Modulation of baroreceptor activity by ionic and paracrine mechanisms: an overview

1. The primary mechanism of activation of baroreceptors is mechanical deformation during vascular stretch. In addition, baroreceptor activity is modulated by ionic mechanisms and by neurohumoral and paracrine factors that act directly on the nerve endings. 2. Ionic mechanisms play a major role in causing baroreceptor activity to decline during a sustained increase in arterial pressure (adaptation) and in the suppression of activity that occurs after pressure returns to basal levels (post-excitatory depression). Activation of a 4-aminopyridine-sensitive K+ channel contributes to adaptation, whereas activation of an electrogenic sodium pump is responsible for post-excitatory depression. 3. Factors released from vascular endothelium exert powerful effects on baroreceptor sensitivity. Prostacyclin increases baroreceptor sensitivity and contributes to baroreceptor activation during vascular stretch. Nitric oxide, endothelin and oxygen-derived free radicals suppress baroreceptor activity particularly at high levels of arterial pressure. The sympathetic neurotransmitter norepinephrine modulates baroreceptor activity: a) indirectly through its vasoconstrictor action, b) directly by binding to alpha-adrenergic receptors on the nerve endings, and c)through release of a cyclooxygenase metabolite, possibly prostacyclin, from endothelium. 4. Endothelial dysfunction contributes to baroreceptor impairment in atherosclerosis and in chronic hypertension. Loss of the excitatory influence of prostacyclin and increased formation of free radicals and possibly endothelin contribute to the baroreceptor dysfunction. Platelets aggregating at sites of endothelial damage in the carotid sinus release a stable diffusible factor that impairs baroreceptor sensitivity. 5. Therapeutic interventions may alter baroreceptor sensitivity through paracrine mechanisms. Treatment of hypertension or atherosclerosis may improve baroreceptor sensitivity by restoring endothelial function. Antiplatelet agents may enhance baroreceptor sensitivity. Antidepressant agents may decrease baroreceptor sensitivity by inhibiting prostacyclin and/or stimulating nitric oxide formation, which may contribute to dysregulation of the circulation in patients treated for depression.

Role of vagal and sinoaortic baroreflexes in circulatory adjustments to passive head up tilt.

To evaluate the contribution of vagal and sinoaortic baroreflexes in circulatory adjustments anaesthetized rabbits were subjected to 70 degree head up tilt with (i) both reflexes intact; (ii) after elimination of sinoaortic reflexes; (iii) after elimination of vagal reflexes; and (iv) after elimination of both categories of reflexes. The results suggest that vagal mediated baroreflexes from cardiopulmonary baroreceptors contribute significantly in circulatory adjustments to passive head up tilt while sinoaortic baroreflexes play the major role.

Carotid body chemoreceptor excitation produced by carotid occlusión

En 20 gatos adultos anestesiados con pentobarbitona, se registró la actividad eléctrica aferente del nervio carotídeo (sinusal). La oclusión de la arteria carótida común ipsilateral disminuyó la presión intrasinusal a 15-100 torr (dependiendo de la presión previa) y silenció la descarga barosensorial. En gatos que respiraban aire y con presión arterial media bajo 125 torr, la oclusión ipsilateral produjo aumento de la frecuencia de descarga quimiosensorial, de aparición rápida (latencia = 4 s), que alcanzó el máximo a los 30 s y después se mantuvo a un nivel submáximo de descarga (80-90% de la frecuencia máxima) al menos por 10 minutos. La oclusión carotídea ipsilateral practicada a estos mismos gatos mientras respiraban 100% O2 produjo excitación quimiosensorial de comienzo más tardío (latencia = 20 s) y menor magnitud (30-40% de la frecuencia máxima en normoxia). La oclusión carotídea ipsilateral practicada cuando la presión arterial media estaba sobre 130 torr sólo aumentó transitoriamente la frecuencia quimiosensorial o suprimió su fluctuación ventilatoria. La oclusión carotídea bilateral redujo pronunciadamente la presión intrasinusal y aumentó considerablemente la frecuencia quimiosensorial. La aplicación de estímulos químicos (inhalación de 100% N2 por 5-10 s, inyección i.v. de NaCN) durante las oclusiones carotídeas aumentó más aún la frecuencia de descarga quimiosensorial, indicando que el flujo sanguíneo a través del cuerpo carotídeo no estaba detenido. Se concluye que la oclusión carotídea puede provocar excitación quimiosensorial, cuya magnitud depende de la duración de la maniobra y condiciones circulatorias y ventilatorias prevalentes. Se sugiere que la excitación quimiosensorial podría interactuar con la desactivación barosensorial en la generación de los cambios reflejos evocados por oclusión carotídea

Diuresis during fluid infusion : buffer nerve and spinal influences on it.

The rate and cumulative volume of diuresis were measured sequentially for each incremental infusion dose of 5 ml/kg body weight till a 100 ml/kg or more dose was reached. Normal saline (NS), Ringer-Locke (RL) and tender coconut water (TCW) were infused in three groups each of paraldehyde (PLD), and chloralose and urethane (C & U) anaesthetised dogs. The slow infusion rate of about 0.5 ml/kg/min was used. The RL infusion was repeated in vagotomised and/or carotid sinus (CS) denervated dogs and spinal dogs with or without intact vagi. During the NS and RL infusion schedules in PLD anaesthetised dogs produced much less urine than C & U groups. The order of minimum to maximum diuretic effect caused by these fluids were RL, NA and TCW in PLD groups and NA, TCW and RL in C & U groups. The study indicates that the type of anaesthesia and the composition of infusion fluid determines the rate of infusion induced diuresis. PLD anaesthesia has antidiuretic effect, which is not overcome by vagotomy. In C & U anaesthetised dogs the vagotomy and CS denervation performed separately greatly increased the rate of infusion induced diuresis but the diuresis largely decreased when combined surgery was performed. The diuresis in spinal dogs was very low, though in the vagotomised-spinal dogs, the rate of diuresis was more than in the spinal dogs.