Biomedical subjects

M W Chapleau

Publications and source records attributed to M W Chapleau.

54 records · Page 3Linked to original sources

PubMed1991

Paracrine role of prostanoids in activation of arterial baroreceptors: an overview.

Baroreceptors located in carotid sinuses and aortic arch are activated with increases in arterial pressure. The increased afferent nerve activity triggers reflex adjustments that buffer the rise in pressure. Mechanical deformation of baroreceptor nerve endings is considered the primary mechanism of receptor activation. Recent studies in our laboratory have demonstrated that prostanoids, most likely released from endothelial cells during stretch, contribute--as paracrine factors--to the activation of baroreceptors. Exposure of the isolated carotid sinus in anesthetized rabbits to prostacyclin (PGI2) or arachidonic acid increases baroreceptor sensitivity whereas inhibition of endogenous formation of prostanoids with indomethacin or aspirin decreases sensitivity. Baroreceptor sensitivity is also decreased after endothelial denudation and restored after adding PGI2 back to the denuded sinus suggesting that endothelium is the source of prostanoids that sensitize baroreceptors. Pathologic states such as chronic hypertension and atherosclerosis are associated with both endothelial cell dysfunction and decreased baroreceptor sensitivity. The endothelial cell dysfunction and impairment of prostanoid formation contribute to the decreased baroreceptor sensitivity in these diseases.

Animals↗

PubMed1990

Prostaglandins contribute to activation of baroreceptors in rabbits. Possible paracrine influence of endothelium.

The purpose of this study was to test the hypothesis that prostaglandins released from vascular endothelial cells contribute to activation of baroreceptors during increases in arterial pressure. Baroreceptor activity was recorded from the vascularly isolated carotid sinus in rabbits anesthetized with chloralose. Baroreceptor activity was measured during ramp or step increases in nonpulsatile carotid sinus pressure over a range of 0-175 mm Hg. Exposure of the isolated carotid sinus to inhibitors of prostaglandin formation (indomethacin [n = 10] or aspirin [n = 6]) decreased baroreceptor activity significantly (p less than 0.05). The slope of the pressure-activity relation averaged 0.80 +/- 0.07 %/mm Hg (mean +/- SEM) during control measurements and 0.72 +/- 0.06 and 0.63 +/- 0.05 %/mm Hg during exposure to 10 and 20 microM indomethacin, respectively. Exposure of the carotid sinus to exogenous prostacyclin (PGI2 [n = 11]) increased baroreceptor activity significantly. The slope of the pressure-activity relation averaged 0.89 +/- 0.10, 1.09 +/- 0.09, and 1.26 +/- 0.16 %/mm Hg during control and during exposure to 10 and 20 microM PGI2, respectively. Activity returned to control after removal of PGI2 (0.89 +/- 0.12 %/mm Hg). Removal of endothelium with either a balloon catheter (n = 4) or a jet of a 95% O2-5% CO2 gas mixture (n = 6) decreased the slope of the pressure-activity relation from 0.92 +/- 0.09 to 0.56 +/- 0.08 %/mm Hg (p less than 0.05). Exposure of the denuded sinus to exogenous PGI2 (20 microM [n = 4]) restored activity (slope = 1.09 +/- 0.24 %/mm Hg). Neither indomethacin (n = 5) nor PGI2 (n = 5) nor denudation (n = 5) significantly altered the pressure-diameter relation of the carotid sinus (sonomicrometers), suggesting that the effects on baroreceptor discharge are not caused by altered stretch of the carotid sinus at a given pressure. The results suggest that prostaglandins (e.g., PGI2) released from endothelium contribute in a paracrine manner to activation of baroreceptors during increases in arterial pressure.

Animals↗

PubMed1990

Mechanism of decreased baroreceptor activity in chronic hypertensive rabbits. Role of endogenous prostanoids.

We examined the contribution of endogenous prostanoids to baroreceptor activation in chronic renal hypertension. Baroreceptor activity was recorded from the vascularly isolated carotid sinus during slow ramp increases in pressure in rabbits anesthetized with pentothal and chloralose. Mean arterial pressure averaged 133 +/- 4 mmHg in hypertensive rabbits (one kidney, one wrap, n = 12) and 85 +/- 3 mmHg in normotensive rabbits (one kidney, no wrap, n = 13). Baroreceptor activity was decreased significantly (P less than 0.05) in the hypertensive compared with the normotensive rabbits. The decreased baroreceptor activity could not be explained by decreased distensibility of the carotid sinus (sonomicrometers). Inhibition of the endogenous formation of prostanoids with intrasinus administration of indomethacin (50 microM) decreased baroreceptor activity in normotensive (P less than 0.05) but not in hypertensive rabbits over a wide range of pressures. At a pressure of 120 mmHg, activity declined from 61 +/- 14 spikes/s before indomethacin to 47 +/- 12 spikes/s with indomethacin, i.e., a drop of 24 +/- 4%. In contrast, corresponding values in hypertensive rabbits averaged 41 +/- 13 and 40 +/- 12 spikes/s (-1 +/- 2%). Intrasinus prostacyclin, on the other hand, increased activity in both groups: at 120 mmHg activity increased from 62 +/- 9 to 92 +/- 15 spikes/s (51 +/- 17%) in normotensive rabbits and from 29+/- 7 to 47 +/- 14 spikes/s (68 +/- 23%) in hypertensive rabbits. Neither indomethacin nor prostacyclin (n = 5) influenced the pressure-diameter relation of the carotid sinus. The increase in prostacyclin (6-keto-PGF 1 alpha) formation by the sinus in response to its exposure to arachidonic acid (10 microM) was significant (P less than 0.05) in the normotensives (1,627 +/- 344%; n = 5) but not in the hypertensives (583 +/- 353%; n = 5). We conclude that the decreased baroreceptor activity in chronic hypertension may not be caused by decreased distensibility of the vascular wall of the sinus and that endogenous prostanoids that contribute to baroreceptor activation in normotensive rabbits fail to do so in hypertensive rabbits. This appears to be due to decreased formation of prostacyclin rather than decreased sensitivity of the baroreceptors to prostacyclin. The results suggest a new mechanism that contributes to chronic baroreceptor resetting in hypertension.

Animals↗

PubMed1989

Peripheral and central mechanisms of baroreflex resetting.

1. A change in the arterial pressure-sympathetic activity or heart rate relation (baroreflex resetting) can result from resetting of baroreceptors ('peripheral' resetting) or from an altered coupling within the central nervous system of afferent baroreceptor to efferent nerve activities ('central' resetting). 2. 'Peripheral' resetting involves a shift in the pressure-baroreceptor activity curve in the direction of the prevailing level of arterial pressure, e.g. after elevations in pressure, the baroreceptor pressure threshold (Pth) is increased and activity reduced at equivalent pressures and vascular strains. 3. 'Peripheral' resetting occurs during the diastolic phase of a cardiac cycle (instantaneous resetting), after brief exposure to elevated pressure (acute resetting), and during chronic hypertension or when chronic structural changes in the vasculature have occurred (chronic resetting). 4. Mechanisms include: (i) changes in the mechanical properties of the vessel wall that may alter the tension on the receptors; (ii) ionic mechanisms operating at the neuronal membrane such as activation of Na+,K+-ATPase; and (iii) release of endothelial factors that may modulate baroreceptor sensitivity. 5. Acute resetting of baroreceptors can be prevented or attenuated when the sustained elevations in pressure are pulsatile rather than static. Increases in flow increase carotid sinus nerve activity at constant pressure and strain and decrease the Pth of baroreceptors. 6. 'Central' resetting can involve neural-humoral interactions or an altered responsiveness of central neurons mediating the baroreflex to changes in afferent baroreceptor activity. 7. During static pressure, the continuous baroreceptor discharge causes significant 'central' resetting, i.e. sympathetic activity escapes from baroreflex inhibition. In contrast, during pulsatile pressure, the pulse phasic baroreceptor discharge minimizes 'central' resetting causing sustained sympathetic inhibition.

Animals↗

PubMed1989

Pulsatile activation of baroreceptors causes central facilitation of baroreflex.

The reflex decrease in arterial pressure is greater and more sustained with elevated pulsatile than with elevated static carotid sinus pressure. The purpose of this study was to relate afferent baroreceptor activity (BRA) and efferent sympathetic nerve activity (SNA) during static and pulsatile pressure to evaluate the influence of pulsatile pressure on the central mediation of the baroreflex. The carotid sinuses were isolated in 11 dogs anesthetized with chloralose. Both vagosympathetic trunks were cut and both carotid sinuses exposed to static and pulsatile pressures over a range of mean carotid sinus pressures (40-180 mmHg). BRA was recorded from one carotid sinus nerve, and the other intact carotid sinus served to initiate reflex changes in lumbar or renal SNA and arterial pressure. For the same mean carotid sinus pressure, pulsatile pressure caused significantly greater inhibition of SNA than static pressure. More importantly, for the same or lesser levels of baroreceptor activity per second, pulsatile pressure caused significantly greater inhibition of SNA than static pressure. The inhibition of SNA was not sustained (i.e., there was "adaptation") with continuous baroreceptor input during static pressure, whereas the inhibition of SNA was sustained (i.e., there was no significant adaptation) with the phasic input during pulsatile pressure. Increases in pulse frequency from 1.4 to 2.5 and 3.7 Hz caused progressively less inhibition of SNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Prostaglandins in carotid sinus enhance baroreflex in rabbits.

The purpose of this study was to examine the possible influence of endogenous prostaglandins in the carotid sinus on the arterial baroreflex. Lumbar sympathetic nerve activity (LSNA) and arterial pressure were recorded during step increases in isolated carotid sinus pressure in rabbits anesthetized with chloralose. Baroreflex responses were facilitated after intrasinus administration of prostacyclin (PGI2; 5 and 10 microM, n = 6) or arachidonic acid (10 microM, n = 12). PGI2 (10 microM) increased the slope of the carotid sinus pressure-LSNA relation (gain) from -0.32 +/- 0.09 to -1.19 +/- 0.38 spikes.s-1.mmHg-1 and decreased the pressure at which 50% of the maximum inhibition of LSNA occurred (EP50) from 127 +/- 5 to 98 +/- 4 mmHg (P less than 0.05). Similar responses were observed with arachidonic acid. Baroreflex responses were attenuated after intrasinus administration of indomethacin (40 and 80 microM, n = 5) or aspirin (1 and 2 mM, n = 7). Indomethacin (80 microM) decreased the gain of the baroreflex from -1.02 +/- 0.24 to -0.47 +/- 0.16 spikes.s-1.mmHg-1 and increased the EP50 from 121 +/- 6 to 133 +/- 7 mmHg (P less than 0.05). Both indomethacin (80 microM) and aspirin (2 mM) reduced the maximum percent inhibition of LSNA significantly. The results indicate that prostaglandins within the carotid sinus facilitate the baroreflex control of LSNA. The attenuation of the baroreflex after inhibition of cyclooxygenase suggests that endogenous prostaglandins contribute to the activation of baroreceptors during increases in carotid sinus pressure.

Animals↗

PubMed1989

Determinants of sensitization of carotid baroreceptors by pulsatile pressure in dogs.

The threshold pressure of single baroreceptor units is decreased after compared with before exposure to pulsatile pressure according to previous studies in our laboratory. The purpose of the present study is to characterize the determinants of sensitization of arterial baroreceptors by pulsatile pressure. Carotid sinus nerve activity was recorded in dogs anesthetized with chloralose. Two indexes of baroreceptor "sensitivity" were obtained by comparing nerve activity before and immediately after exposure of the isolated carotid sinus to pulsatile pressure for periods up to 10 minutes. Sensitization occurred 1) when the threshold pressure of single baroreceptor units determined with a slow nonpulsatile ramp decreased after as compared with before pulsing and 2) when multiple unit activity increased after as compared with before pulsing at various mean levels of static pressure. Sensitization was evident after pulsing at mean pressure of 50 and 100 mm Hg, but not at 150 and 200 mm Hg, and was caused by the pulsatile change in diameter or deformation and not by the pulsatile change in wall tension. The magnitude of the effect was directly related to the duration of the pulsing period and to the frequency and amplitude of the pressure pulses. The sensitization could not be explained by increased diameter (sonomicrometers) or strain of the carotid sinus at the same pressure after pulsing; thus, there was an increase in "strain sensitivity" that outlasted the period of pulsing by up to several minutes. In most experiments the shift from static to pulsatile pressure at 50 and 100 mm Hg caused an increase in nerve activity, yet sensitization occurred after pulsing when one would have expected postexcitatory hyperpolarization or depression of activity upon return to static pressure. The sensitization was not caused by the release of prostacyclin from the endothelium since it was not reduced after endothelial denudation or inhibition of cyclooxygenase with indomethacin (30-80 microM) or ibuprofen (250 microM). We speculate that sensitization of baroreceptors by pulsatile pressure may contribute to the decreased sympathetic activity after periods of elevated pulse pressure (e.g., after exercise). We also propose that the decreased sensitivity of baroreceptors after acute elevation of arterial pressure (acute resetting) may be offset in part by the sensitizing effect of increased pulsatile stretch.

Animals↗

PubMed1988

Chemoreceptor stimulation interferes with regional hypoxic pulmonary vasoconstriction.

Hypoxemia interferes with the diversion of blood flow away from hypoxic regions of the lung, possibly through activation of the arterial chemoreceptor reflex. The purpose of this study was to determine if selective stimulation of carotid chemoreceptors reduces the diversion of flow (hypoxic vasoconstriction) when normal systemic oxygen levels are present. Chloralose anesthetized dogs were paralyzed and each lung was separately ventilated via a dual-lumen endobronchial tube. Left pulmonary artery (QL) and main pulmonary artery (QT) blood flows were measured with electromagnetic flow probes. Chemoreceptors were stimulated by perfusion of the carotid sinuses with hypoxic, hypercapnic blood. QL/QT averaged 46 +/- 4, 29 +/- 2, and 36 +/- 4% during bilateral O2 ventilation (control), left lung N2 ventilation, and left lung N2 plus chemoreceptor stimulation in dogs treated with the cyclo-oxygenase inhibitor meclofenamate. After vagotomy, QL/QT averaged 45 +/- 4, 27 +/- 3, and 28 +/- 2% during the same conditions. QL/QT decreased significantly from control (P less than 0.05) during left lung N2 alone but did not decrease during left lung N2 plus chemoreceptor stimulation in dogs with intact vagi. In contrast, QL/QT decreased significantly both before and during chemoreceptor stimulation in vagotomized dogs. The same responses were observed in dogs not treated with meclofenamate. These results indicate that selective stimulation of arterial chemoreceptors can interfere with regional hypoxic vasoconstriction and suggest that the vagus nerves may mediate this effect.

Animals↗

PubMed1988

Rheoreceptors in the carotid sinus of dog.

The arterial baroreceptors are known to be sensitive to changes in pressure but there are no known sensors in the cardiovascular system for changes in flow. We tested the hypothesis that changes in flow at constant pressure alter carotid sinus multi-unit nerve activity. In anesthetized dogs with vascularly isolated carotid sinuses, increases in flow at constant pressure resulted in increases in carotid sinus nerve activity in relation to the increase in flow. The increased activity during flow was not caused by an increase in strain of the sinus wall but was directly related to the increase in shear stress (36.6 +/- 11.7% increase in activity per dyne/cm2; 1 dyne = 0.1 MN). The pressure threshold of single baroreceptor units was determined during a slow pressure ramp with and without flow. Flow caused a significant decrease in pressure threshold from 81.1 +/- 6.1 mmHg (1 mmHg = 1.333 x 10(2) Pa) in the absence of flow to 69.3 +/- 5.7 mmHg with flow. We conclude that there are arterial "rheoreceptors" in the carotid sinus that respond to flow at constant pressure and strain. The results with single baroreceptor units indicate also that baroreceptors may be sensitized by increases in flow. Thus, changes in flow per se in addition to changes in arterial pressure may be important determinants of reflex circulatory adjustments.

Animals↗

PubMed1988

Mechanisms of resetting of arterial baroreceptors: an overview.

Arterial baroreceptors are reset when their afferent nerve activity is reduced at an equivalent arterial pressure and vascular strain. Resetting occurs as a result of stretch of the baroreceptors, usually during an acute or chronic rise in arterial pressure. It may be seen during the diastolic phase of a cardiac cycle (instantaneous resetting), after brief exposure to a sustained elevation of pressure (acute resetting), and after chronic elevation of pressure or in physiologic or pathologic states associated with structural changes in the vascular regions of baroreceptors (chronic resetting). The mechanisms reviewed here include mechanical, ionic and chemical factors. Viscoelastic properties of the carotid sinus and aortic arch may explain the instantaneous resetting that occurs with each cardiac cycle when activity begins in early systole and stops in early diastole. Viscoelastic properties and ionic mechanisms may play a role in acute resetting. Inhibition of Na+K+ ATPase reduces the magnitude of acute resetting. The release of chemicals from the endothelium may modulate baroreceptor activity. Exogenous prostacyclin suppresses and indomethacin augments acute resetting in the rabbit, suggesting that the release of endogenous prostacyclin during a rise in arterial pressure attenuates resetting. Changes in pulsatility and blood flow also may modulate baroreceptor activity. The addition of pulsatile pressure at an increased mean pressure attenuates resetting.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Effects of pulse frequency on single-unit baroreceptor activity during sine-wave and natural pulses in dogs.

1. Previous studies using sine-wave pulses have shown that changes in pulse frequency do not alter single-unit activity per unit time. Since baroreceptor activity is phasic with most of the activity occurring in systole, we reasoned that the lack of effect of pulse frequency is due to the associated reciprocal change in duration of systole with sine-wave pulses. Therefore, we tested the hypothesis that change in frequency using natural arterial pulses alters baroreceptor unit activity per unit time. 2. In chloralose-anaesthetized dogs the isolated carotid sinus was connected to an electromagnetic pressure converter driven by a voltage generator that controlled pulse pressure and sine-wave pulse rate. To generate a natural pulse the converter was driven by the output from the pressure channel used to record arterial pressure. Systolic and diastolic pressures were maintained constant by a pressurized air source and an adjustable control on the voltage generator. The rate of natural pulses was decreased by electrical stimulation of the peripheral right vagus nerve which slowed the heart rate of the dog. 3. Decreases in sine-wave rate by approximately 73 pulses/min (from 156 +/- 2 to 83 +/- 1 pulses/min) at a mean pressure of 114 +/- 8 mmHg (n = 13) did not alter activity per unit time (28 +/- 3 vs. 29 +/- 3 spikes/s). 4. In contrast, decreases in natural pulse rate by an average of 78 pulses/min (from 182 +/- 7 to 104 +/- 15 pulses/min) at a comparable mean pressure (104 +/- 7 mmHg) (n = 9) decreased activity per unit time by 28% from 32 +/- 4 to 23 +/- 4 spikes/s (P less than 0.05). Similar findings were observed in five of six single units using an intact (normally perfused) carotid sinus preparation in dogs with heart block and cardiac pacing. 5. The results indicate that a change in natural pulse rate is an important determinant of single-unit baroreceptor activity.

Action Potentials↗

PubMed1988

Activated endothelial cells in culture suppress baroreceptors in the carotid sinus of dog.

Vascular stretch increases the activity of arterial baroreceptors along with the production and release of substances from the endothelium. We hypothesized that endothelial factors modulate the sensitivity of baroreceptors during increases in arterial pressure. Baroreceptor activity was recorded from single fibers innervating the isolated carotid sinus of dogs anesthetized with chloralose after removal of the endothelium (balloon denudation) and after replacing into the denuded sinus bovine aortic endothelial cells cultured on microcarrier beads. The endothelial cells were activated with either the calcium ionophore A23187 (2 microM) or bradykinin (10 microM). The threshold pressure (n = 7) determined with a slow ramp increase in static pressure averaged 73 +/- 7 (SEM) mm Hg during exposure to naked beads and was increased significantly (96 +/- 18 mm Hg; p less than 0.05) during exposure to endothelial cell cultures. During stepwise increases in pressure, activity (n = 6) averaged 14 +/- 5, 40 +/- 8, and 54 +/- 8 spikes/sec at 75, 125, and 175 mm Hg during exposure to naked beads and decreased significantly to 2 +/- 2, 30 +/- 11, and 35 +/- 12 spikes/sec at equivalent pressures during exposure to the cell cultures. The activity was restored after replacement of the cell cultures with naked beads. The suppressed activity was not caused by changes in carotid sinus diameter or strain (sonomicrometers) or by the chemical activators that were also added to the naked beads. The results indicate that chemically activated endothelial cells release an inhibitory factor that suppresses baroreceptor activity.

Animals↗

PubMed1988

New insights into the influence of pulsatile pressure on the arterial baroreceptor reflex.

Pulsatile arterial pressure as compared to static pressure has important influences on baroreceptor activation and on the central mediation of the baroreflex. First, the static pressure-baroreceptor activity curve is sigmoid and the slope or gain peaks abruptly at pressures near 100 mmHg. In contrast, the pulsatile pressure-activity curve is linear over a wide range of pressure and the maximum gain is reduced. Second, exposure of baroreceptors to elevated levels of static pressure causes a rapid resetting or desensitization of the receptors within minutes. Baroreceptor resetting is absent or blunted when the elevated pressure is pulsatile. Third, inhibition of sympathetic activity is greater during pulsatile vs. static pressure even when baroreceptor activity per unit time is less. This central facilitation of the baroreflex is related to the lack of adaptation of central neurons to the pulse phasic afferent activity. The results indicate: 1) the extended linear range of the pressure-activity relation during pulsatile pressure may enable the baroreceptors to accurately detect changes in arterial pressure over a wider pressure range than that predicted from experiments using static pressure; and 2) pulsatile pressure can reduce resetting and promote reflex inhibition of sympathetic activity both by sensitizing the baroreceptors and by centrally facilitating the reflex.

Animals↗

PubMed1987

Prevention or attenuation of baroreceptor resetting by pulsatility during elevated pressure.

Acute static elevation of arterial pressure increases the pressure threshold for activation of baroreceptors (acute resetting). The purpose of this study was to test the hypothesis that pulsatility during acute elevation of pressure modifies this acute resetting. Activity was recorded in 21 single baroreceptor units from the isolated carotid sinuses of dogs anesthetized with chloralose. Single-unit pressure thresholds were determined with a slow ramp increase in pressure. After a control period of static pressure at 25 to 50 mm Hg, the pressure threshold averaged 69 +/- 4 (SE) mm Hg. Three graded levels of static pressure were held for 5 to 15 minutes. The levels averaged 76 +/- 4, 115 +/- 6, and 170 +/- 5 mm Hg. The corresponding nerve activity during these periods was 0, 44 +/- 6, and 63 +/- 6 spikes per second, and the resulting increases in pressure threshold averaged 10 +/- 1, 17 +/- 2, and 26 +/- 3 mm Hg, respectively. In contrast, during equivalent elevations of pulsatile pressure, nerve activity averaged 20 +/- 3, 37 +/- 4, and 61 +/- 5 spikes per second, and the increases in pressure threshold averaged 0 +/- 4, 14 +/- 2, and 24 +/- 2 mm Hg, respectively. In some units, the pressure threshold decreased following elevation of pulsatile pressure. The results indicate that: pulsatility during elevation in pressure prevents or attenuates the acute baroreceptor resetting except at maximal pressure; upward resetting occurs with elevation of static pressure even when there is no nerve activity during the period of elevated pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Contrasting effects of static and pulsatile pressure on carotid baroreceptor activity in dogs.

The purpose of this study was to contrast the effects of static and pulsatile pressure on carotid baroreceptor activity over a wide range of mean arterial pressure. Static and pulsatile pressure were applied to the isolated carotid sinus of dogs anesthetized with chloralose. Recordings were obtained from single baroreceptor units as well as from the whole sinus nerve or a large strand of the nerve. Three observations are reported. First, in single units the pulsatile pressure threshold, which averaged 48 +/- 8 (SEM) mm Hg, was far below the static pressure threshold, which averaged 79 +/- 8 mm Hg (p less than 0.05, n = 15). Thus, pulsatility decreased the threshold by an average of 31 mm Hg in contrast to the minimal or lack of decrease in threshold reported by others in aortic baroreceptors. Second, at moderate arterial pressures a shift from static to pulsatile pressure caused a decrease in single and multiple unit activities. In single units, the decrease approximated 15% (from 42.0 +/- 2.1 to 35.5 +/- 1.9 spikes/sec, p less than 0.05, n = 25). In all units, there was no diastolic nerve activity ("silence") when diastolic pressure was 1 to 10 mm Hg above static pressure threshold; 80% of the units exhibited "diastolic silence" when diastolic pressure was 20-30 mm Hg above threshold and 40% of the units showed silence at diastolic pressures 40-50 mm Hg above threshold. In whole nerve recordings, pulsatility increased activity from 57 +/- 15 to 142 +/- 29 spikes/sec (p less than 0.05) at low mean arterial pressures (50 and 75 mm Hg), as expected from the reduction in pressure threshold noted in single units, and decreased activity by approximately 15% (from 373 +/- 69 to 320 +/- 55 spikes/sec, p less than 0.05, n = 9) at mean arterial pressures of 125 and 150 mm Hg. This decrease in activity with a shift from static to pulsatile pressure at moderate arterial pressures has not been reported previously. Third, the static pressure-activity curve was sigmoid, and its gain peaked sharply at 75-100 mm Hg; in contrast, the pulsatile pressure-activity curve was linear between 25 and 150 mm Hg, and its maximum gain was half the maximum gain during static pressure. These differences between the static pressure-activity curve and the pulsatile pressure-activity curve were noted during both increases and decreases in carotid sinus pressure; both curves exhibited some hysteresis during the decreases in pressure.

Action Potentials↗

PubMed1985

Regional hypoxic pulmonary vasoconstriction in dogs with asymptomatic dirofilariasis.

The pulmonary hemodynamic response to unilateral alveolar hypoxia was investigated in pentobarbital-anesthetized dogs with mild heartworm (HW) disease and in dogs free of HW (HWF). Left lung nitrogen ventilation in HWF dogs resulted in a decrease in the fraction of the cardiac output (QT) perfusing the left lung (QL) from 0.37 +/- 0.03 (SEM) to 0.20 +/- 0.02 (P less than 0.01). In contrast, dogs with mild HW disease did not develop a significant decrease in QL/QT which decreased from 0.38 +/- 0.02 to 0.33 +/- 0.02. This attenuated pulmonary vascular response to regional alveolar hypoxia in dogs with HW disease was associated with a normal pulmonary arterial pressure (14.8 +/- 1.5 mm of Hg) that was not different from that seen in HWF dogs (15.8 +/- 1.7 mm of Hg). These results indicate that mild HW disease interferes with the ability of hypoxic pulmonary vasoconstriction to redistribute pulmonary blood flow away from hypoxic regions of the lung.

Animals↗

PubMedDate not supplied

Rapid adaptation of central pathways explains the suppressed baroreflex with aging.

Aging is associated with suppressed baroreflex function. Renal sympathetic nerve activity was recorded from young (1 year) and old beagles (11 years) during a step rise in isolated carotid sinus pressure. An abrupt increase in pressure resulted in a significant and similar inhibition of efferent nerve activity in both groups, but the inhibition was not sustained in the old as compared with the young animals. The escape from sympathetic inhibition in the old could not be explained by a decline of input from sensory baroreceptor neurons. Thus the defect in the aged animals is caused by a rapid adaptation of central baroreflex neurons to the baroreceptor input instead of a lack of responsiveness of these neurons, suggesting a functional rather than a structural impairment.

Adaptation, Physiological↗

PubMedDate not supplied

Mechanisms of baroreceptor activation.

The determinants of the nerve activity generated at the baroreceptor endings have been examined. 1) In the isolated carotid sinus, the placement of activated bovine aortic endothelial cells decreased baroreceptor activity (BRA) in a reversible manner. Both endothelin and nitric oxide (NO) suppress BRA, whereas prostacyclin (PGI2) increases activity. 2) The BRA in single units declines and often ceases during non-pulsatile increases in carotid sinus pressure sustained over several minutes. This "adaptation" is attenuated by the transient potassium channel (IA) blocker 4-aminopyridine (4-AP) and not by inhibition of the Na+/K+ pump. 3) In preliminary studies, mechano-electrical transduction was examined in isolated and cultured nodose ganglion neurons. Opening of stretch-activated (SA) channels by suction on the cell-attached patch was seen infrequently; however, probing the neurons consistently increased their intracellular calcium [Ca++]i measured with fura-2. This increase in [Ca++]i is blocked by gadolinium (Gd3+), a trivalent lanthanide reported to block SA channels. Gd3+ also blocks the BRA in the carotid sinus. We conclude that paracrine factors significantly modulate BR sensitivity, that selective ionic mechanisms (the 4-AP sensitive K+ channels) determine the degree of "adaptation" of BR to elevated pressure, and that SA channels sensitive to Gd3+ may be the mechano-electrical transducers in BR neurons.

4-Aminopyridine↗