Effect of carotid and aortic baroreceptors on cardiopulmonary reflex: the role of autonomic function

We determined the sympathetic and parasympathetic control of heart rate (HR) and the sensitivity of the cardiopulmonary receptors after selective carotid and aortic denervation. We also investigated the participation of the autonomic nervous system in the Bezold-Jarish reflex after selective removal of aortic and carotid baroreceptors. Male Wistar rats (220-270 g) were divided into three groups: control (CG, N = 8), aortic denervation (AG, N = 5) and carotid denervation (CAG, N = 9). AG animals presented increased arterial pressure (12 percent) and HR (11 percent) compared with CG, while CAG animals presented a reduction in arterial pressure (16 percent) and unchanged HR compared with CG. The sequential blockade of autonomic effects by atropine and propranolol indicated a reduction in vagal function in CAG (a 50 and 62 percent reduction in vagal effect and tonus, respectively) while AG showed an increase of more than 100 percent in sympathetic control of HR. The Bezold-Jarish reflex was evaluated using serotonin, which induced increased bradycardia and hypotension in AG and CAG, suggesting that the sensitivity of the cardiopulmonary reflex is augmented after selective denervation. Atropine administration abolished the bradycardic responses induced by serotonin in all groups; however, the hypotensive response was still increased in AG. Although the responses after atropine were lower than the responses before the drug, indicating a reduction in vagal outflow after selective denervation, our data suggest that both denervation procedures are associated with an increase in sympathetic modulation of the vessels, indicating that the sensitivity of the cardiopulmonary receptors was modulated by baroreceptor fibers.

Renin angiotensin system and cardiac hypertrophy after sinoaortic denervation in rats

OBJECTIVE: The aim of this study was to evaluate the role of angiotensin I, II and 1-7 on left ventricular hypertrophy of Wistar and spontaneously hypertensive rats submitted to sinoaortic denervation. METHODS: Ten weeks after sinoaortic denervation, hemodynamic and morphofunctional parameters were analyzed, and the left ventricle was dissected for biochemical analyses. RESULTS: Hypertensive groups (controls and denervated) showed an increase on mean blood pressure compared with normotensive ones (controls and denervated). Blood pressure variability was higher in denervated groups than in their respective controls. Left ventricular mass and collagen content were increased in the normotensive denervated and in both spontaneously hypertensive groups compared with Wistar controls. Both hypertensive groups presented a higher concentration of angiotensin II than Wistar controls, whereas angiotensin 1-7 concentration was decreased in the hypertensive denervated group in relation to the Wistar groups. There was no difference in angiotensin I concentration among groups. CONCLUSION: Our results suggest that not only blood pressure variability and reduced baroreflex sensitivity but also elevated levels of angiotensin II and a reduced concentration of angiotensin 1-7 may contribute to the development of left ventricular hypertrophy. These data indicate that baroreflex dysfunction associated with changes in the renin angiotensin system may be predictive factors of left ventricular hypertrophy and cardiac failure.

Acute and chronic electrical activation of baroreceptor afferents in awake and anesthetized subjects

Electrical stimulation of baroreceptor afferents was used in the 1960's in several species, including human beings, for the treatment of refractory hypertension. This approach bypasses the site of baroreceptor mechanosensory transduction. Chronic electrical stimulation of arterial baroreceptors, particularly of the carotid sinus nerve (Hering's nerve), was proposed as an ultimate effort to treat refractory hypertension and angina pectoris due to the limited nature of pharmacological therapy available at that time. Nevertheless, this approach was abandoned in the early 1970's due to technical limitations of implantable devices and to the development of better-tolerated antihypertensive medications. More recently, our laboratory developed the technique of electrical stimulation of the aortic depressor nerve in conscious rats, enabling access to hemodynamic responses without the undesirable effect of anesthesia. In addition, electrical stimulation of the aortic depressor nerve allows assessment of the hemodynamic responses and the sympathovagal balance of the heart in hypertensive rats, which exhibit a well-known decrease in baroreflex sensitivity, usually attributed to baroreceptor ending dysfunction. Recently, there has been renewed interest in using electrical stimulation of the carotid sinus, but not the carotid sinus nerve, to lower blood pressure in conscious hypertensive dogs as well as in hypertensive patients. Notably, previous undesirable technical outcomes associated with electrical stimulation of the carotid sinus nerve observed in the 1960's and 1970's have been overcome. Furthermore, promising data have been recently reported from clinical trials that evaluated the efficacy of carotid sinus stimulation in hypertensive patients with drug resistant hypertension.

Time structure, temporal correlation and coherence of chemosensory impulses propagated through both carotid nerves in cats

In spontaneously breathing, pentobarbitone anesthetized cats, we recorded simultaneously the impulses in the chemosensory fibers of both carotid (sinus) nerves, to analyze the correlations between the frequencies of chemosensory discharges (f chi) and their activation ({df chi/dt}a) and deactivation ({df chi/dt}d) rates. We studied the chemosensory responses to brief exposures to hypoxia (100 percent N2; 5-s and 10-s) and hyperoxia (100 percent O2; 30-s), and intravenous injections of excitatory (NaCN 0.2-100 micrograms/kg) and inhibitory (dopamine hydrochloride 0.02-20 micrograms/kg) chemoreceptor agents. Hypoxia increased f chi, with a high temporal correlation between frequency levels in both nerves. Prolonging hypoxic stimulation increased {df chi/dt}d, with preservation of {df chi/dt}a. Hyperoxic exposure produced highly correlated decreases in f chi in both nerves, but reduced correlation in df chi/dt. Increasing doses of NaCN produced analogous increments in f chi, df chi/dt and their correlations, the {df chi/dt}a/{df chi/dt}d ratio remaining constant along all the experimental range, except in one animal in which the ratio increased in both nerves alike. Dopamine reduced f chi bilaterally, with chemosensory silencing being reached with doses of about 0.2-0.5 microgram/kg, the correlations between f chi's of both nerves remaining constant within the range analyzed. Maximal {df chi/dt}d was not affected along the range of dopamine doses, except in one animal in which it increased in both nerves. It is concluded that both carotid nerves convey similar quantitative information to the brain stem. Thus, the carotid nerves constitute either cooperative inputs or redundant afferences contributing to a high safety factor

Tratamiento del síncope mediante denervación del seno carotídeo / Treatment of syncope by means of carotid sinus denervation

Con el objetivo de resolver simultáneamente los aspectos cardioinhibidor y vasodepresor del síndrome de seno carotídeo, se ha realizado denervación de la bifurcación de la arteria carótida de enfermos que respondieron con pausa R-R mayor a tres segundos en el electrocardiograma o disminución de más de 10 mmHg en la tensión arterial. Los resultados se compararon con los de un grupo de enfermos tratados mediante implante de marcapaso cardiaco definitivo. Se incluyen 17 pacientes, sexo masculino, edad promedio 76.8 años, hipotensión arterial de 25 mmHg y pausa de 4.4 segundos en respuesta al estímulo carotídeo. Siete pacientes del grupo estudiado (85 por ciento) y diez del grupo control (70 por ciento) quedaron asintomáticos y con respuesta normal al estímulo carotídeo, lo que confirma la utilidad del procedimiento