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

Abstract

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. Using an electroneurographic approach, the authors demonstrated that in chronic renin-induced hypertensive dogs there were fewer impulses along the carotid sinus nerve than in the normotensive situation. The investigators hypothesized that there is an adaptation within the baroreceptor end organ, which perpetuates, rather than protects against, an elevation in blood pressure. However, in 1958, Warner (2) demonstrated that activation of the baroreflex by direct electrical stimulation of the carotid sinus nerve (Hering's nerve) reduced arterial pressure in anesthetized normotensive dogs for periods lasting up to 90 min. Subsequent work showed that electrical stimulation of the carotid sinus nerve for 10 to 20 s in patients undergoing head and neck surgery elicited similar results,

Baroreflex activation in conscious rats modulates the joint inflammatory response via sympathetic function

“…Taking into account that anesthesia attenuates baroreflex function (Palmisano et al, 1991;Tanaka and Nishikawa, 1999;Akine et al, 2001;Bassani et al, 2013), our laboratory developed a technique to electrically activate the aortic depressor nerve, an afference of the baroreflex, in conscious rats. We demonstrated that electrical stimulation of the aortic depressor nerve activates the baroreflex promoting bradycardia and hypotension, under physiological (De Paula et al, 1999;Durand et al, 2009) and pathophysiological conditions (Salgado et al, 2007;Durand et al, 2009Durand et al, , 2012, without the undesirable effects of anesthesia. Moreover, electrical stimulation of the aortic depressor nerve in conscious rats shifts the sympathovagal balance toward a parasympathetic predominance (Krieger et al, 1982;Chapleau et al, 1988).…”

Autonomic Regulation of Inflammation in Conscious Animals

“…Anesthetized animals are influenced by the direct effects of general anesthesia and are submitted to eliminating higher central nervous system control of the neural reflex pathways involving the cardiovascular system [34][35][36]. Accordingly, anesthesia attenuates the arterial baroreflex [37][38][39][40][41][42][43]. Moreover, anesthetics can induce relevant anti-inflammatory effects not mimicking the real innate immune responses observed in conscious animals [44,45], and studies involving the neuromodulation of the immune system have been usually performed in anesthetized animals.…”

Evidence that blood pressure remains under the control of arterial baroreceptors in renal hypertensive rats

“…Recent studies on conscious spontaneously hypertensive rats (10,11) demonstrated that when electrical stimulation of the aortic depressor nerve bypassed the impaired sensitivity of the baroreceptors on the arterial wall, the inhibition of the sympathetic system by the baroreceptors was well preserved. We have shown that in chronic renal hypertensive rats (12) the baroreceptors reset to hypertensive levels and still maintain the inhibitory activity on the splanchnic nerve in an apparently normal fashion.…”