Carotid sinus reflexes during postural changes, naturally elicited fighting behaviour, and phases of sleep in the cat.

Reflex responses of mean blood pressure and of heart rate to either bilateral common carotid occlusion (CO) or unilateral carotid sinus dilatation (CSD) during rest and different behaviours have been compared in conscious cats. Unloading and loading the carotid sinus receptors elicited equal reflex responses both of mean blood pressure and of heart rate during control immobile behaviour (CO: +34 +/- 6 mmHg and +35 +/- 6 beats . min-1; CSD: -37 +/- 4 mmHg and -52 +/- 11 beats . min-1), standing on the hindlimbs (CO: +36 +/- 5 mmHg and +29 +/- 5 5 beats . min-1; CSD: -40 +/- 6 mmHg and -61 +/- 10 beats . min-1), fighting against an attacking animal (CO: +34 +/- 5 mmHg and +31 +/- 5 beats . min-1; CSD: -37 +/- 5 mmHg and -56 +/- 10 beats . min-1), quiet wakefulness (CO: +37 +/- 5 mmHg and +38 +/- 4 beats . min-1; CSD: -34 +/- 4 mmHg and -53 +/- 8 beats . min-1) and synchronised sleep (CO: +36 +/- 5 mmHg and +37 +/- 4 beats . min-1; CSD: -36 +/- 4 mmHg and -52 +/- 6 beats . min-1). Desynchronised sleep was associated with an identical response to CSD (-30 +/- 4 mmHg and -51 +/- 7 beats . min-1) but with a reduced (p less than 0.01) reflex response to CO (+18 +/- 3 mmHg These data indicate that carotid sinus baroreflexes largely maintain their ability to modulate pressure upwards and downwards when blood pressure has been reset at somewhat higher levels by standing and fighting and at somewhat lower levels by synchronised sleep. The selective depression of carotid occlusion responses during desynchronised sleep suggests a central or peripheral shift of the baroreflex stimulus-response curve or a selective central inhibition of the reflex response to baroreceptor unloading.

Reflex vasopressin and renin modulation by cardiac receptors in humans.

Animal studies have shown that vasopressin secretion is modulated by arterial baroreceptors and cardiopulmonary volume receptors. Whether this is the case also in humans is controversial, however. To determine whether vasopressin is reflexly modulated by cardiac volume receptors, we studied the effect on plasma vasopressin (venous blood, radioimmunoassay) of reducing venous return and left ventricular end-diastolic diameter (echocardiography) by producing a 20-minute lower body negative pressure in 14 healthy subjects (aged 49.3 +/- 3.8 years, mean +/- SEM). The data were compared with those of 14 age-matched heart-transplant recipients, i.e., subjects with cardiac denervation. In healthy subjects, lower body negative pressure at -15 mm Hg caused a modest reduction in left ventricular end-diastolic diameter (-5 +/- 3.4%) and no change in vasopressin, whereas lower body negative pressure at -37.5 mm Hg caused a more marked reduction in left ventricular end-diastolic diameter (-12 +/- 2.5%) and a small, variable, but overall statistically significant (p < 0.05) increase in vasopressin (+145 +/- 46%, p < 0.01). The left ventricular end-diastolic diameter changes induced by the two lower body negative pressure stimuli were similar in heart-transplant recipients, but the vasopressin increase seen with the lower body negative pressure at -37.5 mm Hg was abolished. The marked increase in plasma renin activity and forearm vascular resistance induced by lower body negative pressure in healthy subjects was also abolished or drastically attenuated in heart-transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental meningeal carcinomatosis selectively depresses local cerebral glucose utilization in rat brain.

Using quantitative autoradiography, we investigated the effect of meningeal carcinomatosis on local cerebral glucose utilization (LCGU). A rat model of meningeal carcinomatosis using Walker 256 tumor was used. LCGU was evaluated using 14C-2-deoxy-D-glucose according to the Sokoloff method. Thirty-one neuroanatomic structures were evaluated, both separately and as part of five functional or neuroanatomic groups: olfactory, auditory, visual, limbic, and white matter. The relationship between tumor and LCGU of underlying brain was examined. Compared with controls, there was no global change of LCGU in the experimental group that applied to all structures. However, mean LCGU was significantly depressed in olfactory cortex, temporal cortex, olfactory tubercle, amygdala, caudate/putaman, inferior colliculus, medial geniculate, anterior commissure, and corpus callosum, and the functional groups that make up the olfactory and auditory systems. There was no correlation between extent of regional tumor burden and degree of depression of LCGU in underlying structures. In meningeal carcinomatosis, tumor results in selective regional depression of LCGU. This occurs both in structures underlying tumor and those anatomically remote, but in certain cases, functionally related to structures subadjacent to tumor. These data may help to explain the diversity of neurologic dysfunction seen in patients with meningeal cancer.

Effects of antihypertensive treatment on vasopressin secretion and on its osmoregulation in moderate hypertension.

BACKGROUND: Changes in plasma osmolality and arterial pressure can affect the secretion of vasopressin (AVP). OBJECTIVE: To investigate the effect of a drug-induced lowering of the arterial pressure on the plasma concentration of AVP and on its osmoregulation in moderately severe uncomplicated hypertensives. DESIGN AND METHODS: A group of 33 moderate uncomplicated and untreated essential hypertensives of both sexes (mean age 48 +/- 1 years, average arterial pressure 171 +/- 3/108 +/- 2 mmHg) was studied. We measured AVP and other plasma and urine variables in 21 of them before and after administration of a hypertonic NaCl solution (100 mmol NaCl in 50 ml). Antihypertensive treatment with a single drug or, if necessary, with a combination of drugs was initiated for eight of these subjects and hypertonic saline administration was repeated after 1 month of treatment. The hypertonic stimulus was administered to the other 12 subjects after acute lowering of the arterial pressure by continuous intravenous infusion either of 0.3 mg clonidine in 100 ml (n = 6) or of 50 mg sodium nitroprusside in 250 ml (n = 6). RESULTS: Administration of hypertonic saline to untreated hypertensives increased their AVP level from 1.6 +/- 0.28 to 5.4 +/- 0.7 pg/ml (n = 21, P < 0.01). Their mean arterial pressure was lowered after pharmacological treatment for 1 month (n = 8) from 125 +/- 2 to 101 +/- 2 mmHg; their baseline AVP level remained unchanged (1.2 +/- 0.21 versus 0.9 +/- 0.25 pg/ml); after hypertonic saline had been administered to hypertensives with lowered arterial pressures, their AVP level increased to 6.0 +/- 1.03 pg/ml (P < 0.01). The AVP level in subjects whose MAP had been lowered acutely by administration of clonidine (n = 6) or of sodium nitroprusside (n = 6; on the average, from 132 +/- 3 to 110 +/- 4 mmHg) increased concurrently from 1.6 +/- 0.63 to 3.4 +/- 0.7 pg/ml (P < 0.05); after administration of the hypertonic saline the AVP level increased to 10.8 +/- 2.22 pg/ml (P < 0.01). This stimulated value was significantly (P < 0.01) higher than that observed after hypertonic saline had been administered to untreated hypertensives (5.4 +/- 0.7 pg/ml). CONCLUSIONS: Acute lowering of the arterial pressure in moderate essential hypertension appears to facilitate the secretion and osmoregulation of AVP. On the other hand, during prolonged antihypertensive treatment, baroreflex regulation of the secretion of AVP appears to be set at a lower operating point, thus exerting the same influence on the release of AVP as it did before antihypertensive treatment.

Potential disynaptic pathways connecting the fastigial pressor area and the paraventricular nucleus of the hypothalamus in the rat.

Efferents from the cardiovascular portion of the fastigial nucleus (rFN), whose electrical stimulation has been found to elicit secretion of vasopressin in the rat, have been traced by use of the anterograde fluorescent tracer Fast blue (FB). In the same animal the retrograde marker Diamidino yellow (DY) was injected in the paraventricular nucleus of the hypothalamus (PVH) to trace afferents to the neurosecretory cells of the hypothalamus. Frontal sections of the brainstem have been analyzed and the FB-labeled axons and terminals and the DY-labeled cells mapped. Both efferents from the rFN and cells projecting to the PVH were found in close contact in the region of the locus coeruleus and parabrachial nucleus (lateral division) and in the caudal ventrolateral medulla, dorsal to the lateral reticular nucleus. Those two regions may function as putative relay stations of disynaptic pathways linking the rFN to the PVH.

Arterial pressure and heart rate changes during natural sleep in rat.

Mean arterial pressure and heart rate data during quiet wakefulness and phases of sleep in conscious rat are sampled by a computer at a rate of 100/sec. Average values and variability expressed as standard deviation are computed for each recording session. Mean arterial pressure and heart rate and their variability decrease from quiet wakefulness to synchronized sleep. During desynchronized sleep, mean arterial pressure increases to the level of quiet wakefulness, and is more variable than during synchronized sleep. Heart rate is lower and more uniform during sleep than during quiet wakefulness, and there is no difference between synchronized and desynchronized sleep except that a greater variability occurs during desynchronized sleep. The study shows that characteristic and specific cardiovascular changes accompany the phases of sleep and that a hierarchy of arterial pressure is present during the resting behavior in rat.

Osmoregulation of vasopressin during acute lowering of arterial pressure by clonidine in moderate hypertension.

Hypertonic saline (100 mmol in 50 ml) was injected intravenously over 5 min in two groups of moderate essential hypertensive patients (group 1, n = 13; group 2, n = 6). In group 2, arterial pressure had been lowered by infusion of clonidine (0.3 mg in 100 ml saline), from 186 +/- 8/116 +/- 3 to 146 +/- 9/98 +/- 5 mmHg (mean +/- s.e.m.). The hypertonic stimulus increased the plasma osmolality of all subjects from 288 +/- 1 to 296 +/- 1 mosmol/kg (P less than 0.01). Plasma vasopressin increased from baseline values that were not significantly different (P less than 0.01) in each of the two groups. The increase in plasma vasopressin was significantly greater (P less than 0.05) in the group 2 hypertensives with a reduced arterial pressure (+7.81 +/- 1.79 pg/ml) than in the group 1 untreated hypertensives (+3.15 +/- 1.2 pg/ml). In our study, acute lowering of arterial pressure by clonidine did not significantly change baseline vasopressin, but facilitated osmotically induced vasopressin secretion.

Sympathetic nervous system and control of blood pressure during natural behaviour.

The role of the sympathetic nervous system in generating behaviourally linked blood pressure (BP) responses was investigated in awake rats instrumented for chronic intra-arterial BP recording. All data from the recording sessions were digitalized and processed by a computer. Frequency interval histograms of behaviourally associated changes of BP and heart rate (HR) were generated. 6-Hydroxydopamine (100 and 200 mg/kg intravenously) was used for chemosympathectomy. In the intact rats (n = 8) three different frequency histograms of mean BP values for three behavioural groupings were generated (from lowest to highest average values): (1) resting, (2) exploring-grooming and (3) eating-drinking. Chemosympathectomy (n = 5) abolished this order of BP changes; mean BP did not rise from rest to other behaviours, nor did it vary during different behaviours. It is concluded that the sympathetic nervous system is responsible for producing the changes in BP that are appropriate and characteristic of each behaviour in awake, unrestrained rats.

Fastigial nucleus stimulation and concurrent activation of cardiovascular receptors; differentiate effects on arterial pressure, heart rate and vasopressin release.

The integrated effects of stimulation of fastigial nucleus (FN) and of concurrent activation of baroreceptors on arterial pressure (AP), heart rate (HR) and vasopressin (VP) release in anaesthetized, paralysed, artificially ventilated rats were investigated. Stimulation of FN blocked the fall in AP and HR elicited by afferent vagal stimulation. It also abolished the atropine-sensitive bradycardia occurring at the peak of the stimulus-elicited pressor elevation in 6-hydroxydopamine treated rats. Sinoaortic denervation plus vagotomy left the cardiovascular responses to FN stimulus unmodified but facilitated FN elicited VP secretion. Vagotomy alone was ineffective. After high spinal cord transection more VP than in the intact condition was secreted after FN stimulation: simultaneous afferent vagal stimulation did not affect the facilitated VP release. Therefore FN stimulation can inhibit the reflex effects on AP and HR from baroreceptors, while the high-(but not the low-) pressure receptors can partly inhibit the VP release elicited by FN stimulation.

Regulation of vasopressin release in moderately severe essential hypertension.

Vasopressin plasma concentrations have been measured in two groups of subjects, 13 moderate essential hypertensive patients without target organ damage and eight control normotensive subjects, before and after the assumption of the upright position, and intravenous infusions of hypotonic saline (0.45% NaCl, 0.25 ml kg-1 min-1 for 1 h) and hypertonic saline (100 mmol NaCl in 50 ml). Plasma vasopressin in recumbent baseline conditions was not significantly different in the two groups. Upright posture and hypertonic challenge augmented, while hypotonic saline reduced plasma vasopressin levels, which were not significantly different between the two groups. Plasma renin activity increased in the upright position, was reduced by administration of hypotonic saline and unaffected by hypertonic saline, with no differences between the hypertensives and normotensives. After hypertonic saline, urinary flow rate and urinary sodium excretion in the hypertensive group increased to values significantly (p less than 0.05) higher than in normotensive subjects. In conclusion our study excludes significant alteration of vasopressin regulation in moderate uncomplicated hypertension. In hypertensives although the response of vasopressin to an osmotic load is preserved, the data suggest that the renal handling of the osmotic load may be altered.

Fastigial stimulation releases vasopressin in amounts that elevate arterial pressure.

Electrical stimulation of the cerebellar fastigial nucleus (FN) in anesthetized, paralyzed, and artificially ventilated rat with a 10-s stimulus train (50 Hz) resulted in a stimulus-locked elevation in arterial pressure (AP) and heart rate, the fastigial pressor response (FPR). Blockade of autonomic effectors by chemosympathectomy (produced by treatment with 6-hydroxydopamine) combined with adrenalectomy, or by spinal cord transection at C1, abolished the FPR but unmasked an elevation of AP with longer latency (10-12 s) and duration (2-4 min), termed the residual FPR. The residual FPR was 1) abolished by midbrain transection, 2) blocked by administration of a specific antagonist of the vasopressor response to arginine vasopressin (AVP) [1,d(CH2)5Tyr(Me)AVP], and 3) was absent in homozygous and attenuated in heterozygous rats of the Brattleboro strain. FN stimulation elevated AVP threefold (from 13 +/- 1 to 38 +/- 8 pg/ml, P less than 0.02; n = 6) in intact rats and sevenfold in rats with combined chemosympathectomy and adrenalectomy (from 14 +/- 1 to 96 +/- 11 pg/ml, P less than 0.001; n = 9). Stimulation of the cerebellar FN can release AVP. In the absence of sympathoadrenal effectors, the amount so released is enhanced and capable of elevating AP.

Inhibitory influences from arterial baroreceptors on vasopressin release elicited by fastigial stimulation in rats.

Electrical stimulation of the fastigial nucleus in anesthetized, paralyzed, and artificially ventilated rats for 10 seconds (50 Hz) induced a stimulus-locked elevation of arterial pressure (the fastigial pressor response) and increased plasma vasopressin. Cervical spinal cord transection abolished the stimulus-locked fastigial pressor response and augmented the vasopressin response to a 10-fold increase (19 +/- 1 to 188 +/- 58 pg/ml, P less than 0.05; n = 8). Grading the pressor elevations occurring during the fastigial nucleus stimulus changed the amounts of vasopressin released in the same animal: acute adrenalectomy and chemosympathectomy by guanethidine reduced the magnitude of the fastigial pressor response and facilitated the vasopressin release to fastigial nucleus stimulation (intact: 52 +/- 11 pg/ml; after adrenalectomy and chemosympathectomy, 254 +/- 73 pg/ml, P less than 0.05, n = 6). Subsequent intravenous administration of a bolus of phenylephrine to increase mean arterial pressure during fastigial nucleus stimulus, as in intact situation, reduced the vasopressin release (47 +/- 9 pg/ml). After sinoaortic denervation plus vagotomy, the fastigial pressor response was preserved; however, vasopressin still increased 11-fold (from 11 +/- 1 to 126 +/- 23 pg/ml, P less than 0.01, n = 8). Vagotomy alone did not affect the vasopressin resting level nor the 4-fold increase in response to fastigial nucleus stimulation. Therefore, stimulus-locked elevations of arterial pressure oppose, by reflex mechanisms mediated through baroreceptors, but do not prevent the release of vasopressin elicited by stimulation of the fastigial nucleus.

Cardiovascular changes during spontaneous micturition in conscious cats.

The hemodynamic changes occurring during spontaneous micturition were recorded in conscious cats. Arterial blood pressure was continuously measured by chronically implanted arterial catheter, heart rate (HR) by a cardiotachometer, and cardiac output (CO), superior mesenteric (MF), renal (RF), and external iliac blood flows (IF) by chronically implanted electromagnetic flow probes. Spontaneous micturition was accompanied by little change in mean arterial pressure (-9.7 +/- 0.7%), but by a marked decrease in HR (-49.0 +/- 1.2%) and CO (-28.6 +/- 2.5%), and therefore by a marked decrease in total peripheral conductance (-21.0 +/- 3.5%). Visceral and hindlimb blood flows were markedly reduced during micturition (MF, -34.7 +/- 2.1%; RF, -22.6 +/- 1.5%; and IF, -48.7 +/- 1.5%, respectively) due to a marked reduction in regional conductances in both these areas. The vasomotor changes in the regional circulations were prevented by local sympathectomy. Thus spontaneous micturition is associated with marked changes in cardiac function and systemic circulation. Cardiac output is decreased, but diffuse nervous systemic vasoconstriction compensates for this and provides maintenance of arterial blood pressure level.

Form and magnitude of beta-sympathetic and parasympathetic influences on pulse transit time.

In this study, we examined autonomic influences on pulse transit time measured from the R-wave of the electrocardiogram (R-PTT). Six subjects received three doses each of isoproterenol and atropine. Isoproterenol produced a significant linear decrease in R-PTT, a significant linear increase in heart rate (HR), and a significant linear decrease in diastolic blood pressure (DBP). Atropine produced a significant linear decrease in R-PTT and significant linear increases in HR and DBP. The R-PTT shortening effect of isoproterenol may reflect positive inotropic effects of beta-sympathetic myocardial stimulation. The R-PTT shortening effect of atropine may reflect reduction of parasympathetic inhibition of ventricular myocardial activity. However, possible vascular contributions to these effects remain to be determined. Nonetheless, the results encourage further examination of R-PTT in research concerning autonomic regulation of cardiovascular activity.

Role of sinoaortic reflexes in hemodynamic patterns of natural defense behaviors in the cat.

To evaluate whether sinoaortic afferents contribute to the hemodynamic pattern of fighting, cardiovascular changes associated with fighting were studied in cats before and after sinoaortic denervation. Sinoaortic denervation exaggerates the decrease in heart rate, cardiac output, and arterial pressure during immobile confrontation (hissing, staring but no movement). During nonsupportive fighting (fighting with forelimbs while lying on one side) and supportive fighting ( fighting while standing on four feet) sinoaortic denervation reduces the increase in heart rate and cardiac output, minimizes the mesenteric vasoconstriction, induces a fall in arterial blood pressure, but does not affect iliac vasoconstriction or vasodilatation. The hemodynamic pattern of fighting is similarly changed by temporary inactivation of carotid sinus baroreflexes by common carotid occlusion as by chronic section of sinoaortic nerves. It is concluded that sinoaortic reflexes play an important role in the cardiovascular patterns accompanying natural fighting. They favor cardiac action and allow a marked visceral vasoconstriction to occur, thus minimizing or preventing a fall in blood pressure during emotional behavior.

Vasopressin release and water metabolism in patients with cirrhosis.

Water retention is a complication in many patients with cirrhosis, usually attributed to excessive release of arginine vasopressin. To investigate the responsiveness of arginine vasopressin to osmotic and non-osmotic stimuli and its relationship to free water excretion, we studied 19 patients with cirrhosis under three different conditions: 45 min with legs raised to 60 degrees, to expand the central blood volume; infusion of 1000 ml of 0.45% saline solution to reduce plasma osmolality; and rapid injection of 50 ml of 2 M NaCl to increase plasma osmolality. Both expansion of central blood volume and decrease of plasma osmolality significantly reduced plasma vasopressin levels (from 2.1 +/- 0.6 to 1.39 +/- 0.3 pg/ml, p < 0.04; and from 1.09 +/- 0.25 to 0.41 +/- 0.13 pg/ml, p < 0.0001). The changes in free water excretion differentiated two subgroups of patients during each test: excretors and non-excretors. In the excretors, increased free water excretion was associated with suppressed vasopressin levels (below 0.5 pg/ml) and normal renal function. In the non-excretors, inability to improve free water excretion was associated with high vasopressin levels or with reduced distal delivery of the glomerular filtrate, except in some cases where vasopressin levels had fallen below 0.5 pg/ml and renal function was normal. For these cases the presence of other vasopressin-independent antidiuretic mechanisms is conceivable. The injection of hypertonic saline solution caused significant rises in plasma osmolality (from 287 +/- 1.9 to 292 +/- 1.6 mmol/kg, p < 0.05) and in plasma vasopressin levels (from 1.13 +/- 0.29 to 2.86 +/- 0.52 pg/ml, p < 0.05). These results suggest that vasopressin release in patients with cirrhosis is normally responsive to osmotic and non-osmotic stimuli, although our results show a lower theoretical osmolar threshold for suppression of vasopressin release in non-excretors than in excretors (276 vs 284 mmol/kg).

Fastigial stimulation in rats releases adrenomedullary catecholamines.

Electrical stimulation of the rostral fastigial nucleus (FN) in anesthetized, paralyzed, and artificially ventilated rats with a 10-s stimulus train elicited a stimulus-locked elevation of arterial pressure (AP) and heart rate (HR) (the fastigial pressor response, FPR) and elevated plasma catecholamines (CA) within 20 s from the onset of stimulus. Norepinephrine (NE) increased from 139 +/- 24 to 280 +/- 43 pg/ml (P less than 0.05, n = 8) and epinephrine (E) from 70 +/- 26 to 360 +/- 107 pg/ml (P less than 0.02, n = 8). Acute adrenalectomy increased basal plasma NE (362 +/- 108 pg/ml, P less than 0.05, n = 6) and reduced E (9 +/- 4 pg/ml, P less than 0.02, n = 6). The magnitude and duration of the FPR and the relative increase of NE were unchanged; however, the elevation of E was abolished. Chemosympathectomy, produced by 6-hydroxydopamine hydrobromide (100 mg/kg iv, 24 h before the experiment), lowered resting AP (from 122 +/- 2 to 77 +/- 1 mmHg, P less than 0.001) and NE (16 +/- 5 pg/ml, P less than 0.01), but not E. After chemosympathectomy, FN stimulation induced a pressor response of greater magnitude and longer latency and duration than in controls, increased NE 3.5-fold (from 16 +/- 5 to 56 +/- 14 pg/ml, P less than 0.05, n = 5) and E 9-fold (from 38 +/- 11 to 336 +/- 88, P less than 0.05, n = 5). The increases in CA were abolished by adrenalectomy. Chemosympathectomy shifted the pressor-dose-response curves of NE and E to the left; thus, the enhanced pressor response to FN stimulation after chemosympathectomy was possibly a consequence of supersensitivity to circulatory CA. Stimulation of cerebellar FN increased plasma CA, as a consequence of coexcitation of both neural and adrenomedullary components of the autonomic nervous system. However, in rats with intact sympathetic nerves the release of adrenomedullary CA did not contribute to the elevation in AP.