Diurnal rhythms of blood pressure, heart rate, and locomotor activity in adult and old male Wistar rats

The diurnal rhythms of systolic blood pressure (SBP), diastolic BP (DBP), heart rate (HR), and spontaneous locomotor activity (SLA) were determined in adult (6-month-old) and old (24-month-old) male Wistar rats by using radiotelemetry. The rhythm parameters (mesor, amplitude, acrophase, and percent rhythm) were analyzed by Fast-Fourier Transform and Cosinor methods. We found that the 12-h mean values of SBP, DBP, HR, and SLA were significantly (p<0.001) higher in the dark phase than in the light phase in both adult and old rats. The nocturnal 12-h mean value of HR was significantly (p<0.01) lower in old than in adult rats. In addition, the differences between diurnal and nocturnal 12-h mean values of SBP and HR were reduced in old rats. There was no significant difference in the 12-h mean values of SBP, DBP, and SLA between old and adult rats. Otherwise, the diurnal HR rhythm amplitude was significantly (p<0.01) reduced in old rats (32+/-2 vs. 46+/-2 bpm). A nearly 1-h delay in SBP and DBP acrophases (03h55 +/- 00h19 vs. 02h57 +/- 00h14 and 03h17 +/- 00h13 vs. 01h53 +/- 00h22, respectively) was found in old rats comparing to adult rats. No significant change in SLA diurnal rhythm was observed in old rats. In conclusion, these results show a decrease in the nocturnal 12-h mean value of HR and an alteration in cardiovascular diurnal rhythms by a 1-h delay of SBP and DBP acrophases and a reduction of HR rhythm amplitude in old Wistar rats.     

Depolarization pattern of ventricular epicardium in two-kidney one-clip hypertensive rats

The present study is the first attempt to examine the effect of left ventricular hypertrophy (LVH) on the excitation pattern of the ventricular epicardium in experimental hypertensive rats. The left renal artery was clipped in Wistar rats (n = 8; 6-8 months old; weight, 174-295 g) to produce two-kidney one-clip (2K1C) hypertension. After 4 weeks, blood pressure was measured, and epicardial potential mapping was performed under sinus rhythm from 64 unipolar electrodes regularly distributed over the ventricular epicardium. Systolic blood pressure was approximately 40% higher in the rats with a clipped renal artery (162 +/- 14 mmHg, mean +/- s.d.) than in the normotensive rats (115 +/- 3 mmHg). LVH (approximately 23% increase in the ratio of the left ventricular weight to the body weight, P < 0.05) was observed in the 2K1C hypertensive rats. The depolarization pattern of the ventricular epicardium in the normotensive rats was similar to that in the rats with 2K1C hypertensive LVH. The duration of ventricular epicardial activation was shown to increase (approximately 35%, P < 0.05) in the hypertensive rats as compared to the normotensive animals. This study provides an explanation for alterations of the body surface potential distribution in hypertensive patients with LVH.     

Changes in basal secretion rates of thyroxine and 3,3',5-triiodothyronine from the thyroid gland during aging of the rat.

The present experiments were carried out to examine age-related changes in the basal secretion rates of both thyroxine (T4) and 3,3',5-triiodothyronine (T3) from the thyroid gland. The experiments were performed on male Wistar rats of three different ages, i.e., (1) adult rats of 6-8 months old, (2) middle-aged rats of 25-26 months old, and (3) aged rats of 28-30 months old. The rats were anesthetized with 1.0% halothane. The thyroid venous blood as well as systemic arterial blood was collected and secretion rates of both immunoreactive T4 (iT4) and T3 (iT3) from the thyroid gland were calculated from the differences in concentrations of iT4 and iT3 in these two blood plasmas, and from the flow rate of thyroid venous blood plasma. The secretion rates of thyroid iT4 in the three different age groups were as follows: 483 +/- 68 pg/min (mean +/- S.E.) in the adult rats, 598 +/- 104 pg/min in the middle-aged rats, and 491 +/- 150 pg/min in the aged rats. There were no significant differences among the secretion rates of thyroid iT4 in these rats. The secretion rates of thyroid iT3 in the groups were as follows: 36.2 +/- 7.5 pg/min in the adult rats, 58.9 +/- 13.9 pg/min in the middle-aged rats, and 61.3 +/- 7.6 pg/min in the aged rats. The secretion rates of thyroid iT3 in both middle-aged and aged rats were approximately 1.6-1.7 times as high as the value in adult rats (p less than 0.05). These results indicate that the thyroid secretion of iT4 is well maintained, while that of iT3 increases during aging.     

Complement enhances the clearance of large-sized soluble IgA aggregates in rats

In the present study the involvement of the complement system (C) in the clearance of soluble IgA aggregates in the rat was studied. Monoclonal monomeric IgA (mIgA) antibody (which does not activate C) or aggregated polymeric IgA (aIgA; which activates C) were administered intravenously to phosphate-buffered saline-treated and complement-depleted [Cobra venom factor (CVF)-treated] rats and assessed for clearance from the circulation. In control rats, mIgA was cleared in a biphasic fashion with a first half-life (T1/2) of 29.5 +/- 14.2 min and a second T1/2 of 230 +/- 176 min. No differences were observed in clearance of mIgA in CVF-treated rats as compared to PBS-treated rats. In PBS-treated rats, aIgA with a size between 20 S and 150 S disappeared very rapidly from the circulation with a first T1/2 of 1.1 +/- 0.4 min and a second T1/2 of 23.2 +/- 11.3 min. In CVF-treated rats the clearance of aIgA was significantly delayed as compared to that in control rats, namely with a first T1/2 of 7.3 +/- 2.6 min and a second T1/2 of 64.2 +/- 19.4 min. Immunohistochemical studies of the liver (which is the main site of clearance of aIgA) revealed that Kupffer cells (KC) are mainly responsible for the uptake of aIgA. Furthermore, in PBS-treated rats aIgA deposition was accompanied by C3 deposition in the KC. In CVF-treated rats, the percentage of KC containing aIgA was significantly lower during the first 16 min after aIgA administration as compared to PBS treated rats. In addition no detectable C3 was found in KC of CVF-treated rats. These results indicate that KC play an important role in the clearance of large molecular weight IgA in rats and that C facilitates the clearance of these complexes from the circulation.     

Long-term effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki rat.

In vivo biotelemetry studies have demonstrated a variety of heart rhythm disturbances in type 1 diabetes mellitus. In the streptozotocin (STZ)-induced diabetic rat, these disturbances have included reductions in heart rate (HR) and heart rate variability (HRV) and an electrocardiogram that displays prolonged QRS duration and Q-T interval. The aim of this study was to investigate the chronic effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki (GK) rat. Transmitter devices were surgically implanted in the peritoneal cavity of young male GK and age-matched Wistar control rats. Electrodes from the transmitter were arranged in Einthoven bipolar lead II configuration. Electrocardiogram, physical activity and body temperature data were recorded in rats from age 2 to 15 months. Data were acquired for 2 weeks each month. Non-fasting blood glucose, glucose tolerance and body weight were measured periodically. In GK rats, growth rate and maximal attained body weight were significantly reduced and non-fasting blood glucose was progressively increased compared with age-matched Wistar control animals. Heart rate was significantly lower in GK compared with control rats at 2, 7 and 15 months of age. At 2 months of age, HR was 316 +/- 6 beats min(-1) in GK rats compared with 370 +/- 7 beats min(-1) in Wistar control animals. There was a progressive age-dependent decline in HRV in Wistar control rats; however, HRV in GK rats did not alter significantly with age. Heart rate variability was significantly reduced in GK compared with Wistar control rats at 2 and 7 months. At 2 months of age, HRV was 28 +/- 2 beats min(-1) in GK rats compared with 38 +/- 3 beats min(-1) in Wistar control rats. Reduced HR in GK rats may be an inherited characteristic. The absence of age-dependent reductions in HRV in GK rats may be a consequence of an underlying impairment of autonomic control which manifests at early age.     

TGF-beta1 inhibits protracted-relapsing experimental autoimmune encephalomyelitis by activating dendritic cells

Protracted-relapsing experimental autoimmune encephalomyelitis (PR-EAE) in DA rats is an animal model closely related to multiple sclerosis (MS). Previous studies showed that nasal administration of TGF-beta1 suppressed the development and relapse of PR-EAE clinically and pathologically. Here we demonstrate that this suppressive effect was associated with activation of dendritic cells (DC), showing elevated proliferative response and IFN-gamma and nitric oxide (NO) production by DC. DC derived from TGF-beta1-treated rats with PR-EAE also showed high expression of nitric oxide synthase 2 (NOS2) at both mRNA and protein levels. Apoptotic cells were increased in spleen sections of TGF-beta1-treated rats compared to control rats. In studying mechanisms of apoptosis in TGF-beta1-treated rats, in vitro experiments demonstrated that TGF-beta1-treated DC induced apoptosis of CD4(+)T cells by a NO pathway after co-culture with T cells. These results support the hypothesis that TGF-beta1-induced suppression of PR-EAE is associated with apoptosis of CD4(+)T cells induced by DC-derived NO.     

Aging alters opiate inhibition of potassium (K+)-stimulated dopamine release from the corpus striatum of male rats

The effect of Leu-enkephalin (Leu-ENK), Met-enkephalin (Met-ENK), and naloxone on potassium (K+)-evoked endogenous dopamine (DA) release from striatal tissue fragments was examined in young (2-4 month) and old (20-25 month) male rats. The K(+)-evoked DA release was significantly lower in old compared to young animals. Leu-ENK significantly reduced K(+)-evoked DA release in young animals, but neither opiate affected DA release in old animals. Naloxone, which had no effect in young animals, raised the K(+)-evoked DA response in old animals to levels seen in young control preparations. These results suggest that the age-dependent decrease in K(+)-evoked DA release may in part be due to a stronger opiate inhibitory tonus in the CS of older rats.     

Carotid-sinus baroreflex modulation of core and skin temperatures in rats: an open-loop approach

The neural mechanisms of the thermoregulatory control of core and skin temperatures in response to heat and cold stresses have been well clarified. However, it has been unclear whether baroreceptor reflexes are involved in the control of core and skin temperatures. To investigate how the arterial baroreceptor reflex modulates the body temperatures, we examined the effect of pressure changes of carotid sinus baroreceptors on core and skin temperatures in halothane-anesthetized rats. To open the baroreflex loop and control arterial baroreceptor pressure (BRP), we cut vagal and aortic depressor nerves and isolated carotid sinuses. We sequentially altered BRP in 20-mmHg increments from 60 to 180 mmHg and then in 20-mmHg decrements from 180 to 60 mmHg while measuring systemic arterial pressure (SAP), heart rate (HR), and core blood temperature (T(core)) at the aortic arch and skin temperature (T(skin)) at the tail. In response to the incremental change in BRP by 120 mmHg, SAP, HR, and T(core) fell by 90.3 +/- 5.1 mmHg, 60.3 +/- 10.5 beats min(-1), and 0.18 +/- 0.01 degrees C, respectively. T(skin) rose by 0.84 +/- 0.10 degrees C. The maximum rate of change per unit BRP change was -2.1 +/- 0.2 for SAP, -1.5 +/- 0.4 beats min(-1) mmHg(-1) for HR, -0.003 +/- 0.001 degrees C mmHg(-1) for T(core), and 0.011 +/- 0.002 degrees C mmHg(-1) for T(skin). After the administration of hexamethonium or bretylium, these baroreflexogenic responses were completely abolished. We concluded that T(core) and T(skin) are modulated by the arterial baroreceptor reflex.     

Basal and stimulated plasma atrial natriuretic peptide (ANP) concentrations and cardiac ANP contents in old and young rats.

To investigate the ability of the ageing heart to release atrial natriuretic peptide (ANP) we compared the response of awake, trained, chronically catheterized old (20-21 months) and young (4 months) rats to an acute, hypertonic saline challenge. There were no differences between young and old rats in basal plasma concentration of sodium (PNa; old: 141 +/- 3 meq/l; young: 143 +/- 3 meq/l) or ANP (old: 61 +/- 5 pg/ml; young: 67 +/- 12 pg/ml). Five minutes after acute saline challenge, PNa rose in both groups (old: 146 +/- 2 meq/l; young 149 +/- 1 meq/l) and approximately 3-fold increases in plasma ANP levels (182 +/- 24 pg/ml; young: 179 +/- 42 pg/ml). Hearts of old and young rats were assayed for atrial and ventricular ANP content. Atrial ANP levels were similar in old and young rats (13.5 +/- 3.6 vs. 24.9 +/- 8.7 micrograms/g atrial tissue), whereas ventricular ANP content was approximately 4-fold higher in old vs. young rats (153.7 +/- 39.3 vs. 47.5 +/- 6.4 ng/g ventricular tissue). Thus, the ageing rat heart responds equally as well as the young rat to an acute NaCl challenge.     

Plasmic membranes of hepatocytes and adrenocorticocytes in rats of different ages: effect of testosterone.

Experiments on adult (6-8-month-old and 26-28-month-old) Wistar rats revealed the hyperpolarization of plasmic membranes and activation of Na,K-ATPase of adrenocorticocytes in animals of both age groups and of hepatocytes of adult rats. No effect of testosterone was observed on the level of membrane potential and the activity of Na,K-ATPase of hepatocytes of old rats. The effect of testosterone was prevented by inhibitors of protein biosynthesis (actinomycin D and cycloheximide) and a specific inhibitor of Na,K-ATPase (ouabain), but not by K(+)-channel blocker 2-aminopyridine. Testosterone was assumed to synthesize the specific factor, capable of activating Na,K-ATPase of plasmic membranes. The cytosole of hepatocytes and the blood serum of adult testosterone-treated rats activated the Na,K-ATPase of isolated plasmic membranes of hepatocytes of adult and old intact rats. During aging there was a decrease in the capacity of cells to synthesize the specific factor, which activated Na,K-ATPase of plasmic membranes.     

Effect of anoxia on intracellular and extracellular potassium activity in hypoglossal neurons in vitro

1. A brain slice preparation was used to study the hypoglossal (XII) neuronal response to anoxia. Both intra- and extracellular potassium activities (K+i,K+o) were measured by the use of ion-selective microelectrodes, and K+ flux was assessed by the use of pharmacologic blockers. 2. Extracellular recordings showed that a short period of anoxia (4 min) induced an increase in K+o of 26.4 +/- 7.5 mM (mean +/- SD, n = 20) in the XII nucleus of adult rats. 3. Intracellular recordings (n = 31) in XII neurons showed a substantial decrease in K+i during anoxia. Fourteen neurons were analyzed in detail and these showed that XII neurons depolarized to -25.3 +/- 7.7 mV, whereas K+i dropped from 93.6 +/- 14.9 to 32 +/- 9.0 mM. These results strongly suggested that K+ is lost from XII neurons during anoxia. 4. Although the extracellular space (ECS) shrank by approximately 50% during anoxia, the possibility that the increase in K+o and decrease in K+i were mainly caused by shrinkage of the ECS and swelling of intraneuronal space was excluded to a great degree because the changes in K+i and K+o during anoxia were relatively very large. 5. To study the mechanisms by which K+ is lost from XII neurons, we used several pharmacologic blockers. High concentration of ouabain (10 mM) and strophanthidin (80 microM) increased K+o from baseline (3-4 mM) to 40.9 +/- 2.5 mM (n = 6) but did not abolish an additional anoxia-induced increase in K+o, suggesting that mechanisms other than Na(+)-K(+)-adenosine triphosphatase inhibition were also responsible for the anoxia-induced K+ leakage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of the Potassium Channel Blocker Barium on Sodium and Potassium Transport in the Rat Loop of Henle In Vivo

In vitro evidence suggests that the 'recycling' of K(+) ions through luminal K(+) channels in the thick ascending limb of the loop of Henle (TALH) is essential for the normal operation of the luminal Na(+)-K(+)-2Cl(-) co-transporter. In the present study these channels were investigated in vivo by perfusing superficial loops of Henle in anaesthetised rats with and without the K(+) channel blocker barium. Using a standard perfusate, intraluminal barium (5 mmol l(-1)) reduced sodium reabsorption (J(Na)) from 1887 +/- 50 to 1319 +/- 53 pmol min(-1) (P < 0.001). When the experiment was repeated using a low-Na(+) perfusate, designed to inhibit reabsorption in the pars recta (the initial segment of the loop of Henle), a similar reduction in J(Na) was observed (from 698 +/- 47 to 149 +/- 23 pmol min(-1), P < 0.001), strongly suggesting that the effect of barium is localised to the TALH. The magnitude of the reduction in J(Na) during blockade of K(+) channels confirms the importance of K(+) recycling in facilitating Na(+) reabsorption in the TALH in vivo. However, the reduction in J(Na) was not associated with a fall in the K(+) concentration of the fluid collected at the early distal tubule. When bumetanide, an inhibitor of the Na(+)-K(+)-2Cl(-) co-transporter, was included in the low-Na(+) perfusate, net K(+) secretion was observed. Addition of barium to this perfusate reduced, but did not abolish, the secretion, suggesting that bumetanide-induced K(+) secretion results partly from paracellular transport. Experimental Physiology (2001) 86.4, 469-474.     

In vivo evidence for reduced cortical glutamate-glutamine cycling in rats treated with the antidepressant/antipanic drug phenelzine

Converging evidence has indicated that hyperglutamatergic activity and GABAergic dysfunction may play important roles in the neurobiology and treatment of depression and other mood disorders. In this study, in vivo 1H[13C] magnetic resonance spectroscopy was used to quantify the effects of acute phenelzine administration on cortical energetics, glutamate neurotransmission, and GABA synthesis flux. The time-resolved kinetics of cortical [4-13C]glutamate, [4-13C]glutamine, and [2-13C]GABA turnover from i.v.-infused [1,6-13C2]glucose was measured at 11.7 T in alpha-chloralose anesthetized rats four hours after phenelzine treatment (10 mg/kg, i.p.) and in non-treated controls. The rate of the tricarboxylic acid cycle flux was not affected by phenelzine treatment compared with the non-treated group (0.46+/-0.05 vs. 0.50+/-0.05 micromol/g/min, respectively). The rate of the glutamate-glutamine cycling flux between neurons and glia in the phenelzine-treated group was significantly reduced (from 0.16+/-0.04 to 0.10+/-0.03 micromol/g/min), providing in vivo evidence that phenelzine attenuates glutamate neurotransmission. Following phenelzine treatment, the cortical GABA concentration increased significantly (from 1.02+/-0.17 to 2.30+/-0.26 micromol/g), while the GABA synthesis flux was unchanged (from 0.07+/-0.02 to 0.06+/-0.02 micromol/g/min). The possible role of augmented GABAergic function resulting from elevated GABA levels in the observed modulatory effect of phenelzine on the glutamate-glutamine cycling flux was discussed. The reduced glutamate-glutamine cycling flux observed in this study suggests that, in addition to its effects on monoaminergic and GABAergic systems, the attenuation of glutamate neurotransmission resulting from phenelzine administration may also contribute to its efficacy in the treatment of depression. This study is the first demonstration that the glutamate-glutamine cycling flux, which can be measured non-invasively in the human brain in vivo, was altered due to the action of a psychotropic drug.     

Influence of ethyl alcohol when given alone or in combination with potassium and/or magnesium supplements on ventricular fibrillation threshold levels in laboratory rats.

Five groups of rats were studied in an investigation to determine whether changes in the ventricular fibrillation threshold (VFT) occur when ethyl alcohol (EtOH) is given alone or in combination with K+ and/or Mg2+ supplements; the first group (n = 20) served as controls, the second (n = 18) was given only EtOH, the third (n = 18) EtOH+KCl, the fourth (n = 16) EtOH+MgCl2, and the fifth (n = 18) EtOH+MgCl2 + KCl for a 9 month period. Two rats from each group were killed on each day. One rat heart was perfused using the Langendorff apparatus and the other used for tissue electrolyte analyses. A significant fall in the mean VFT (9.7 +/- SD 1.9 mA vs 4.5 +/- 1.6 mA; P less than 0.0001) was noted in the rats given EtOH solution as drinking water for 9 months, and a significant increase in the VFT levels was seen in the Mg(2+)-supplemented group (9.7 +/- 1.9 mA vs 18.9 +/- 4.1 mA; P less than 0.0001) and in the K+ + Mg2+ supplemented group (9.7 +/- 1.9 mA vs 15.8 +/- 1.3 mA; P less than 0.0001) compared to controls. In addition, an increase in the heart rate was observed in the group supplemented with Mg2+ (213 +/- 8 beats/min vs 231 +/- 10 beats/min; P less than 0.0001) as well as in the group supplemented with K+ + Mg2+ (213 +/- 8 beats/min vs 222 +/- 10 beats/min; P less than 0.002) compared to controls. There was no significant change in the coronary blood flow (CF) in any group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Isoprenaline augments total myocardial K+ influx of the in-situ beating porcine heart

To determine the total rate of K+ flux into myocardial cells of the in-situ beating heart and how this influx is affected by beta-adrenoceptor stimulation, we measured 42K+ content in myocardial biopsies taken at intervals after an intra-atrial infusion of 42K+ before and during an i.v. isoprenaline infusion (20 micrograms min-1) in six anaesthetized, open-chest pigs. Determination of the total K+ influx during beta-adrenoceptor stimulation was initiated 10 min after the start of isoprenaline infusion, when the transient net myocardial K+ uptake had subsided. Total K+ influx increased from a control value of 414 +/- 42 to 1086 +/- 246 mumol 100 g-1 min-1 during isoprenaline infusion. A quantitatively smaller increase in K+ influx carried by the Na(+)-K+ pump has previously been demonstrated during isoprenaline infusion. Left ventricular dP/dt rose from 1350 +/- 146 to 4833 +/- 150 mmHg s-1, stroke volume remained unchanged, but heart rate and peak left ventricular systolic pressure rose as expected, by 52 +/- 4 and 32 +/- 4% respectively during isoprenaline stimulation. All haemodynamic parameters, total plasma K+ concentration and plasma 42K+ activity remained stable throughout each experimental period. The number of ouabain binding sites was 65.5 +/- 1.0 before and 66.9 +/- 1.6 nmol 100 g-1 during isoprenaline infusion (difference n.s.). The present data indicate that not only the K+ influx carried by the ouabain-sensitive Na(+)-K+ pump but also the influx through ouabain-insensitive pathways is increased during beta-adrenoceptor stimulation of the in-situ beating pig heart.     

Cardiac glycogen in long-evans rats: diurnal pattern and response to exercise.

The 24-h pattern of cardiac glycogen was determined in normally active, caged male Long-Evans rats. Relatively small fluctuation was observed during a 24-h cycle with maximal difference between mean values ranging from 3.41 +/- 0.28 (dark room) to 5.15 +/- 0.19 (light room) mg glycogen/g wet wt heart, suggesting that the substantial diurnal variation of cardiac glycogen reported in Wistar rats is not a universally observed phenomenon. Cardiac glycogen during and following a single bout of moderate running was compared to a bout of strenuous running in fed male Long-Evans rats. Moderate continuous running at 20 m/min for 30 min did not decrease cardiac glycogen below the average control level (4.09 +/- 0.10 mg glycogen/g heart) but did cause a short period of supercompensation, which reached a peak of 6.27 +/- 0.19 mg/g heart at 2 h postexercise. Strenuous running in bouts at 30 m/min over a 2-h period for a distance of 1,413 m caused a significant decrease in cardiac glycogen to 2.66 +/- 0.20 mg/g heart followed by an extended period of supercompensation, which reached a peak of 9.01 +/- 1.41 mg/g heart at 4 h postexercise and remained significantly elevated during the next 13 h. Thus, the severity of exercise in normal, fed rats determines not only the extent of cardiac depletion, but also the supercompensation pattern of glycogen repletion following exercise.     

Muscle myoglobin as determined by electrophoresis in thermally acclimated rat

Quantitative analysis of myoglobin (Mb) was established using the sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis in order to determine the influence of thermal acclimation on Mb levels in muscles. Myoglobin was measured in the red and white parts of quadriceps, soleus, diaphragm and heart of young adult male rats (11 weeks old). It was higher in the red muscle (0.92 +/- 0.043 mg/g fresh weight) than in the white muscle (0.08 +/- 0.007), and similar in the red muscle and soleus (1.17 +/- 0.117). Heart showed the highest level (1.52 +/- 0.073) among the tissues studied. The level in diaphragm (0.74 +/- 0.039) was intermediate between red muscle and heart. Cold acclimation (5 degrees C for 4 weeks, 11 weeks old) caused significant increases in Mb levels in white muscle (0.27 +/- 0.031, p less than 0.001), heart (1.95 +/- 0.094, p less than 0.01), and diaphragm (1.01 +/- 0.060, p less than 0.01), but not in red muscle and soleus. The rats reared in cold for many generations (20 generations at 5 degrees C, 11 weeks old) manifested significant increases in Mb levels of all tissues (p less than 0.05-0.001) examined. Heat acclimation (33 degrees C for 4 weeks, 11 weeks old) did not influence Mb levels of the tissues. The above findings suggest that skeletal muscle Mb may be partly involved in an enhanced thermogenesis in cold acclimation by favouring an oxidative capacity of muscles.     

Comparison of SA nodal and subsidiary atrial pacemaker function and location in the dog.

A 3-4 cm length of sulcus terminalis tissue including the sinoatrial node (SAN) was excised from 14 dogs. After an initial junctional rhythm with SAN excision a P wave emerged within days to weeks in 12 animals. Maximum heart rates of the SAN (preoperative) in response to exercise (276 +/- 15 beats/min), isoproterenol infusion in conscious animals (272 +/- 11 beats/min), and stellate stimulation during anesthesia (273 +/- 9 beats/min) were significantly greater than subsidiary pacemakers (postoperatively) for exercise (219 +/- 9 beats/min), isoproterenol (226 +/- 8 beats/min), and stellate stimulation (197 +/- 9 beats/min). During a final experiment, electrophysiological mapping of the area of earliest epicardial activation (pacemaker location) was carried out. By use of a suction electrode in reference to plunge electrodes located in the anterior interatrial band (AIB), eustachian ridge of the coronary sinus, and limbus of the fossa ovalis, the pacemaker was located at the inferior vena cava-inferior right atrial junction in 80% of the animals mapped. During isoproterenol infusion the foci shifted to regions of the AIB in 70% of the animals mapped. The concept of pacemaker hierarchy is discussed.     

Degradation of immunoreactive albumin in young and old conscious female rats

The kinetics of inactivation of plasma albumin was studied in young (3-4 months) and old (25-28 months) Sprague-Dawley female rats. Conscious, free-moving animals carrying indwelling atrial and carotid cannulas received a single injection of [125I]-albumin (rat) via the carotid cannula. Sequential blood samples were removed at intervals during the following 120 min, and total (TR) and immunoprecipitable radioactivity (IPR) were determined in the corresponding plasmas. TR disappearance curves for young and old animals were almost identical but IPR disappearance curves showed a significantly faster decline in the young rats. The absolute plasma volumes for young and old rats were (mean +/- S.E.M.), 10.8 +/- 1.1 and 14.4 +/- 1.5 ml, respectively (P less than 0.05). The IPR/TR ratio, an estimate of albumin inactivation within the plasma space, showed a monoexponential decrease in vivo with a t 1/2 of 11.4 +/- 5.1 and 39.3 +/- 10.8 h (P less than 0.05) for young and old rats, respectively. The in vitro t 1/2s for albumin were 5.25 +/- 1.02 and 3.42 +/- 0.91 days (NS) for young and old rats, respectively. It is concluded that: the rate of albumin catabolism declines with age in the female rat; albumin is mainly inactivated in the extravascular space; and total plasma volume increases significantly with age in this species.     

The effects of aging on somatocardiac reflexes in anesthetized rats

Nociceptive cutaneous stimulation produces a reflex tachycardiac response that is mediated through the activation of cardiac sympathetic efferents. This response includes reflex components of both supraspinal and spinal origin, depending on which segmental afferent area is stimulated (for a review see Sato et al.: Rev Physiol Biochem Pharmacol 130: 1-328, 1997). We herein examined the effects of aging on these supraspinal and spinal reflexes in anesthetized rats that were 4-7 (young adult), 24-27 (old), and 32-36 (very old) months of age. In central nervous system (CNS)-intact animals, we found that the supraspinal tachycardiac response induced by the pinching of a hindpaw was well preserved in old rats but was significantly attenuated in very old rats, while pinching-induced increases in cardiac sympathetic nerve activity were well maintained in both of these rat populations. In spinalized animals, spinal-mediated changes in heart rate (HR) and cardiac sympathetic nerve activity induced by the pinching of the chest skin were well preserved in both old and very old rats. There were no significant differences in resting HR among the 3 age groups studied, though the maximum HR induced by the beta-adrenergic agonist isoproterenol was reduced with age. The beta-receptor-mediated maximum HR was greater than that induced by pinching in young adult and old rats, CNS-intact and spinalized rats, and very old spinalized rats, while the maximum HR was nearly the same as the pinching-induced HR in CNS-intact very old rats. These results suggest that both supraspinal and spinal neural reflex pathways involved in the cardiac sympathetic response to cutaneous pinching are well preserved in older animals. They also suggest that the decline in the responsiveness of the heart to beta-adrenergic stimulation results in a reduced pinching-induced supraspinal tachycardiac response in very old rats.