerular microvessels contain a high proportion of guanylate cyclase-coupled ANF-R1 (ANP-A, -B) and a low density of ANF-R2 (ANP-C) receptors. This difference in the proportion of ANF receptor subtypes, compared to that reported in glomeruli and other vascular beds, may have physiological significance.

Attenuation by propranolol of exercise training effects in spontaneously hypertensive rats.

The effects of propranolol (10 mg/kg) on systolic blood pressure (SBP), resting and exercising heart rates (HR), and body weight (BW) were examined in 11-week swim-trained spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. In both species, SBP was significantly reduced by either propranolol or training, but the reduction was greater with propranolol than with training. However, when propranolol was administered to rats during training, their independent beneficial effects on SBP were annulled. HR was modified slightly by propranolol and training, but they both decreased BW. The mechanism of propranolol action on BW is not clear. Maximum oxygen uptake (VO2 Max), relative heart weight (RHW), and absolute heart weight (AHW) were measured after 11 weeks of training. In both SHR and WKY rats, VO2 Max was elevated by exercise training; moreover, VO2 Max was greatest among those receiving propranolol while training. However, the combined effects of propranolol and training produced a significant reduction of AHW in SHR. The RHW was increased by training, but it was decreased by propranolol. SHR rats were more sensitive to the effects of training and propranolol than WKY rats. In humans, several observations have been reported on the attenuation of certain exercise-induced cardiovascular and metabolic changes by beta-adrenergic blocking agents. Our results obtained with rats confirm some of those observations. It would seem that the hypertensive strain of rats could serve as a model for the study of attenuation mechanisms by beta-adrenergic blockers.

Swim training in genetically hypertensive rats of the Lyon strain: effects on plasma lipids and lipoproteins.

We studied the effects of training by forced swimming on plasma lipid and lipoprotein concentrations in the Lyon genetically hypertensive rats (LH), its normotensive (LN) and low blood pressure (LL) controls. Training was carried out 5 days a week for 5 weeks. The duration of daily training sessions was increased 15 min per day, from 2 to 6 h/day. Following training low density lipoprotein-cholesterol (LDL-C) was significantly lower (P less than 0.01) in LL, and the very low density lipoprotein (VLDL-C) was also lower in LN (P less than 0.01) and LH (P less than 0.05) rats compared with their sedentary controls. High density lipoprotein-cholesterol (HDL-C) was not significantly increased after training in all strains. Compared with controls, plasma total cholesterol, plasma triglycerides and phospholipids were not modified by training. The reduction of LDL-C, VLDL-C as well as the increase of the HDL-C:VLDL-C ratio suggest a beneficial effect of training on atherosclerosis and perhaps coronary heart disease risk.

Cardiovascular effects of central injection of acetylcholine in anaesthetized dogs: a role for vasopressin release.

1. The effect of an intracisternal injection of 20 micrograms kg-1 of acetylcholine was studied on systolic and diastolic blood pressures, heart rate, and plasma levels of noradrenaline, adrenaline, vasopressin, plasma renin activity and atrial natriuretic factor in chloralose-anaesthetized dogs, 8 of which were normal and 7 with diabetes insipidus (deprived of vasopressin secretion by surgical lesion of the hypothalamoneurohypophysial system). 2. Acetylcholine significantly increased systolic and diastolic blood pressures in both groups of animals. However, the rise in blood pressure was significantly shorter lived in the dogs with diabetes insipidus. 3. Acetylcholine significantly increased plasma levels of noradrenaline but not adrenaline in control animals and in dogs with diabetes insipidus. Noradrenaline and adrenaline responses after acetylcholine were not different in the two groups of animals. 4. Acetylcholine induced a significant increase in vasopressin plasma levels only in control animals while in dogs with diabetes insipidus vasopressin remained at nearly undetectable levels. 5. Acetylcholine significantly increased atrial natriuretic factor plasma levels only in control dogs. 6. Although plasma renin activity increased in both groups of animals after the i.c. injection of acetylcholine, this change was not significant in any group. 7. These results suggest that, in the anaesthetized dog, the central injection of acetylcholine induces a rise in blood pressure through both an increase in sympathetic outflow and a release of vasopressin.

Central cardiovascular effects of acetylcholine in the conscious dog.

1. The effects of central cholinomimetic drugs on cardiovascular and vasoactive hormonal responses (blood pressure, heart rate, catecholamines, vasopressin, atrial natriuretic factor, neuropeptide Y plasma levels and plasma renin activity) were investigated in conscious Beagle dogs. For this purpose a catheter was chronically implanted into each dog's cisterna magna to allow repeated central injections in the awake animals. 2. Intracisternal acetylcholine (20 micrograms kg-1) significantly increased systolic and diastolic blood pressure. These changes were accompanied by an initial short term tachycardia followed by a long lasting bradycardia. Intracisternal acetylcholine also increased noradrenaline, adrenaline and vasopressin plasma levels, decreased plasma renin activity but did not modify plasma levels of neuropeptide Y and atrial natriuretic factor. 3. The effects of acetylcholine were completely abolished by pretreatment with intracisternal injection of the muscarinic antagonist, atropine (5 micrograms kg-1) but not by the intracisternal injection of the nicotinic antagonist, mecamylamine (25 micrograms kg-1). 4. The present results demonstrate that there are qualitative and quantitative differences between the central cardiovascular effects of acetylcholine in conscious dogs compared to what we previously reported, using a comparable protocol, in anaesthetized dogs. Under both conditions, we observed a central cholinergically mediated increase in blood pressure secondary to an increase in sympathetic tone and vasopressin release but these responses were shorter (less than 10 min) in the conscious dogs than in anaesthetized dogs (more than 10 min). Moreover, we detected in the response to the central cholinergic stimulation in the conscious dogs a significant increase in plasma adrenaline levels and biphasic changes in heart rate which were not described previously in the anaesthetized dog.

Counteraction of spaceflight-induced changes in the rat central serotonergic system by adrenalectomy and corticosteroid replacement.

The effects of a 17-day spaceflight duration on serotonergic measures in various parts of rat brain have been studied (flight-SHAM group). The contribution of the activation of the hypothalamo-pituitary-adrenal axis (HPA) related to the response of the central serotonin system was evaluated in adrenalectomized with chronic corticosterone replacement rats (flight-ADX+CORT group). These two groups of rats were compared to their respective ground-based controls. Physiological parameters (body, adrenal and thymus weights) and corticosterone levels were measured. In flight-SHAM group as compared to controls, adrenal hypertrophy and elevation in plasma corticosterone levels (174%) were observed, without change in thymus mass. In most brain areas studied, significant decreases in TRP, 5-HTP and 5-HIAA were found associated with lower levels of 5-HT in cortex, thalamus and striatum. Conversely, there were elevations in TRP, 5-HTP levels in striatum and increases in 5-HIAA/5-HT ratios, an index of 5-HT turnover, in cortex, striatum and olfactory bulb while the hypothalamus was the sole region where a fall was observed. In ADX rats with chronic corticosterone replacement these effects were not observed in the majority of brain areas. It is concluded that a 17-day spaceflight exerted an inhibitory effect on serotonin metabolism, probably by activation of the HPA axis. The results could not distinguish between the effects of microgravity and the stress associated with landing.

Cardiovascular variability and baroreceptor reflex sensitivity over a 14-day tail suspension in rats.

To verify whether a long-term weightlessness simulation was associated with development of cardiovascular deconditioning, male Wistar rats were tail suspended for 13 days and then removed for a 24-h recovery. Blood pressure (BP) and heart rate (HR) responses, their spectral properties, and the pharmacologically tested baroreceptor reflex sensitivity were studied throughout the suspension period and after removal from the tail suspension device. BP, HR, and their variability were not altered over the experimental period, and there were no indications of orthostatic intolerance on release from head-down suspension. Spectral properties of BP and HR were unchanged during the experiment, and tail suspension did not induce modifications in the baroreceptor reflex sensitivity. These results taken together suggest that cardiovascular deconditioning may not be developed even after long-term hindlimb suspension in rats, in contrast to humans exposed to actual or simulated weightlessness. Our results raise issue with the use of tail-suspended rats as a valid model for the study of alterations in cardiovascular function induced by spaceflight in humans.

Hormonal responses to exercise during moderate cold exposure in young vs. middle-age subjects.

The influence of moderate cold exposure on the hormonal responses of atrial natriuretic factor (ANF), arginine vasopressin (AVP), catecholamines, and plasma renin activity (PRA) after exhaustive exercise was studied in 9 young and 10 middle-aged subjects. Exercise tests were randomly performed in temperate (30 degrees C) and cold (10 degrees C) environments. Heart rate, oxygen consumption, and peripheral arterial blood pressure were measured at regular intervals. Blood samples were collected before and immediately after exercise at 30 or 10 degrees C. Plasma sodium and potassium concentrations as well as hemoglobin and hematocrit were measured, and the change in plasma volume was calculated. At rest and during exercise, oxygen consumption was similar during exposure to both temperate and cold temperatures. During submaximal exercise intensities, the rise in heart rate was blunted while the increase in systolic blood pressure was significantly greater at 10 than at 30 degrees C. The increases in plasma sodium and potassium concentrations after exhaustion were similar between environments, as was the decrease in plasma volume. In both groups, all plasma hormones were significantly elevated postexercise, with the AVP response similar at 10 and 30 degrees C. However, the norepinephrine and ANF responses were significantly greater while the PRA response was significantly reduced at 10 degrees C. In the middle-aged subjects the epinephrine response to exercise was higher at 10 than at 30 degrees C. The greater ANF and reduced PRA responses to exercise in the cold may have resulted from central hemodynamic changes caused by cold-induced cutaneous vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Investigation of hormonal effects during 10-h head-down tilt on heart rate and blood pressure variability.

Head-down tilt (HDT) bed rest was used in this study to achieve physiological manipulation of the plasma concentrations of atrial natriuretic peptide (ANP) and the hormones of the renin-angiotensin system. The purpose of this was to achieve a parallel with previous animal experiments in which blockade of the renin-angiotensin system caused significant increases in low-frequency spectral power of heart rate variability, presumably as a consequence of increased blood pressure variability, although this was not measured in these animal experiments. Eight healthy young men completed 10 h of seated control and 6 degrees HDT. To gain a more complete understanding of the interactions between hormonal and neural factors involved in cardiovascular regulation, we measured heart rate, systolic and diastolic pressure variabilities, plasma hormone concentrations, and blood flow to selected vascular beds by pulsed Doppler. Resting R-R interval was not significantly different between seated and HDT tests. Stroke volume and cardiac output were elevated in the first 1-2 h of HDT (P < 0.05), whereas each of systolic (P < 0.01) and diastolic (P < 0.0001) pressures was lower during HDT. Plasma ANP increased as much as 70% during HDT (P < 0.0001). Total variability in each of R-R interval and diastolic blood pressure was reduced during HDT (P < 0.001). Thus, at a time when plasma renin activity was decreased as much as 40% (P < 0.0001), there was in fact a decrease in the variability of R-R interval and diastolic blood pressure in contrast to the hypothesized increase such as found in previous animal experimentation. The data were compatible with tighter autonomic regulation of heart rate about the ideal mean value during HDT.

Fluid regulatory hormone response to exercise after coca-induced body fluid shifts.

To determine the effect of coca chewing on heart rate (HR), mean arterial blood pressure (MAP), and plasma volume and their relationship with the hormones regulating cardiovascular and body fluid homeostasis, 16 male volunteers were examined at rest and during 1 h of cycle exercise at approximately 75% of their peak oxygen uptake in two trials separated by 1 mo. One trial was performed after the subjects chewed a sugar-free chewing gum (Coca- trial), whereas the other was done after the subjects chewed 15 g of coca leaves (Coca+), with the order of the Coca- and Coca+ trials being randomized. Blood samples were taken at rest, before (R1) and after 1-h chewing (R2), and during the 5th, 15th, 30th, and 60th min of exercise. They were analyzed for hematocrit, hemoglobin concentration, red blood cell count, plasma proteins, and for the fluid regulatory hormones, including plasma catecholamines [norepinephrine (NE) and epinephrine], renin, arginine vasopressin, and the atrial natriuretic peptide (ANP). During the control trial (Coca-), from R1 to R2, there was no significant change in hematologic, hormonal, and cardiovascular status except for a small increase in plasma NE. In contrast, it can be calculated that coca chewing at rest induced a significant hemoconcentration (-3.8 +/- 1. 3% in blood and -7.0 +/- 0.7% in plasma volume), increased NE and MAP, and reduced plasma ANP. Chewing coca before exercise reduced the body fluid shifts but enhanced HR response during exercise. These effects were not accompanied by changes in NE, epinephrine, renin, and arginine vasopressin plasma levels. In contrast, plasma ANP response to exercise was lower during the Coca+ trial, suggesting that central cardiac filling was reduced by coca use. It is likely that the reduction in body fluid volumes is a major contributing factor to the higher HR at any given time of exercise after coca chewing.

Cardiac and plasma atrial natriuretic peptide after 9-day hindlimb suspension in rats.

To determine atrial natriuretic peptide (ANP) adaptation to simulated weightlessness, immunoreactive plasma (ir-NH2- and ir-COOH-terminals) and atrial (ir-COOH-terminal) ANP levels, atrial mRNA expression, immunoreactive cardiocyte ANP levels (ir-NH2- and ir-COOH-terminals), and ultrastructural observations of granules in atrial cardiocytes were assessed in male Wistar rats after a 9-day hindlimb suspension. Plasma ir-NH2- and ir-COOH-terminal ANP concentrations decreased by 17 (P < 0.05) and 37% (P < 0.05), respectively, in suspended rats. A concomitant ir-COOH-terminal ANP content reduction was also observed in left (31%; P < 0.01) and right atria (25%; P < 0.05). Atrial ANP mRNA expression was severely depleted in the right atrium and less so in the left atrium after 9 days of hindlimb suspension. Immunocytochemistry observations demonstrated lowered NH2- and COOH-terminal ANP immunoreactivities in left and right atria from suspended rats. A reduced number of storage granules (dense granules) in both atria was also noted on ultrastructural analysis. It was concluded that ANP biosynthesis, storage, and release were decreased after a 9-day hindlimb suspension.

Restraint vs. hindlimb suspension on fluid and electrolyte balance in rats.

To determine the effect of hindlimb suspension on body fluid volume, salt and water balance, and relevant hormones, two series of experiments were performed in an experimental protocol including periods of isolation (7 days), horizontal attachment (7 days), and suspension (14 days). 1) During the first experiment, water and electrolyte balance, arginine vasopressin (AVP), and guanosine 3',5'- cyclic monophosphate (cGMP) were determined in urine, atrial natriuretic peptide in plasma and atria, and renin concentration and AVP in plasma in 30 rats. 2) During the second experiment, blood volume and extracellular fluid volume were measured by a dilution technique (Evans blue and sodium thiocyanate) in another 30 rats. We observed a pronounced and early effect of horizontal attachment on the renal variables. After 48 h, diuresis (49%), natriuresis (44%), kaliuresis (36%), osmotic load (39%), creatinine (28%), and AVP excretion (155%) were significantly increased in attached rats (P < 0.05). There was no short-term (24-h) effect of suspension on urine flow and Na+, K+, creatinine, and AVP excretion, but the urine cGMP decreased significantly (45%; P < 0.05). Significant decreases in natriuresis, kaliuresis, urine creatinine, and osmotic load occurred in the suspension group 7 days after suspension. After the 14-day tail suspension, plasma volume and extracellular fluid volume measured in suspended rats were not different from isolated rat values, whereas plasma volume increased by 15% (P < 0.05) in the attached rats. Plasma immunoreactive plasma atrial natriuretic levels of suspended rats were significantly reduced by 35% vs. isolated rats (P < 0.001) and by 18% vs. attached rats (P < 0.05). By using this experimental protocol, the physiological alterations revealed that suspension produced some acute and long-term effects, but the fixation to the suspension device, restraint, and confinement have their own influence on fluid distribution and renal function.

Central and peripheral sympathetic activities in rats during recovery from simulated weightlessness.

Rats were tail suspended, keeping their forelimbs weight bearing for 14 days, and then allowed to recover for a short (6-h) or a long (24-h) period to assess the behavior of the sympathetic nervous system after weightless simulation. Sympathetic activity was determined by measuring norepinephrine (NE) turnover in the brain stem cell groups involved in central blood pressure control and in organs playing a key role in the cardiovascular regulation (heart and kidneys). The NE turnover was greatly reduced in the rostral (-56%; P < 0.001) and caudal (-73%; P < 0.001) A2 nucleus of suspended rats but was unchanged in the A1, A5, and A6 cell groups compared with attached rats. The NE turnover in the cardiac atria (-34%; P < 0.001) and ventricles (-35%; P < 0.001) and kidneys (-31%; P < 0.001) was decreased after suspension. The central and peripheral sympathetic activities returned to normal within 24 h of release from suspension, but there was hyperactivity after 6 h of recovery. This raises the problem of interpreting the results obtained in animals killed a few hours after return from spaceflight.

Epinephrine, norepinephrine, and dopamine during a 4-day head-down bed rest.

Head-down bed rest at an angle of 6 degrees was used as an experimental model to simulate the hemodynamic effects of microgravity, i.e., the shift of fluids from the lower to the upper part of the body. The sympathoadrenal activity during acute (from 0.5 to 10 h) and prolonged (4 days) head-down bed rest was assessed in eight healthy men (24 +/- 1 yr) by measuring epinephrine (E), norepinephrine (NE), dopamine (DA), and methoxylated metabolite levels in their plasma and urine. Catecholamine (CA) and methoxyamine levels were essentially unaltered at any time of bed rest. Maximal changes in plasma were on the second day (D2): NE, 547 +/- 84 vs. 384 +/- 55 pg/ml; DA, 192 +/- 32 vs. 141 +/- 16 pg/ml; NS. After 24 h of bed rest, heart rate decreased from 71 +/- 1 to 63 +/- 3/min (P less than 0.01). Daily dynamic leg exercise [50% maximum O2 uptake (VO2 max)] used as a countermeasure did not alter the pattern of plasma CA during bed rest but resulted in a higher urinary NE excretion during postexercise recovery (+45% on D2; P less than 0.05). The data indicate no evident relationship between sympathoadrenal function and stimulation of cardiopulmonary receptors or neuroendocrine changes induced by central hypervolemia during head-down bed rest.

Fluid-regulating and sympathoadrenal hormonal responses to peak exercise following cardiac transplantation.

Orthotopic heart transplantation results in cardiac denervation that can disrupt the normal regulation of hydromineral balance. This study compared the exercise-induced variations in plasma osmolality; atrial natriuretic peptide (ANP), arginine vasopressin (AVP), norepinephrine (NE), epinephrine (E), and dopamine (DA) concentrations; and plasma renin activity (PRA) of six cardiac transplant recipients (HTX) and six healthy age-matched controls (C) submitted to graded upright maximal cycling. Venous blood samples were obtained at rest, at submaximal (70% O2 uptake) and peak exercise, and after 10 and 30 min of sitting recovery. Peak O2 uptake was not different between groups despite lower maximal heart rate in HTX (136 +/- 6 vs. 183 +/- 9 beats/min). Baseline plasma ANP and PRA were higher in HTX (203 +/- 55 pg/ml and 29.9 +/- 7.4 ng.ml-1 x h-1) than in C (71 +/- 17 pg/ml and 5.4 +/- 0.96 ng.ml-1 x h-1); AVP was lower in HTX than in C (1.1 +/- 0.3 vs. 3.2 +/- 0.8 pg/ml; P < 0.05); and circulating E, NE, and DA were not different between groups. Exercise resulted in more marked increases in HTX than in C for ANP (300 vs. 100%), AVP (2,000 vs. 300%), NE (860 vs. 500%), and DA (611 vs. 187%) but not for PRA and a higher E response in C than in HTX (455 vs. 1,258%). These observations confirm that the potential for ANP release to central volume loading is independent of intact cardiac innervation. The exaggerated AVP response in HTX could, however, reflect the absence of inhibitory influences consecutive to denervation.(ABSTRACT TRUNCATED AT 250 WORDS)