Aortic Depressor Nerve Activity Research Articles

The Hypo-Osmolality of Pregnancy Does Not Alter Baroreceptor Responses to Acute Changes in Osmolality

Reducing extracellular osmolality by 10-12 mOsm/L reduces baroreceptor firing in vitro in tissues from male rats. Pregnancy is associated with a similar reduction in plasma osmolality (pOsm) as well as with alterations in baroreceptor firing and reduced baroreceptor reflex activity. Mechanisms for reduced baroreflex activity are not yet understood, but they have important implications for maintenance of cardiovascular homeostasis in the pregnant female. Thus, this study was designed to test whether changes in plasma osmolality alter baroreceptor discharge during pregnancy. Late-gestation pregnant and virgin control rats were anesthetized, femoral vessels were cannulated for measurement of arterial pressure and drug infusion, and the aortic depressor nerve, containing baroreceptor afferents, was isolated and prepared for recording. Plasma osmolality was measured before and 30 min after graded intraperitoneal injections of NaCl (50-1500 mOsm/L). Arterial pressure, heart rate, and aortic depressor nerve activity (ADNA) were measured continuously before and after injections. A 50 mOsm/L NaCl injection significantly decreased pOsm but did not alter ADNA in either group. Likewise, 1200 mOsm/L NaCl injections significantly increased pOsm and had no effect on ADNA in either group. The 1500 mOsm salt load significantly increased pOsm and ADNA in pregnant rats, and in virgin animals, it increased pOsm but evoked a paradoxical decrease in ADNA. The authors' studies indicate that pOsm has minimal effects on baroreceptor activity, which are not significantly different during gestation. Their findings suggest that in vitro data from male rats indicating a correlation between pOsm and baroreceptor discharge are not applicable in anesthetized intact female animals.

Analysis of afferent, central, and efferent components of the baroreceptor reflex in mice.

Studies of genetically modified mice provide a powerful approach to investigate consequences of altered gene expression in physiological and pathological states. The goal of the present study was to characterize afferent, central, and efferent components of the baroreceptor reflex in anesthetized Webster 4 mice. Baroreflex and baroreceptor afferent functions were characterized by measuring changes in renal sympathetic nerve activity (RSNA) and aortic depressor nerve activity (ADNA) in response to nitroprusside- and phenylephrine-induced changes in arterial pressure. The data were fit to a sigmoidal logistic function curve. Baroreflex diastolic pressure threshold (P(th)), the pressure at 50% inhibition of RSNA (P(mid)), and baroreflex gain (maximum slope) averaged 74 +/- 5 mmHg, 101 +/- 3 mmHg, and 2.30 +/- 0.54%/mmHg, respectively (n = 6). The P(th), P(mid), and gain for the diastolic pressure-ADNA relation (baroreceptor afferents) were similar to that observed for the overall reflex averaging 79 +/- 9 mmHg, 101 +/- 4 mmHg, and 2.92 +/- 0.53%/mmHg, respectively (n = 5). The central nervous system mediation of the baroreflex and the chronotropic responsiveness of the heart to vagal efferent activity were independently assessed by recording responses to electrical stimulation of the left ADN and the peripheral end of the right vagus nerve, respectively. Both ADN and vagal efferent stimulation induced frequency-dependent decreases in heart rate and arterial pressure. The heart rate response to ADN stimulation was nearly abolished in mice anesthetized with pentobarbital sodium (n = 4) compared with mice anesthetized with ketamine-acepromazine (n = 4), whereas the response to vagal efferent stimulation was equivalent under both types of anesthesia. Application of these techniques to studies of genetically manipulated mice can be used to identify molecular mechanisms of baroreflex function and to localize altered function to afferent, central, or efferent sites.

Reflex control of arterial pressure and heart rate in short-term streptozotocin diabetic rats.

Impaired baroreflex sensitivity in diabetes is well described and has been attributed to autonomic diabetic neuropathy. In the present study conducted on acute (10-20 days) streptozotocin (STZ)-induced diabetic rats we examined: 1) cardiac baroreflex sensitivity, assessed by the slope of the linear regression between phenylephrine- or sodium nitroprusside-induced changes in arterial pressure and reflex changes in heart rate (HR) in conscious rats; 2) aortic baroreceptor function by means of the relationship between systolic arterial pressure and aortic depressor nerve (ADN) activity, in anesthetized rats, and 3) bradycardia produced by electrical stimulation of the vagus nerve or by the iv injection of methacholine in anesthetized animals. Reflex bradycardia (-1.4 +/- 0.1 vs -1.7 +/- 0.1 bpm/mmHg) and tachycardia (-2.1 +/- 0.3 vs -3.0 +/- 0.2 bpm/mmHg) were reduced in the diabetic group. The gain of the ADN activity relationship was similar in control (1.7 +/- 0.1% max/mmHg) and diabetic (1.5 +/- 0.1% max/mmHg) animals. The HR response to vagal nerve stimulation with 16, 32 and 64 Hz was 13, 16 and 14% higher, respectively, than the response of STZ-treated rats. The HR response to increasing doses of methacholine was also higher in the diabetic group compared to control animals. Our results confirm the baroreflex dysfunction detected in previous studies on short-term diabetic rats. Moreover, the normal baroreceptor function and the altered HR responses to vagal stimulation or methacholine injection suggest that the efferent limb of the baroreflex is mainly responsible for baroreflex dysfunction in this model of diabetes.

A novel photocurable insulator material for autonomic nerve activity recording

The two-component, addition-curing silicone glue is widely used as an insulator for autonomic nerve activity recording. Due to its high fluidity before curing, a sizable mass of the glue is needed to completely cover the electrode tips, which may cause mechanical stress on the nerve. To overcome this problem, we designed a novel photocurable insulator material composed of Vaseline and 1,12-dodecanediol diacrylate (50:50 wt%) together with a photoinitiator, camphorquinone, at 0.25 wt%. This material had an appropriate viscosity of 0.18 Pa s at 25°C and was converted to a soft solid upon an arbitrary timing of photoirradiation. The compressive force per mm deformation of the resulting solid was 155.5 kPa at 1 min of photoirradiation. The impedance of the solid for 1 mm length and 10 mm 2 cross-sectional area was above 1 MΩ. In anesthetized rabbits, a very small mass of the photocurable material was able to cover the electrode tips and the nerve in situ. Changes in both the aortic depressor nerve activity and renal sympathetic nerve activity were stably recorded. These results indicate that the photocurable material developed is useful as an in vivo insulator material for autonomic nerve activity recording.

Afferent baroreceptor discharge in pregnant rats.

The baroreflex function curve is shifted to lower operating pressures, efferent sympathoexcitatory responses are attenuated, and sympathoinhibitory responses are potentiated in pregnant compared with virgin rats. It has been proposed that during pregnancy, elevated levels of 3 alpha-hydroxy-dihydroprogesterone (3 alpha-OH-DHP), a major metabolite of progesterone, may contribute to this difference, because acute intravenous administration of 3 alpha-OH-DHP to virgin female rats mimics the effects of pregnancy on the baroreflex. To determine whether changes in the afferent limb might contribute to these baroreflex responses, the effects of pregnancy and 3 alpha-OH-DHP on aortic depressor nerve activity were assessed in the current study. Baroreceptor discharge curves were obtained in Inactin-anesthetized rats by recording aortic nerve activity during ramp increases and decreases in mean arterial pressure (MAP) [intravenous phenylephrine and nitroprusside infusion] before [(control, C) 15 min (E1), and 30 min (E2) after 3 alpha-OH-DHP (220 microg/kg bolus + 22 microg x kg(-1) x min(-1) infusion iv)]. Baseline blood pressure was significantly lower in pregnant (109 +/- 4.4 mmHg) compared with virgin (122 +/- 2.8 mmHg) rats. The only significant difference in the baroreceptor discharge curves was a decrease in curve midpoint in pregnant rats (virgin = 140 +/- 2.7 vs. pregnant = 124 +/- 3.6 mmHg). 3 alpha-OH-DHP had no effect on afferent baroreceptor discharge curves in either virgin or pregnant groups. These results suggest that pressure-dependent baroreceptor resetting may contribute to a shift in the baroreflex curve to lower operating pressures, but cannot completely explain differences in baroreflex function between virgin and pregnant animals.

Baroreceptor afferent discharge in the pregnant rat.

Pregnancy is associated with blunted reflex responses to cardiac and arterial baroreceptor stimulation. We tested the hypothesis that arterial baroreceptor afferent discharge is attenuated in response to a pressure stimulus in pregnant rats. Multifiber aortic depressor nerve activity (ADNA), mean arterial pressure (MAP), and heart rate were measured in anesthetized (pentobarbital sodium, 35 mg/kg ip) late-pregnant and virgin rats in response to increases ¿phenylephrine (PE), 1.5-24 microg. kg(-1). min(-1) and 1-16 microg/kg and decreases ¿sodium nitroprusside (SNP), 5-80 microg. kg(-1). min(-1) and 0.05-16 microg/kg in MAP. Resting MAP was lower in pregnant rats, but changes in MAP were similar to those in virgin rats during both PE and SNP administration. ADNA was significantly attenuated in pregnant animals during both PE and SNP infusions (P < 0.05) due to a more rapid adaptation to the pressure stimulus. Bolus drug administration evoked similar changes in MAP and ADNA in both groups; however, the maximum decrease in ADNA was achieved at the lowest dose of SNP in pregnant rats. Thus baroreceptor afferent discharge is attenuated in pregnant rats, and this involves a more rapid adaptation to a pressure stimulus.

Altered central nervous system processing of baroreceptor input following hindlimb unloading in rats.

The effect of cardiovascular deconditioning on central nervous system processing of baroreceptor afferent activity was evaluated following 14 days of hindlimb unloading (HU). Inactin-anesthetized rats were instrumented with catheters, renal sympathetic nerve electrodes, and aortic depressor nerve electrodes for measurement of mean arterial pressure, heart rate, renal sympathetic nerve activity (RSNA), and aortic depressor nerve activity (ADNA). Baroreceptor and baroreflex functions were assessed during infusion of phenylephrine and sodium nitroprusside. Central processing of baroreceptor afferent input was evaluated by linear regression relating RSNA to ADNA. The maximum baroreflex-elicited increase in RSNA was significantly reduced in HU rats (122 +/- 3.8 vs. 144 +/- 4.9% of baseline RSNA), whereas ADNA was not altered. The slope (-0.18 +/- 0.04 vs. -0.40 +/- 0.04) and y-intercept (121 +/- 3.2 vs. 146 +/- 4.3) of the linear regression relating increases in efferent RSNA to decreases in afferent ADNA during hypotension were significantly reduced in HU rats. There were no differences during increases in arterial pressure. Results demonstrate that the attenuation in baroreflex-mediated increases in RSNA following HU is due to changes in central processing of baroreceptor afferent information rather than aortic baroreceptor function.

Afferent and efferent nerve activity of arterial baroreceptor reflex under nonpulsatile systemic circulation.

We studied the changes in arterial baroreceptor reflex (ABR) afferent activity and efferent activity induced by nonpulsatile systemic circulation (NC) during total left heart bypass (TLHB) in rabbits. To evaluate the influence of the circuit priming fluid and exposure to NC, we directly measured aortic depressor nerve activity (ADNA) (n = 5) and renal sympathetic nerve activity (RSNA) (n = 5) before the start of partial left heart bypass (PLHB) (Before), after PHLB (After), and 5 min after the start of TLHB (During THLB) while maintaining the mean aortic pressure. The circuit priming fluid did not affect the ABR. ADNA exhibited periodic discharge at Before and After, but at During THLB, this periodic discharge transformed into a continuous discharge, and ADNA increased significantly. However, there were no significant differences in RSNA. Our results suggested that in the acute phase under NC, the ABR differed from that under natural circulation.

New simple methods for isolating baroreceptor regions of carotid sinus and aortic depressor nerves in rats.

We developed new methods for isolating in situ baroreceptor regions of carotid sinus and aortic depressor nerves in halothane-anesthetized rats. After ligation of the root of the external carotid artery, the internal carotid and pterygopalatine arteries were embolized with two ball bearings of 0.8 mm in diameter. Bilateral carotid sinus pressures were changed between 60 and 180 mmHg in 20-mmHg steps lasting 1 min each. The sigmoidal steady-state relationship between aortic and carotid sinus pressures in 11 rats indicated the maximum gain of the carotid sinus baroreflex to be -2. 99 +/- 0.75 at 120 +/- 5 mmHg. An in situ isolation of the baroreceptor area of the right aortic depressor nerve could be made by ligation of the innominate, common carotid, and subclavian arteries in 9 rats. Pressure imposed on the subclavian baroreceptor was altered between 40 and 180 mmHg in 20-mmHg steps lasting 1 min each. The sigmoidal steady-state relationship between the aortic depressor nerve activity and imposed pressure showed that the baroreceptor gain peaked at 118 +/- 4 mmHg. We established an easy approach to the rat baroreflex and baroreceptor research.

Arterial baroreceptor afferent activity in nonpulsatile systemic circulation.

We directly measured aortic depressor nerve activity (ADNA) in rabbits to investigate changes in arterial baroreceptor afferent activity (ABAA) in response to nonpulsatile systemic circulation (NC) during total left heart bypass (TLHB). ADNA was measured before and 5, 20, 30, 40, 50, and 60 min after the start of TLHB while maintaining the mean aortic pressure (MAP) at preestablished values (n=10). At 5 min, the ADNA was significantly increased compared to its baseline value. At 30 min, it was significantly decreased compared to its value at 5 min and thereafter remained the same. The ADNA was then measured before and 5 and 30 min after the start of TLHB under increased MAP (n=10). The results showed that the percentage changes in ADNA during TLHB were significantly less than that observed when the MAP was increased before TLHB. We conclude that ABAA acutely adapts to NC 30 min after its initiation, but changes in ABAA are depressed under NC combined with increased MAP.

Nonuniform sympathetic nerve responses after sustained elevation in arterial pressure.

We tested the hypothesis that sustained increases in mean arterial pressure (MAP) produce nonuniform changes in regional sympathetic nerve discharges (SND) after the return of MAP to control levels. Renal, adrenal, splanchnic, and lumbar SND were recorded before, during, and after a 30-min elevation in MAP produced by phenylephrine (PE) infusion in alpha-chloralose-anesthetized spontaneously hypertensive (SH) rats. SND remained reduced from control values after PE infusion, despite the return of MAP to control levels. Importantly, the duration of poststimulus sympathoinhibition was significantly less in adrenal and splanchnic SND compared with renal and lumbar SND. In sinoaortic-denervated SH rats, SND remained at control levels during and after PE infusion. Simultaneous recordings of aortic depressor nerve (ADN) activity and SND demonstrated that prolonged renal and lumbar sympathoinhibition occurred even when ADN activity fell below control levels after PE infusion. We conclude that poststimulus responses of efferent SND in SH rats are regionally nonuniform and that renal and lumbar sympathoinhibitory responses are not mediated solely by prolonged increases in afferent baroreceptor nerve activity.

Sustained increases in aortic depressor nerve activity after acute elevation in arterial pressure

Despite the return of mean arterial pressure (MAP) to control levels, aortic depressor nerve activity remains elevated from control levels after sustained phenylephrine-induced increases in MAP in spontaneously hypertensive rats (SHR) (Kenney MJ, Morgan DA, Mark AL: Am J Physiol 1990, 258:H1476-H1481). This suggests that sustained increases in arterial pressure may produce prolonged pressure-induced changes in afferent baroreceptor nerve activity in SHR. However, because phenylephrine can exert an excitatory effect on the aortic arch baroreceptors, the increase in aortic depressor nerve activity might have resulted from a persistent direct effect of phenylephrine. The aim of the current study was to determine whether elevations in MAP induced by aortic occlusion produce increases in aortic depressor nerve activity which persist after the return of MAP to control levels. MAP and aortic depressor nerve activity were recorded before, during and after sustained (15-30 min) periods of aortic occlusion in SHR with intact adrenal glands (n = 18) and in adrenalectomized SHR (n = 10). Control experiments were completed in which the same variables were recorded before, during and after sham aortic occlusion in intact (n = 8) and adrenalectomized (n = 8) SHR. Aortic occlusion increased MAP and aortic depressor nerve activity significantly from control levels. After aortic occlusion and the return of MAP to control levels, aortic depressor nerve activity remained significantly increased in 15 experiments, whereas in three experiments aortic depressor nerve activity was reduced. Aortic depressor nerve activity was increased significantly from control levels after aortic occlusion in adrenalectomized rats. Aortic depressor nerve activity remained unchanged from control levels after sham aortic occlusion in intact and adrenalectomized SHR. Sustained elevations in MAP induce increases in aortic depressor nerve activity in intact and adrenalectomized SHR, which persist after the return of MAP to control levels. These observations suggest that sustained increases in arterial pressure may produce prolonged pressure-induced changes in afferent baroreceptor nerve activity in SHR.

Hemodynamics and baroreflex function in rats with nephrotic syndrome

The excess renal sodium retention leading to edema formation in the nephrotic syndrome (NS) is substantially dependent on increased efferent renal sympathetic nerve activity (RSNA). This study examined whether the hypoalbuminemia in NS is reflected as a decrease in cardiac output or cardiac function and whether the increased RSNA in NS is due to alterations in arterial and/or cardiopulmonary baroreflex function. NS was induced in rats with adriamycin (3.5 mg/kg i.v.), and they were studied 4 wk after injection. Mean arterial pressure (MAP) was similar in control (C) and NS rats. Cardiac indexes (CIs; cardiac output/body wt) were 29 +/- 1 and 26 +/- 1 ml.min-1.100 g-1 in C and NS rats, respectively. Total peripheral resistance indexes were significantly greater in NS than in C rats (4.7 +/- 0.2 vs. 4.1 +/- 0.1 mmHg.100 g.min.ml-1). Cardiac function during increases in cardiac filling pressure was not different between C and NS rats. The afferent limb of the arterial baroreflex was assessed by measuring aortic depressor nerve activity (ADNA) while the efferent limb was assessed by measuring RSNA in C and NS rats during increases in MAP. The central component of the arterial baroreflex was assessed from plots of RSNA (output) vs. ADNA (input). Comparisons between C and NS rats before and after vagotomy revealed no differences in the gains of any component of the arterial baroreflex. The cardiopulmonary baroreflex was assessed in a similar manner by measuring afferent vagus nerve activity (VGNA) and efferent RSNA during volume expansion before and after sinoaortic denervation (SAD). Before SAD, gains were similar in C and NS rats. After SAD, gains of the total (-1.59 +/- 0.44 vs. -3.64 +/- 0.65%/mmHg) and the central/efferent limb (-0.26 +/- 0.07 vs. -0.67 +/- 0.14 %/%) were significantly reduced (P < 0.05) in NS compared with C rats while the gain of the afferent limb of the reflex was similar in C and NS rats. These results indicate that NS rats with significant hypoalbuminemia maintain an arterial pressure similar to C rats by increasing total peripheral resistance, which serves to offset the tendency to a lower CI. Arterial baroreflex function in NS does not differ from that in C, but decreased cardiopulmonary baroreflex inhibition of RSNA in NS may contribute to the increased RSNA.

Transfer function analysis from arterial baroreceptor afferent activity to renal nerve activity in rabbits

In vagotomized and anesthetized rabbits, aortic pressure (AP), aortic depressor nerve activity (ANA), and renal sympathetic nerve activity (RNA) were simultaneously measured while perturbing AP randomly. To quantitatively characterize the role of the arterial baroreflex system in generating RNA, we determined the transfer function (TF) of the central baroreflex arc from ANA to RNA in the frequency domain (0.02-5 Hz). The magnitude of squared coherence was > 0.5, the phase was close to -180 degrees, and the gain of TF was flat over 0.02-0.3 Hz, indicating that changes in RNA were linearly and instantaneously but inversely related to changes in ANA over this frequency range. Above 0.3 Hz, the coherence was low, suggesting that RNA unrelated to ANA existed in the frequency range. In animals without AP perturbations, power spectrum of RNA resided over 0.2-5 Hz with a broad peak at 1 Hz, which may represent central activity. Our results suggest that over 0.02-0.3 Hz the relationship between arterial baroreceptor afferent nerve activity and RNA is linear and instantaneous but above 0.3 Hz it is not linear possibly due to an interaction between central activity and arterial baroreflex.

Contribution of wall mechanics to the dynamic properties of aortic baroreceptors.

To examine the contribution of wall mechanics to dynamic properties of baroreceptors, we subdivided the transfer function of baroreceptors into two subsystems [aortic pressure to diameter and diameter to aortic depressor nerve activity (ANA)]. In six alpha-chloralose-anesthetized rabbits, we measured pressure, diameter, and ANA while randomly perturbing pressure. We obtained transfer functions (pressure to ANA, diameter to ANA, and pressure to diameter) by taking the ratio of crosspower spectrum to the input power spectrum (0.005-5 Hz). Below 3 Hz, the transfer function from pressure to ANA was nearly identical to that from diameter to ANA, whereas that from pressure to diameter was flat. Using transfer functions we could reproduce adaptation and hysteresis that were quantitatively similar between pressure-ANA transduction and diameter-ANA transduction. The pressure-diameter relationship was almost instantaneous and thus showed no hysteresis. In a second group of rabbits, the ratio of the shift of the hysteresis loop was unchanged by ouabain (40 micrograms/kg iv, n = 7). We conclude that the dynamic properties of baroreceptors may not be related to the wall mechanics or the Na(+)-K(+)-adenosinetriphosphatase activity.

The Anti-Tachycardic Mechanism of a Direct-Acting Vasodilator, Budralazine, in Rats

The present study was undertaken to elucidate the anti-tachycardic effect of a direct-acting vasodilator, budralazine, using an electrophysiological technique. Normotensive male Wistar rats were used. Rats were anesthetized intraperitoneally with urethane and alpha-chloralose. Intravenous administration of budralazine (0.5-5.0 mg/kg) produced a dose-dependent reduction of mean arterial pressure in anesthetized rats. At doses of 0.5 and 1.0 mg/kg, budralazine induced bradycardia accompanied with a decrease in cardiac sympathetic nerve activity (ICNA). Preganglionic adrenal sympathetic nerve activity (ASNA) was also reduced by budralazine (1.0 mg/kg). A 0.5 mg/kg of budralazine neither influenced carotid sinus nerve activity nor augmented aortic depressor nerve activity (ADNA). On the contrary, at dose of 5.0 mg/kg, budralazine produced a tachycardia accompanied with increases in both ICNA and ASNA. The ADNA was decreased by budralazine (5.0 mg/kg) significantly. These findings suggest that the central sympathoinhibitory action of budralazine may be responsible for the anti-tachycardic effect of budralazine and baroreceptor-mediated tachycardia occurred after high dose of budralazine.

Prolonged renal sympathoinhibition following sustained elevation in arterial pressure

We tested the hypothesis that sustained elevations in mean arterial pressure (MAP) would produce an abbreviated suppression of renal sympathetic nerve activity (RSNA) in spontaneously hypertensive (SH) compared with Wistar-Kyoto (WKY) normotensive rats. For this purpose, we recorded RSNA during and after a 30-min elevation in MAP. Elevations in MAP (35-40 mmHg) induced by phenylephrine resulted in a suppression of RSNA in SH and WKY rats that persisted after MAP had returned to control levels. The prolonged suppression of RSNA was eliminated following sinoaortic denervation, indicating that this response was dependent on afferent baroreceptor mechanisms. The simultaneous recording of RSNA and aortic depressor nerve (ADN) activity provided additional evidence that baroreceptor afferents contribute to this prolonged suppression of RSNA in SH rats. Despite the return of MAP to control levels following the sustained pressure elevation in SH rats, there was a paradoxical increase in ADN activity (39 +/- 14%) compared with control values. In contrast, both ADN activity and MAP returned to control levels in WKY rats following the sustained pressure elevation. The sustained increase of ADN activity in SH rats did not account for the entire magnitude of the prolonged recovery of RSNA. In summary, both SH and WKY rats exhibit prolonged suppression of RSNA, whereas ADN activity is paradoxically elevated in only SH rats following a sustained elevation in MAP.

A new method to identify dynamic transduction properties of aortic baroreceptors

We identified, in 17 alpha-chloralose-anesthetized rabbits, the dynamic transduction characteristics of the aortic arch baroreceptors using a "white-noise technique." We recorded aortic pressure and aortic depressor nerve activity while perturbing pressure by rapid, intermittent ventricular pacing (400 beats/min). Dividing the cross-power spectrum between nerve activity and pressure by the power spectrum of pressure yielded the transfer function. The gain of the transfer function increased threefold as the frequency increased from 0.005 to 5 Hz, suggesting that the baroreceptors responded primarily to dynamic rather than to static changes in pressure. To quantify the nonlinear properties of baroreceptor transduction, we compared measured instantaneous nerve activity with that linearly predicted. We demonstrated that the major nonlinearity was attributable to "threshold". The overall baroreceptor transduction properties could be represented by a cascade connection of a linear subsystem followed by a nonlinear subsystem with threshold. The white-noise technique made it possible to identify the unbiased linear properties in a nonlinear system, and thus was very useful in identifying complex biological systems.

Central Sympathoinhibitory Action of a Direct-Acting Vasodilator, Budralazine, in Anesthetized Rats

Previous data on budralazine, 1-[2-(1,3-dimethyl-2-butenylidene)-hydrazino]-phthalazine, has indicated that it is a direct-acting vasodilating agent that does not produce marked tachycardia. The present study was undertaken to elucidate what effects may be seen on the central sympathetic nerve activity when budralazine is given systemically to rats. Budralazine (0.5, 1.0 and 5.0 mg/kg, i. v.) produced a dose-dependent reduction of mean arterial pressure. At doses of 0.5 and 1.0 mg/kg, budralazine induced bradycardia accompanied with a decrease in cardiac sympathetic nerve activity. Preganglionic adrenal sympathetic nerve activity was also reduced by budralazine (1.0 mg/kg, i.v.). A dose of 0.5 mg/kg of budralazine neither influenced carotid sinus nerve activity nor augmented aortic depressor nerve activity. On the contrary, a high dose of budralazine (5.0 mg/kg) produced simultaneous increases in the heart rate and cardiac sympathetic nerve activity along with a marked suppression of aortic depressor nerve activity. Plasma norepinephrine and epinephrine concentrations were also increased at a dose of 5.0 mg/kg. These findings suggest that budralazine doses of 0.5 and 1.0 mg/kg may reduce the sympathetic outflow that is mediated via central sympathoinhibitory action. Baroreceptor-mediated tachycardia occurred after high dose budralazine (5.0 mg/kg) administration in anesthetized rats.

Rapid resetting of aortic nerves in conscious rabbits.

The effect of increased arterial pressure on aortic depressor nerve activity was studied in the conscious rabbit. Aortic baroreceptor resetting was observed following 15 min of sustained pressure elevation. At 15 min, there was a significant increase in the threshold arterial pressure for aortic nerve activity, but peak nerve activity did not change. This resulted in an increase in the slope of the pressure-nerve activity relationship. Therefore, except for peak nerve activity, aortic nerve activity was reduced at all pressures following 15 min of sustained pressure elevation. At 30 min, peak nerve activity also increased, resulting in a parallel shift in the pressure-activity curve. The early increase in slope of the pressure-activity relationship may be due to an early resetting of low threshold fibers with a high pressure differential between their threshold pressure and the sustained pressure elevation used to induce resetting. A late resetting of high threshold fibers with a low pressure differential between their threshold pressures and the pressure used to cause resetting of baroreceptors results in a parallel shift in the curve observed at 30 min. These data obtained from multiunit recordings provide unexpected evidence about baroreceptor resetting, which is not apparent from single-unit recordings.