Role of autonomic nervous system on heart rate in experimental hypertension

Heart rate and the role of the autonomic nervous system in hypertensive conscious rats by subtotal nephrectomy were studied. Heart rate is significantly higher in the hypertensive rats. Sympathetic blockade with an intravenous injection of propranolol produces a higher decrease in heart rate of hypertensive rats than in control rats. Intravenous injection of atropine produces an increase in heart rate in both groups of animals. It is significantly higher in the control rats than in hypertensive animals. When the autonomic nervous system is blocked with atropine and propranolol, intrinsic heart rate is similar in both groups of animals. Similar results are obtained after blocking ganglionic transmission with hexamethonium. No significative differences are observed in heart rate after intracerebroventricular injection of hemicholinium-3 between both groups of rats. Results show an increased cardiac sympathetic tone, reduced parasympathetic activities, no alterations in the pacemaker activity and implications of central acetylcholine. These alterations in the autonomic nervous system have an important role in the maintenance of elevated heart rate in this experimental model of arterial hypertension.     

Neuropathy in experimental diabetes: an animal model.

A morphometric study of the common peroneal nerve in early experimental diabetes in rats showed that fibre size was diminished. The reduction in the size of the axon was twice that of the myelin sheath. This may contribute to the understanding of the impaired motor conduction velocity found in diabetics shortly after the onset of their disease.     

Renal denervation: a new treatment option in resistant arterial hypertension

Hypertension is one of the most prevalent cardiovascular risk factors. Despite this high prevalence and a broad availability of effective pharmaceutical agents, a significant proportion of patients do not reach treatment goals. Partly this can be explained by secondary causes of hypertension or non-compliance of patients. Nevertheless, a subgroup of patients can be diagnosed with ‘resistant hypertension’. Activation of the sympathetic nervous system is known to be an important factor in the development and progression of systemic hypertension. In this context, a percutaneous, catheter–based approach has been developed using radiofrequency energy to disrupt renal sympathetic nerves. The first studies have shown this technique to be safe, illustrated by a lack of vascular or renal injury. More importantly, catheter-based renal nerve ablation resulted in a significant reduction in blood pressure on top of traditional medical therapy. Additional to the encouraging effects shown on hypertension, a positive influence of this intervention in other conditions, characterised by sympathetic overactivation, may be expected. Though this technique seems promising, further studies are needed to address long-term safety and efficacy of renal denervation in hypertension and other disease states.     

The placebo effect and the autonomic nervous system: evidence for an intimate relationship

For many subjectively experienced outcomes, such as pain and depression, rather large placebo effects have been reported. However, there is increasing evidence that placebo interventions also affect end-organ functions regulated by the autonomic nervous system (ANS). After discussing three psychological models for autonomic placebo effects, this article provides an anatomical framework of the autonomic system and then critically reviews the relevant placebo studies in the field, thereby focusing on gastrointestinal, cardiovascular and pulmonary functions. The findings indicate that several autonomic organ functions can indeed be altered by verbal suggestions delivered during placebo and nocebo interventions. In addition, three experimental studies provide evidence for organ-specific effects, in agreement with the current knowledge on the central control of the ANS. It is suggested that the placebo effects on autonomic organ functions are best explained by the model of 'implicit affordance', which assumes that placebo effects are dependent on 'lived experience' rather than on the conscious representation of expected outcomes. Nevertheless, more studies will be needed to further elucidate psychological and neurobiological pathways involved in autonomic placebo effects.     

Effect of angiotensin II receptor blockade on autonomic nervous system function in patients with essential hypertension

It has long been proposed that the renin-angiotensin system exerts a stimulatory influence on the sympathetic nervous system, including augmentation of central sympathetic outflow and presynaptic facilitation of norepinephrine release from sympathetic nerves. We tested this proposition in 19 patients with essential hypertension, evaluating whether the angiotensin receptor blockers (ARBs) eprosartan and losartan had identifiable antiadrenergic properties. This was done in a prospective, randomized, three-way placebo-controlled study of crossover design. Patients were randomized to 600 mg of eprosartan daily, 50 mg of losartan daily, or placebo. The treatment period was 4 wk, with 2-wk washout periods. Multiunit firing rates in efferent sympathetic nerves distributed to skeletal muscle vasculature (muscle sympathetic nerve activity, MSNA) were measured with microneurography, testing whether ARBs inhibit central sympathetic outflow. In parallel, isotope dilution methodology was used to measure whole body norepinephrine spillover to plasma. Mean blood pressure on placebo was 151/98 mmHg, with both ARBs causing reductions of approximately 11 mmHg systolic and 6 mmHg diastolic pressure, placebo corrected. Both MSNA [35 +/- 12 bursts/min (mean +/- SD) on placebo] and whole body norepinephrine spillover [366 +/- 247 ng/min] were unchanged by ARB administration, indicating that the ARBs did not materially inhibit central sympathetic outflow or act presynaptically to reduce norepinephrine release at existing rates of nerve firing. These findings contrast with the easily demonstrable reduction in sympathetic nervous activity produced by antihypertensive drugs of the imidazoline-binding class, which are known to act within the brain to inhibit sympathetic nervous outflow. We conclude that sympathetic nervous inhibition is not a major component of the blood pressure-lowering action of ARBs in essential hypertension.     

Effect of juvenile hormone on the autonomic nervous system

The effects of juvenoids on the autonomic nervous system, which controls certain physiological functions by means of special extracardiac pulsations in hemolymph pressure, have been studied in pupae of the mealworm, Tenebrio molitor. Prolonged tensiometric monitoring of the hemolymph pressure changes revealed that the extra-pupal development that had been caused by juvenoids evoked unusual reappearance of prepupal pattern of extracardiac pulsations. By contrast, the specific pharate adult types of the pulsations completely disappeared. The functioning of the autonomic nervous system was aberrant or incomplete during an unsuccessful extra-pupal ecdysis. It is suggested that malfunction of the autonomic nervous system in the extra-pupal instars may be the reason for the ecdysial failures associated with the use of juvenoids.     

Basal ganglia and functions of the autonomic nervous system

1. The aim of this mini-review was to describe an underrecognized but important aspect of the basal ganglia diseases, the dysfunction of the autonomic nervous system that patients suffer owing to the degenerative process affecting these structures, mainly Parkinson's disease.2. We analyze the most prevalent autonomic abnormalities in these patients from an experimental and clinical point of view.     

The occurrence of analgesia in an animal model of hypertension

The relationship between blood pressure and pain sensitivity in a spontaneously hypertensive strain of rats (SH) was studied. Both analgesia and systolic blood pressure (SBP) were determined in SH and Wistar-Kyoto (WK) rats between 30 and 70 days of age. The SBP of the 30 day old SH rat was not significantly different from that of the WK rat (SH = 102±10 mmHg; WK = 93±12 mm Hg). Howeverm, the yooung SH rat exhibited considerably more analgesia than corresponding, age matched, WK rats. The SH rat jump latency was 45±10 seconds whereas the WK rat latency was 21±6 seconds. Both naloxone and atropine attenuated the analgesia of the SH rat but did not significantly alter the response of the WK rat. Methyl-alropine did not affect either the SH or WK rat response. These data suggest the presence of higher endorphin-like activity in the SH rat and a possible relationship between endogenous opioid pathways and the development of hypertension.     

New transmitters and new targets in the autonomic nervous system

Several recent findings have made research into the autonomic nervous system even more. exciting, such as the revelation that nitric oxide is a major neurotransmitter, the delineation of the physiological roles for purines and vasoactive intestinal peptide, and the discovery that the interstitial cells of Cajal are major target cells for enteric innervation. Nitric oxide is probably the major neurotransmitter evoking inhibitory junction potentials in smooth muscle. ATP is a mediator of non-adrenergic non-cholinergic enteric innervation, as well as being a fast neurotransmitter in peripheral and autonomic neuro-neuronal synapses. The interactions between enteric nerves and both immune cells and interstitial cells of Cajal (as pacemaker cells of gut smooth muscle) are forcing a rethink of many aspects of gut physiology.