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Biomedical subjects

F M Abboud

Publications and source records attributed to F M Abboud.

At least 19 recordsLinked to original sources
PubMed1992

Parasympathetic hyperresponsiveness and bradyarrhythmias during apnoea in hypertension.

Voluntary end-expiratory apnoea in a 23-year-old asymptomatic mild hypertensive patient consistently elicited bradyarrhythmias (complete heart block and sinus pause) and sympathetic activation to muscle blood vessels, indicating simultaneous sympathetic and parasympathetic activation during apnoea. The sympathetic bradyarrhythmic response to apnoea was potentiated by hypoxia and eliminated by atropine. Baroreflex activation also attenuated the bradycardic response to apnoea. A 43-year-old hypertensive patient with sleep apnoea also exhibited bradyarrhythmias (sinus arrest for up to 10 s) and a fall in perfusion pressure to less than 50 mmHg during episodes of sleep apnoea. These cardiovascular changes were associated with a reduction in oxygen saturation to levels as low as 35%. Neither patient was on any medication. Simultaneous sympathetic and parasympathetic activation during episodes of apnoea may predispose to cardiovascular catastrophe. These chemoreflex mediated autonomic changes are inhibited by baroreflex activation. We propose that patients with impaired baroreflexes (patients with hypertension or heart failure and premature infants) may be especially susceptible to excessive autonomic responses to chemoreflex stimulation during periods of apnoea. In these patient groups, bradyarrhythmias, hypoxia, hypoperfusion and sympathetic activation during apnoea may predispose to sudden death.

Adult↗
PubMed1992

Suppression of baroreceptor discharge by endothelin at high carotid sinus pressure.

Endothelin is a potent vasoconstrictor peptide released from endothelial cells capable of producing marked and prolonged increases in arterial pressure. The purpose of this study was to determine whether endothelin alters the sensitivity of arterial baroreceptors. Multifiber baroreceptor activity was recorded from the vascularly isolated, endothelium-denuded carotid sinus in dogs anesthetized with alpha-chloralose. Local exposure of baroreceptors to endothelin at a concentration of 10(-8) M produced vasoconstriction of the carotid sinus as measured with sonomicrometer crystals but did not alter baroreceptor discharge significantly. A higher concentration of endothelin (10(-7) M) markedly suppressed baroreceptor activity, particularly at pressures greater than 100 mmHg (n = 7, P less than 0.05). The magnitude of the decrease in activity was dependent on the duration of exposure to endothelin. Baroreceptor activity measured at carotid pressures of 60, 100, and 200 mmHg averaged 23 +/- 4, 65 +/- 6, and 100 +/- 0% of maximum during control; 38 +/- 12, 61 +/- 9, and 74 +/- 15% after exposure to endothelin (10(-7) M) for 2 min; and 27 +/- 8, 53 +/- 12, and 56 +/- 19% after 12 min, respectively. The suppression of nerve activity with the high dose of endothelin was not accompanied by additional vasoconstriction, suggesting a direct effect of endothelin on nerve endings. We speculate that endothelin released from endothelial cells may act in a paracrine manner to suppress activity of baroreceptors, particularly at high levels of arterial pressure. Such an action would interfere with the buffering capacity of the baroreflex and promote hypertension.

Animals↗
PubMed1992

Aggregating human platelets in carotid sinus of rabbits decrease sensitivity of baroreceptors.

Aggregating platelets release factors that act in a local paracrine manner to alter vascular tone. The purpose of the present study was to explore the possibility that factors released from aggregating platelets may alter the sensitivity of arterial baroreceptors. Baroreceptor activity was recorded from the vascularly isolated carotid sinus of rabbits anesthetized with sodium pentobarbital. The carotid sinus was filled with oxygenated Krebs-Henseleit buffer and distended with slow ramp increases in nonpulsatile pressure. Sensitivity of baroreceptors to increased pressure was determined before and during intraluminal exposure of the sinus to washed human platelets suspended in Krebs' buffer. Platelets activated with thrombin (0.4 units/ml) decreased baroreceptor activity and the slope of the pressure-activity curve significantly (n = 6). The platelet-induced decrease in baroreceptor sensitivity was related to the duration of exposure to platelets with no change in baroreceptor activity after 4 minutes and a progressive decrease in activity over the next 12 minutes. The slope of the pressure-nerve activity relation averaged 1.26 +/- 0.08 %/mm Hg during control and decreased to 0.97 +/- 0.22, 0.80 +/- 0.19, and 0.53 +/- 0.15 %/mm Hg after 12-16 minutes of exposure to 10(7), 10(8), and 3-6 x 10(8) activated platelets/ml, respectively (p less than 0.05). Baroreceptor sensitivity was restored after removal of platelets from the carotid sinus. Thrombin alone had no effect on baroreceptor sensitivity. Activated platelets did not alter the carotid pressure-diameter relation, suggesting a direct inhibitory effect on baroreceptors. The slope of the pressure-activity curve and maximum baroreceptor activity were not decreased by the stable thromboxane analogue U46619, serotonin, or ADP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Increase in sympathetic activity with age. I. Role of impairment of arterial baroreflexes.

The purpose of this study was to evaluate changes in arterial baroreflex function with aging. Mean arterial pressure (MAP) obtained in the awake state was 110 +/- 7 mmHg in the young animals (1 yr; n = 5) and 128 +/- 6 mmHg in the old beagles (11 yr; n = 11) (P less than 0.05). In response to bolus administration of varying doses of phenylephrine and nitroglycerin in the conscious state, the slope relating heart rate (HR) to MAP was attenuated significantly in the old animals compared with the young (-0.87 +/- 0.30 vs. -2.35 +/- 0.44 beats.min-1.mmHg-1; P less than 0.05). After atropine, the baroreflex control of HR was abolished in both groups. After anesthesia and sectioning of the aortic depressor nerves, and with isolated carotid sinus pressures (CSP) held at 50 mmHg, absolute renal sympathetic nerve activity (RSNA) was significantly greater in the old (368 +/- 40 Hz) vs. the young animals (41 +/- 9 Hz). In the old, the gains of baroreflex inhibition of MAP (0.78 +/- 0.09) and normalized RSNA (0.38 +/- 0.14%/mmHg) during increases in CSP were decreased significantly compared with the young (MAP, 1.16 +/- 0.17 mmHg, and RSNA, 0.72 +/- 0.06%/mmHg). In a subgroup of old normotensive animals (n = 5), the baroreflex gain of RSNA was still attenuated (0.43 +/- 0.11%/mmHg) compared with the young. The reflex reduction in absolute RSNA as a function of baseline RSNA was also impaired in old vs. young beagles.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Increase in sympathetic activity with age. II. Role of impairment of cardiopulmonary baroreflexes.

We have previously shown that arterial baroreflex function is significantly impaired in a group of old beagles [G. Hajduczok, M. W. Chapleau, S. L. Johnson, and F. M. Abboud. Am. J. Physiol. 260 (Heart Circ. Physiol. 29): H1113-H1120, 1991]. In the present study, we determined whether the neural limb of the cardiopulmonary baroreflex control of renal sympathetic nerve activity (RSNA) and the interaction between the arterial and cardiopulmonary reflexes is also impaired with senescence. In the anesthetized state, the aortic nerves were sectioned and carotid sinuses were isolated bilaterally with carotid sinus pressures held at 50 mmHg in both young (1 yr) and old animals (11 yr). In response to graded volume expansion (VE) with 3% dextran (0 to 30 ml/kg iv), the gain of cardiopulmonary baroreflex control of RSNA was significantly lower in the old (5.1 +/- 3%/mmHg) compared with the young (13.4 +/- 3%/mmHg) animals. There were no significant differences in systemic vascular compliance or left ventricular mass index between the two groups. The gain of the carotid sinus baroreflex inhibition of RSNA was significantly attenuated by VE in the young group but was not affected in the old group. Bilateral vagotomy (VX) resulted in a 182 +/- 74% increase in RSNA in the young (P less than 0.05), but VX did not significantly increase RSNA in the old (12 +/- 17%). After VX, the carotid sinus baroreflex gain markedly increased by nearly eightfold in the young group (P less than 0.05) but was not altered in the old dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Rapid baroreceptor resetting in chronic hypertension. Implications for normalization of arterial pressure.

The purpose of this study was to examine the ability of baroreceptors of renal hypertensive rabbits to reset rapidly during acute changes in arterial pressure. The carotid sinus (CS) was vascularly isolated and baroreceptor activity was recorded during slow ramp increases in CS pressure in hypertensive (one-kidney, one wrap; 127 +/- 3 mm Hg) and normotensive (one-kidney, no wrap; 85 +/- 3 mm Hg) rabbits anesthetized with chloralose. Control measurements were made after holding pressure for 10-15 minutes at the level of arterial pressure recorded before each experiment. Baroreceptor threshold pressure (Pth) was higher in hypertensives (78 +/- 4 mm Hg) compared with normotensives (55 +/- 3 mm Hg, p less than 0.05), and nerve activity was less in hypertensives over a wide range of pressure. CS distensibility (sonomicrometers) was not significantly different in the two groups. After increasing holding pressure from control by 30 and 60 mm Hg for 10-15 minutes, the extent of baroreceptor resetting (delta Pth/delta holding pressure x 100%) in normotensives was 39 +/- 6% and 33 +/- 2%, respectively, but only 14 +/- 5% and 9 +/- 3% in hypertensives (p less than 0.05). After decreasing holding pressure by 30 and 60 mm Hg, resetting was similar in normotensives (32 +/- 6% and 28 +/- 3%) and hypertensives (34 +/- 3% and 30 +/- 4%). In hypertensive rabbits, acute (10-15 minutes) exposure of baroreceptors to normotension (71 +/- 4 mm Hg) decreased Pth to 62 +/- 4 mm Hg and increased nerve activity to levels not significantly different from those of normotensive animals without altering CS distensibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Interaction of baroreceptor and chemoreceptor reflex control of sympathetic nerve activity in normal humans.

Animal studies have demonstrated that activation of the baroreflex by increases in arterial pressure inhibits cardiovascular and ventilatory responses to activation of peripheral chemoreceptors (PC) with hypoxia. In this study, we examined the influences of baroreflex activation on the sympathetic response to stimulation of PC and central chemoreceptors in humans. PC were stimulated by hypoxia (10% O2/90% N2) (n = 6) and central chemoreceptors by hypercapnia (7% CO2/93% O2) (n = 6). Responses to a cold pressor stimulus were also obtained as an internal reflex control to determine the selectivity of the interactive influence of baroreflex activation. Baroreflex activation was achieved by raising mean blood pressure by greater than 10 mmHg with intravenous infusion of phenylephrine (PE). Sympathetic nerve activity (SNA) to muscle was recorded from a peroneal nerve (microneurography). During hypoxia alone, SNA increased from 255 +/- 92 to 354 +/- 107 U/min (P less than 0.05). During PE alone, mean blood pressure increased and SNA decreased to 87 +/- 45 U/min (P less than 0.05). With hypoxia during baroreflex activation with PE, SNA did not increase (50 +/- 23 U/min). During hypercapnia alone, SNA increased from 116 +/- 39 to 234 +/- 72 U/min (P less than 0.01). Hypercapnia during baroreflex activation with PE increased SNA from 32 +/- 25 U/min during PE alone to 61 +/- 26 U/min during hypercapnia and PE (P less than 0.05). Like hypercapnia (but unlike hypoxia) the cold pressor test also increased SNA during PE. We conclude that baroreflex activation selectively abolishes the SNA response to hypoxia but not to hypercapnia or the cold pressor test. The inhibitory interaction of the baroreflex and the peripheral chemoreflex may be explained by convergence of baroreceptor and peripheral chemoreceptor afferents on neurons in the medulla.

Adult↗
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

Adrenaline facilitates neurogenic vasoconstriction in borderline hypertensive subjects.

Adrenaline facilitates the neural release of endogenous noradrenaline by stimulating prejunctional beta-receptors on adrenergic nerve endings. Recently, we demonstrated the functional significance of this action in the control of vascular resistance in young subjects with normal blood pressure. In the present study, we tested the hypothesis that the effects of adrenaline on neurogenic vasoconstriction are exaggerated in humans with borderline hypertension. Forearm blood flow was measured simultaneously in the experimental and contralateral arms of seven young men with borderline hypertension. We compared forearm vasoconstrictor responses to a reflex stimulus to noradrenaline release (lower-body negative pressure, LBNP) and to intra-arterial infusion of noradrenaline before and 30 min after brachial artery infusion of adrenaline (50 ng/min). These doses had no systemic effects. In the experimental arm, the vasoconstrictor response to LBNP was 65% greater 30 min after the adrenaline infusion (P = 0.075), whereas the response to intra-arterial noradrenaline decreased by 36% (P greater than 0.1). Forearm vascular responses to LBNP in the contralateral control arm that did not receive adrenaline were similar before and after the adrenaline infusion. The ratio of forearm vasoconstrictor responses (i.e. the increase in forearm vascular resistance) with LBNP to the forearm vasoconstrictor response to noradrenaline in the experimental arm was used as an index of neural release of the neurotransmitter noradrenaline. This ratio increased from 0.8 to 2.1 (P less than 0.05) after the adrenaline infusion. These facilitatory neural after-effects of adrenaline were similar in magnitude to our previous observation in young normotensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Role of vasopressin in cardiovascular and blood pressure regulation.

At low concentrations and in physiologic states vasopressin is a potent antidiuretic hormone. Its cardiovascular effects have been more complex and their role in circulatory adjustments to hypovolemia and hypotension difficult to define with precision. Although recognized as a powerful vasoconstrictor, its pressor effect in intact animals, even at high concentrations, is minimal. The reasons for this blunted pressor response have been explored. This report is a review of previously published work from our laboratories which highlights the direct and indirect vasodilator actions of this hormone in animals and humans. The indirect vasodilator effect is caused by inhibition of sympathetic efferents, and facilitation of the baroreflex through a central action of the hormone and its sensitization of arterial baroreceptors as well as cardiac afferents.

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

Effects of alcohol intake on blood pressure and sympathetic nerve activity in normotensive humans: a preliminary report.

Although several epidemiological studies have shown an association between alcohol consumption and high blood pressure, the mechanisms involved in the pressor effect of alcohol are not clear. We hypothesized that alcohol might increase blood pressure at least in part by increasing sympathetic nerve activity. In a double-blind, placebo-controlled study of seven normotensive subjects (mean age +/- s.e.m. 24.0 +/- 1.5 years), we investigated the effects of oral administration of alcohol (0.75 g/kg body weight, diluted in orange juice) or vehicle on arterial blood pressure, heart rate and muscle sympathetic nerve activity, measured directly in the peroneal nerve by microneurography. Plasma ethanol levels increased from 0 (control) to a range of 47.7 +/- 7.6 to 53.3 +/- 5.0 mg/dl 30 min after alcohol intake. This increase in plasma ethanol was accompanied by a significant increase (P less than 0.05) in mean blood pressure, heart rate and sympathetic nerve activity. The vehicle did not affect any of these parameters. Our data suggest that acute oral administration of a moderate dose of alcohol induces a pressure effect through activation of sympathetic nervous outflow.

Adult↗
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↗