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Cyclooxygenase-1-deficient mice have high sleep-to-wake blood pressure ratios and renal vasoconstriction.

We used cyclooxygenase-1 (COX-1)-deficient mice to test the hypothesis that COX-1 regulates blood pressure (BP) and renal hemodynamics. The awake time (AT) mean arterial pressures (MAPs) measured by telemetry were not different between COX-1(+/+) and COX-1(-/-) (131+/-2 versus 126+/-3 mm Hg; NS). However, COX-1(-/-) had higher sleep time (ST) MAP (93+/-1 versus 97+/-2 mm Hg; P<0.05) and sleep-to-awake BP ratio (+8.6%; P<0.05). Under anesthesia with moderate sodium loading, COX-1(-/-) had higher MAP (109+/-5 versus 124+/-4 mm Hg; P<0.05), renal vascular resistance (23.5+/-1.6 versus 30.7+/-1.7 mm Hg . mL(-1) . min(-1) . g(-1); P<0.05) and filtration fraction (33.7+/-2.1 versus 40.2+/-2.0%; P<0.05). COX-1(-/-) had a 89% reduction (P<0.0001) in the excretion of TxB2, a 76% reduction (P<0.01) in PGE2, a 40% reduction (P<0.0002) in 6-ketoPGF1alpha (6keto), a 27% reduction (P<0.02) in 11-betaPGF2alpha (11beta), a 35% reduction (P<0.01) in nitrate plus nitrite (NOx), and a 52% increase in metanephrine (P<0.02). The excretion of normetanephrine, a marker for sympathetic nervous activity, was reduced during ST in COX-1(+/+) (6.9+/-0.9 versus 3.2+/-0.6 g . g(-1) creatinine . 10(-3); P<0.01). This was blunted in COX-1(-/-) (5.1+/-0.9 versus 4.9+/-0.7 g . g(-1) creatinine . 10(-3); NS). Urine collection during ST showed lower excretion of 6keto, 11beta, NOx, aldosterone, sodium, and potassium than during AT in both COX-1(+/+) and COX-1(-/-), and there were positive correlations among these parameters (6keto versus NOx; P<0.005; 11beta versus NOx; P<0.005; and NOx versus sodium; P<0.005). In conclusion, COX-1 mediates a suppressed sympathetic nervous activity and enhanced NO, which may contribute to renal vasodilatation and a reduced MAP while asleep or under anesthesia. COX-1 contributes to the normal nocturnal BP dipping phenomenon.

Aldosterone↗

Dose effects of human renin in rats transgenic for human angiotensinogen.

We examined the effect of chronic human renin infusion and human renin inhibition on blood pressure in a unique transgenic rat model. We infused incremental doses of human renin (1 to 500 ng/h) with minipumps for 10 days into rats harboring the human angiotensinogen gene [TGR (hAOGEN)1623]. We measured blood pressure and heart rate continuously by telemetry. We found that human renin at 5 ng/h was necessary to increase blood pressure, whereas 10 ng/h caused systolic blood pressure to increase to 215 +/- 13 mm Hg. Heart rate decreased initially but then increased by 100 beats per minute compared with basal values. Drinking behavior also increased. Doses as high as 500 ng/h did not increase blood pressure further. A linear relationship was found between the log of plasma renin activity and systolic blood pressure that increased in slope from days 2 to 9. Rat angiotensinogen levels were low and not influenced by human renin infusion. Human angiotensinogen levels remained stable until 500 ng/h human renin was infused, at which time they decreased by 50% at 9 days. Rat renin gene expression (RNase protection assay) was decreased by human renin infusion, whereas rat and human angiotensinogen gene expressions in liver and kidney as well as angiotensin-converting enzyme gene expression in kidney were not affected. The human renin inhibitor Ro 42-5892 was given by gavage repeatedly to rats receiving human renin at 40 ng/h. Ro 42-5892 lowered blood pressure promptly to basal values. High human renin hypertension in this model is dose dependent, features a steeper relationship between blood pressure and plasma renin activity over time, and is associated with tachycardia and increased drinking. We conclude that the human angiotensinogen transgenic rat offers new perspectives in the study of human renin-induced hypertension.

Angiotensinogen↗

Hepatic denervation chronically elevates arterial pressure in Wistar-Kyoto rats.

Several lines of evidence suggest that peripheral osmoreceptors respond to alterations in dietary NaCl by adjusting renal sympathetic nerve activity, but the impact of this reflex on the long-term regulation of mean arterial pressure (MAP) remains unclear. The present study tested the hypothesis that denervation of peripheral osmoreceptors elevates arterial pressure and induces NaCl-sensitive hypertension in normotensive rats. Hepatic denervated and sham-operated Wistar-Kyoto rats were instrumented with telemetry probes for continuous monitoring of MAP and heart rate. After 1 week on a basal (0.6%) NaCl diet, the rats were fed a high (8%) NaCl diet for 2 weeks. On the basal NaCl diet, MAP in hepatic denervated rats was 15+/-1 mm Hg higher than in sham-operated rats. The high NaCl diet did not significantly increase MAP above baseline levels in either denervated or sham-operated rats, but the amplitude of the 24-hour rhythm of arterial pressure increased significantly more in the denervated than in the sham-operated rats. In a second experiment, two similar groups of rats were fed a very low (0.05%) NaCl diet. Mean arterial pressure of the denervated group was significantly higher than that of the sham-operated rats on either the basal or the very low NaCl diet, but the very low NaCl diet did not affect arterial pressure in either group. These results suggest that in the rat, although hepatic osmoreceptors contribute to long-term arterial pressure regulation, they contribute much less to dietary NaCl-induced changes in arterial pressure.

Animals↗

Alterations in blood pressure and heart rate variability in transgenic rats with low brain angiotensinogen.

To study whether the brain renin-angiotensin system plays a role in the long-term and short-term control of blood pressure and heart rate variability, we examined in transgenic rats [TGR(ASrAOGEN)] with low brain angiotensinogen levels the 24-hour variation of blood pressure and heart rate. Telemetry recordings were made during basal and hypertensive conditions induced by a low-dose subcutaneous infusion of angiotensin II for 7 days. Short-term blood pressure and heart rate variability were evaluated by spectral analysis, and as a measure of baroreflex sensitivity, the average transfer gain between the pressure and heart rate variations was calculated. During the angiotensin II infusion in control but not TGR(ASrAOGEN) rats, the 24-hour rhythm of blood pressure was inverted (5.8+/-2 versus -0.4+/-1.8 mm Hg/group of day-night differences of blood pressure, P<0.05, respectively). In both the control and TGR(ASrAOGEN) rats, the 24-hour heart rate rhythms remained unaltered and paralleled those of locomotor activity. The transfer gain between 0.3 to 0.6 Hz was significantly higher in TGR(ASrAOGEN) than in control rats during control (0.71+/-0.1 versus 0.35+/-0.06, P<0.05) but not during angiotensin II infusion (0.6+/-0.07 versus 0.4+/-0.1, P>0.05). These results demonstrate that the brain renin-angiotensin system plays an important role in mediating the effects of angiotensin II on the circadian variation of blood pressure. Furthermore, these data indicate that a permanent deficiency in the brain renin-angiotensin system alters the reflex control of heart rate in rats.

Angiotensin II↗

Superoxide mediates sympathoexcitation in heart failure: roles of angiotensin II and NAD(P)H oxidase.

Chronic heart failure (CHF) is often associated with excitation of the sympathetic nervous system. This event is thought to be a negative predictor of survival in CHF. Sympathoexcitation and central angiotensin II (Ang II) have been causally linked. Recent studies have shown that NAD(P)H oxidase-derived reactive oxidant species (ROS) are important mediators of Ang II signaling. In the present study, we tested the hypothesis that central Ang II activates sympathetic outflow by stimulation of NAD(P)H oxidase and ROS in the CHF state. CHF was induced in male New Zealand White rabbits by chronic ventricular tachycardia. Using radio telemetry of arterial pressure and intracerebroventricular infusions, experiments were performed in the conscious state. Renal sympathetic nerve activity (RSNA) was recorded as a direct measure of sympathetic outflow. Intracerebroventricular Ang II significantly increased RSNA in sham (131.5+/-13.3% of control) and CHF (193.6+/-11.9% of control) rabbits. The increase in CHF rabbits was significantly greater than in sham rabbits (P<0.01). These responses were abolished by intracerebroventricular losartan, tempol, or apocynin. Resting RSNA was significantly reduced by intracerebroventricular losartan, tempol, or apocynin in CHF rabbits but not in sham rabbits. Intracerebroventricular administration of the superoxide dismutase inhibitor diethyldithio-carbamic acid increased RSNA significantly more in sham compared with CHF rabbits. NADPH-dependent superoxide anion production in the rostral ventrolateral medulla (RVLM) was increased by 2.9-fold in CHF rabbits compared with sham rabbits. Finally, increases in the RVLM mRNA and protein expression of Ang II type 1 (AT1) receptor and subunits of NAD(P)H oxidase (p40phox, p47phox, and gp91phox) were demonstrated in CHF rabbits. These data demonstrate intense radical stress in autonomic areas of the brain in experimental CHF and provide evidence for a tight relationship between Ang II and ROS as contributors to sympathoexcitation in CHF.

Angiotensin II↗

Plaque pH measurements by different methods on the buccal and approximal surfaces of human teeth after a sucrose rinse.

Changes in plaque pH after a sucrose rinse were simultaneously monitored by plaque sampling, touching of the plaque with antimony and glass electrodes, and telemetry. The minimum pH at approximal sites was approximately 0.7 pH units lower than that on buccal surfaces. The pH at the approximal site remained below resting levels after 120 min, and the area under the pH response curves from this site was five times greater than that from the buccal surfaces.

Dental Plaque↗

The measurement of dynamic compartment pressure during exercise.

Anterior tibial compartment pressures have been examined during exercise in nine healthy university students. Six male and three female subjects weighing 140 to 160 pounds and between 18 and 25 years of age were tested. A slit catheter was introduced into the muscle belly of the subjects' right anterior tibial compartment and dynamic compartment pressures measured using an F.M. telemetry system. Subjects were exercised on a treadmill at speeds from 1 to 6 mph and the variations in compartment pressure during one exercise cycle (one stride length) and over the course of the exercise period examined. Results have shown that both average and peak to peak pressures measured during exercise are much higher than those recorded at rest, and compartment pressures rose with increasing speed.

Adolescent↗

Circadian organization in a diurnal rodent, Arvicanthis ansorgei Thomas 1910: chronotypes, responses to constant lighting conditions, and photoperiodic changes.

Little information is available on circadian organization in diurnal mammals. In the present study, the daily patterns of wheel-running activity were described in a diurnal rodent, Arvicanthis ansorgei Thomas 1910, as assessed by karyological analysis. Among 108 animals born in the colony and studied under a 12:12 light-dark cycle (lights on at 7:00 a.m.), the authors determined the timing of daily activity (i.e., mean onsets and offsets of pattern of locomotor activity) and the level of wheel-running activity performed during daytime versus nighttime. The activity pattern was essentially diurnal in 84% of individuals, 46% being active only during the light period +/- 1 h (activity onsets and offsets at 6:20 a.m. and 7:40 p.m., respectively) and 38% being diurnal with a period of nocturnal activity longer than 1 h (activity onsets and offsets at 5:40 a.m. and 9:30 p.m., respectively). Of the 108 animals, 16% expressed a nocturnal activity with diurnal overlaps no longer than 1 h. In 6 diurnal individuals first exposed to constant light and then to constant dim red light, the endogenous period was shortened from 24.6 +/- 0.1 to 24.0 +/- 0.1 h, respectively. The numbers of wheel revolutions per day and during the active period remained unchanged between the two lighting conditions. In response to different photoperiodic changes from 16:08 to 08:16 light-dark cycles, the phase angle of photic synchronization, estimated by the daily onset of wheel-running activity in 6 diurnal animals, showed marked changes, its timing occurring 2 h before and 0.5 h after the onset of light under short and long photoperiods, respectively. The numbers of wheel revolutions per 24 h and during the active period were modified similarly according to photoperiodic changes. Finally, in 5 diurnal animals exposed to a 12:12 light-dark cycle, the daily pattern of general locomotor activity, determined by telemetry, was not modified by wheel availability. The data indicate that A. ansorgei is an interesting experimental model to understand the regulation of the circadian timing system in day-active species.

Animals↗

Stress-induced hyperthermia depends on both time of day and light condition.

Rats placed in an environment other than their home cage increase their body temperature (Tb) by more than 1 degree C. This stress-induced hyperthermia is considered to be a fever, in the sense that the Tb rise seems to reflect an upward shift in the level of regulated Tb (set point). The circadian rhythm of Tb also reflects changes in set point. One might therefore expect to see differences in response to such stress during various phases of the light-dark (LD) cycle as Tb fluctuates between L and D. To test this, 3- to 6-month-old male Long-Evans rats were taken from their home cages (12:12 LD) and placed individually in a Plexiglas container for 30 min. Tb and activity were measured via telemetry. In the first experiment, rats were placed in the container during day (from 1 to 3 h after lights on) and night (from 1 to 3 h after lights off), with light on or off during the test. There was a significant Tb rise in response to placement in the container at all times except when the rats were tested during the night with light on in the container; in that condition there was no Tb rise. In the second experiment, the authors determined that 30 min of light in the home cage before the test did not affect Tb: If the light was on in the test situation, hyperthermia was inhibited, and if it was off, hyperthermia was as high as control levels. In the third experiment, to determine whether this effect was time dependent, the test was performed at 4-h intervals, with light on or off during the test. The strongest inhibiting effect of light was in early night. In the fourth experiment, the authors turned the lights on during early night while the rats were in their home cages. This reduced their Tb significantly by less than 0.3 degrees C. The authors conclude that both clock time and light condition during testing are factors affecting the Tb rise in response to stress.

Animals↗

Natural entrainment without dawn and dusk: the case of the European ground squirrel (Spermophilus citellus).

Observational data collected in the field and in enclosures show that diurnal, burrow-dwelling European ground squirrels (Spermophilus citellus) never were above ground during twilight at dawn or at dusk. The animals emerged on average 4.02 h (SD = 0.45) after civil twilight at dawn and retreated in their burrows on average 2.87 h (SD = 0.47) before civil twilight at dusk. Daily patterns of light perceived by these burrowing mammals were measured with light-sensitive radio collar transmitters in an enclosure (the Netherlands) and in the field (Hungary). The observational data are corroborated by the telemetry data, which show clear daily patterns of timing of light perception including light perceived from the burrow entrances. The first light was observed by the animals on average 3.54 h (enclosure, SD = 0.45) and 3.60 h (field, SD = 0.31) after civil twilight at dawn, whereas the final observed light was on average 3.04 h (enclosure, SD = 0.64) and 2.02 h (field, SD = 0.72) before civil twilight at dusk. Thus, the animals do not perceive the rapid natural light-dark (LD) transitions that occur at civil twilight. Instead, they generate their own pattern of exposure to light within the natural LD cycle. The classical phase response model for entrainment by light or dark pulses cannot explain how the circadian system of this species remains entrained to the external, natural LD cycle while the major LD transitions are created by its own behavior.

Animals↗

Variation in daily masticatory muscle activity in the rabbit.

The daily use of masticatory muscles remains largely unclear, since continuous recordings were limited in space and time. This study's purpose was to use radio-telemetry to examine daily muscle use and its inter- and intra-individual variations. A telemetric device was implanted into the rabbit masseter, and the transmitted signals were digitally stored for 7 days. Muscle use was analyzed by calculation of the total time each muscle was activated above 5, 20, and 50% of the day's peak activity. Rabbits (n = 6) spent only 2% of the time chewing. Muscles were activated up to 20% of the total time at levels exceeding 5% of peak activity, and only about 0.5% of the time in forceful behaviors utilizing 50% of maximum contraction. It can be concluded that daily muscle use remained constant during succeeding days, but differed significantly among muscle regions and individuals.

Analysis of Variance↗

Adolescent ethanol sensitivity: hypothermia and acute tolerance.

A two-injection paradigm was used to assess acute (within-session) tolerance to ethanol in telemetry-implanted adolescent and adult rats. Male rats were intragastrically pretreated with either 1.0 g/kg of ethanol or water and then challenged with 2.0 g/kg of ethanol or water when blood alcohol levels (BALs) of ethanol-pretreated animals were anticipated to approach zero. Adults showed more rapid and sustained ethanol-induced hypothermia than adolescents. Acute tolerance to ethanol-induced hypothermia did not emerge clearly with the two-injection paradigm; ethanol-pretreated animals of both ages generally did not differ from those pretreated with water in their hypothermic response to ethanol despite higher BALs after the second intubation. Housing condition (paired or isolated) had little influence on ethanol-induced hypothermia. The adolescent attenuation of ethanol-induced hypothermia in this experiment was not associated with greater expression of within-session (acute) tolerance.

Age Factors↗

Evaluation of ambulatory cassette EEG monitoring: III. Diagnostic accuracy compared to intensive inpatient EEG monitoring.

We assessed the ability to recognize epileptiform abnormalities on a video review of ambulatory cassette EEGs (A/EEG) by comparing two independent interpretations of an A/EEG to those derived from a routine recording and intensive monitoring by cable telemetry (C/EEG) of the same 40 patients. Both A/EEG readings concurred with the C/EEG interpretation as to normality or epileptiform abnormality in 77% of cases. Seventy-nine percent of focal and 100% of generalized interictal abnormalities, as well as all seizures, noted on C/EEG were detected by both A/EEG reviewers. Of patients with normal baseline EEGs, 37% showed epileptiform features on A/EEG versus 44% with C/EEG. Limits to the characterization of abnormalities by A/EEG and a protocol for the video review of A/EEG tapes are discussed. In those specific areas for which intensive surface EEG monitoring is most useful, ambulatory cassette EEG appears to be an acceptable intermediate-level alternative.

Adolescent↗

Prolactin changes after seizures classified by EEG monitoring.

We examined the postictal hyperprolactinemia after seizures classified by EEG and video telemetry. Prolactin did rise after complex partial seizures that involved motor behaviors and was not further increased by secondary generalization. Nontemporal partial seizures or pseudoseizures did not demonstrate this increase. There was no difference in prolactin elevation after generalized tonic-clonic seizures, whether secondarily generalized or generalized from onset. A discriminant function accurately classified 94% of patients with pseudoseizures and 66% of patients with true cerebral seizures for an overall classification accuracy of 72%.

Adolescent↗

Ictal speech, postictal language dysfunction, and seizure lateralization.

In 84 patients with complex partial seizures evaluated by EEG and video telemetry, who went on to have seizure surgery, complex intraictal vocalizations and postictal language dysfunction were found to have strong lateralizing significance. Thirteen patients had ictal speech, and 12 of these had right-sided seizure foci. Twenty-eight had intact postictal language, and 21 of these had right-sided foci. Of the 32 with impaired postictal language, 21 had left-sided foci.

Electroencephalography↗

Increases in P-wave dispersion predict postoperative atrial fibrillation after coronary artery bypass graft surgery.

UNLABELLED: Atrial fibrillation (AF) is a common complication after coronary artery bypass graft (CABG) surgery. In this study we examined the effect of surgery on atrial electrophysiology as measured by P-wave characteristics and to determine the potential predictive value of P-wave characteristics on the incidences of postoperative AF in patients undergoing CABG surgery. Patients undergoing elective CABG surgery were monitored by continuous electrocardiogram (ECG) telemetry during the in-hospital period until discharge for the occurrence of postoperative AF. Differences in P-wave characteristics (P-wave duration, amplitude, axis, dispersion, PR interval, segment depression, and dispersion) were compared between the pre- and postoperative 12-lead ECG measurements, and also between patients with and without postoperative AF. The association of postoperative AF and potential clinical predictors and P-wave characteristics were determined by multivariate logistic regression. Postoperative AF occurred in 81 (27%) of 300 patients. Univariate analysis showed that patients who subsequently developed postoperative AF compared with those without AF were significantly older (mean age 68 +/- 8 versus 63 +/- 10 yr, P < 0.0001), had a larger body surface area (BSA) (2.03 +/- 0.24 versus 1.92 +/- 0.22 m(2), P = 0.0002), were more likely to have a history of AF (8 of 81 versus 1 of 219, P = 0.003), used preoperative antiarrhythmic medications more frequently (7 of 81 versus 4 of 219, P = 0.01), and had a more frequent rate of return to the operating room for postoperative complications (9 of 81 versus 9 of 219, P = 0.029). Furthermore, the postoperative P-wave duration decreased to a larger extent (mean change -11.3 +/- 0.1 ms versus -8.4 +/- 0.1 ms, P < 0.0001), and the P-wave dispersion increased postoperatively to a larger extent (3.1 +/- 15.5 ms versus -1.6 +/- 14.6 ms, P = 0.028) in those who subsequently developed AF compared with those without AF. Multivariate logistic regression showed age (odds ratio [OR] = 1.1, 95% confidence interval [CI]: 1.06-1.15, P < 0.0001), BSA (OR = 38.1, 95% CI: 8.2-176, P < 0.0001), and an increase in postoperative P-wave dispersion (OR = 1.03, 95% CI: 1.01-1.05, P = 0.01) to be independent predictors of postoperative AF. No surgical factor was identified to be responsible for this postoperative change in atrial electrophysiology. IMPLICATIONS: In addition to clinical factors, such as advanced age and body surface area, we demonstrated that electrophysiologic changes involving an increase in P-wave dispersion postoperatively independently predict atrial fibrillation after coronary artery bypass graft surgery.

Aged↗

Waved albatrosses can navigate with strong magnets attached to their head.

The foraging excursions of waved albatrosses Phoebastria irrorata during incubation are ideally suited for navigational studies because they navigate between their Galápagos breeding site and one specific foraging site in the upwelling zone of Peru along highly predictable, straight-line routes. We used satellite telemetry to follow free-flying albatrosses after manipulating magnetic orientation cues by attaching magnets to strategic places on the birds' heads. All experimental, sham-manipulated and control birds, were able to navigate back and forth from Galápagos to their normal foraging sites at the Peruvian coast over 1000 km away. Birds subjected to the three treatments did not differ in the routes flown or in the duration and speed of the trips. The interpretations and implications of this result depend on which of the current suggested magnetic sensory mechanisms is actually being used by the birds.

Animals↗

Determination of peak vertical ground reaction force from duty factor in the horse (Equus caballus).

Measurement of peak vertical ground reaction force (GRFz) from multiple limbs simultaneously during high-speed, over-ground locomotion would enhance our understanding of the locomotor mechanics of cursorial animals. Here, we evaluate the accuracy of predicting peak GRFz from duty factor (the proportion of the stride for which the limb is in contact with the ground). Foot-mounted uniaxial accelerometers, combined with UHF FM telemetry, are shown to be practical and accurate for the field measurement of stride timing variables, including duty factor. Direct comparison with the force plate produces a mean error of 2.3 ms and 3.5 ms for the timing of foot on and foot off, respectively, across all gaits. Predictions of peak GRFz from duty factor show mean errors (with positive values indicating an overestimate) of 0.8+/-0.04 N kg(-1) (13%; N=42; mean +/- S.E.M.) at walk, -0.3+/-0.06 N kg(-1) (3%; N=75) at trot, -2.3+/-0.27 N kg(-1) (16%; N=18) for the non-lead limb at canter and +2.1+/-0.7 N kg(-1) (19%; N=9) for the lead limb at canter. The substantial over- and underestimate seen at canter, in the lead and non-lead limbs, respectively, is attributed to the different functions performed by the two limbs in the asymmetrical gaits. The difference in load experienced by the lead and non-lead limbs decreased with increasing speed.

Acceleration↗