Alterations in plasma neuropeptide Y immunoreactivity and catecholamine levels during surgical removal of pheochromocytoma.

BACKGROUND: Neuropeptide Y, an abundant neurohormone present with catecholamines in the adrenal medulla, is a potent non-adrenergic vasoconstrictor and a vascular growth factor. OBJECTIVE: To determine the mechanism of the release from, and possible role of neuropeptide Y in, pheochromocytomas, compared with those of catecholamines. METHODS: Plasma and tumour levels of neuropeptide Y-immunoreactivity (by, radioimmunoassay) and of noradrenaline and adrenaline (by a radioenzymatic method) in 29 patients (19 women and 10 men, aged 22-68 years) were measured during surgical removal of the tumour, during alpha-adrenergic and beta-adrenergic blockade. Arterial systemic blood samples were withdrawn before the ligation of the vessels supplying the tumour, during its surgical manipulations and after its removal, while haemodynamics was monitored. RESULTS: Plasma neuropeptide Y levels in 17 patients (58.6%, group I) significantly increased during manipulations of the pheochromocytoma and returned completely to normal after its removal. This response was independent of the plasma neuropeptide Y immunoreactivity manipulation and was correlated to increases in plasma noradrenaline (r = 0.638, P < 0.02) but not adrenaline levels. Manipulation-induced increases in plasma neuropeptide Y-immunoreactivity were associated with greater neuropeptide Y content in tumours (r = 0.508, P < 0.05) but neither plasma nor tumour levels of neuropeptide Y immunoreactivity were correlated to tumour mass. Plasma levels of neuropeptide Y immunoreactivity in the remaining 12 patients (41.4%, group II) remained unchanged throughout the experimental period, while levels of circulating catecholamine rose. In all, in spite of our attempt at complete adrenergic blockade, tumour manipulation elevated arterial blood pressure and these changes were significantly correlated to increases in levels of catecholamines in patients in both groups but also to plasma neuropeptide Y immunoreactivity in patients in group I. CONCLUSION: Pheochromocytomas exhibit different patterns of secretion. For about half of the patients either the secretion of neuropeptide Y is uncoupled from that of catecholamines or its secretion could be obscured by an increase in degradation of neuropeptide Y to inactive fragments undetectable by radioimmunoassay.

Carotid baroreceptor reflex in man, its modulation over the respiratory cycle.

Carotid baroreceptors were stimulated in 40 healthy volunteers by a rapid increase of the carotid transmural pressure due to subatmospheric pressure applied to a tight neck chamber (neck suction). Heart rate, arterial blood pressure and respiratory response were recorded. Reflex vagal inhibition of the sinus node preceded a blood pressure fall. Cardiac response adapted in a few seconds during prolonged baroreceptor stimulation, whereas reflex hypotension was maintained over the whole stimulation period applied up to 30 s. Augmented inspiratory movements were observed during neck suction. Short-lasting baroreceptor stimuli produced much less cardiac inhibition if applied during the early inspiratory than during the expiratory phase. On the peak and on the plateau of the voluntarily sustained deep inspirations, a spontaneous sinus bradycardia and a facilitation of the baroreceptor-cardiac reflex appeared. Voluntarily delayed expiration following deep and sustained inspiration coincided with cardioacceleration and baroreflex inbibition. Thus voluntarily Imposed, breathing patterns may reverse both respiratory sinus arrhythmia and cyclical modulation of the baroreflex responsiveness over the respiratory cycle.

Muscarinic cholinergic receptors modulate vagal cardiac responses in man.

Respiratory sinus arrhythmia (peak-valley P-P interval changes during controlled breathing) and carotid baroreceptor-cardiac reflex responses (provoked by neck suction) were studied before and after low (0.725 microgram/kg) or high (0.043 mg/kg) dose atropine sulfate infusions in 22 healthy young adults. There was a highly significant (r = 0.78, P = 0.002) correlation between resting respiratory sinus arrhythmia and baroreflex responses. Low dose atropine increased the magnitude of sinus arrhythmia and baroreflex responses. Large dose atropine reduced sinus arrhythmia and baroreflex responses in an exponential fashion. Our results link respiratory sinus arrhythmia with baroreflex responsiveness and provide inferential evidence that vagal cardiac efferent activity is modulated by inhibitory cholinergic receptors. We speculate that blockade of these receptors by low doses of atropine amplifies vagal motoneuron responses to incoming baroreceptor information, and thereby increases average maximum and minimum levels of vagal cardiac outflow during breathing.

Trigeminal-baroreceptor reflex interactions modulate human cardiac vagal efferent activity.

Instantaneous levels of vagal cardiac inhibition reflect integrated responses of vagal motonuclei to multiple sensory neural inputs. We studied how two of these inputs, from trigeminal cutaneous receptors and carotid arterial baroreceptors interact to influence human vagal cardiac outflow. Nine healthy young men voluntarily maintained breathing rates and tidal volumes within narrow limits. Carotid baroreceptors were stimulated with brief periods of moderate neck suction. Volunteers were studied prone, breathing through a snorkel, before and during face immersion in cold water, and before and after an intravenous injection of a very low dose of atropine sulphate (which increases vagal cardiac efferent activity in dogs). Face immersion raised blood pressure slightly, increased heart period, and augmented baroreflex bradycardia and respiratory sinus arrhythmia significantly. Low-dose atropine together with face immersion further augmented blood pressure, heart period, baroreflex responses and sinus arrhythmia. These results suggest that one input to the central nervous system (from trigeminal cutaneous receptors) which increases vagal cardiac outflow, augments vagal responses to another input (from arterial baroreceptors). Since the initial pathways of these two inputs are anatomically separate, it is likely that the influences of respiration and low doses of atropine on vagal motonuclei are exerted down-stream from the termination of primary trigeminal and baroreceptor afferent fibres.

Surface and shape of the optic disc in healthy subjects in various age groups. Application of computer picture processing.

The method of computer analysis with the Digital Image Transformer system for assessment of the shape of optic disc and optic cup and disc/cup ratio in healthy subjects is described. The relationship of these parameters of age was also studied.