Hypoventilation and apnoea induced by the substance P antagonist [D-Pro2,D-Trp7,9]-SP in the ventrolateral rat medulla.
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Animals↗
Biomedical subjects
J Hedner
Publications and source records attributed to J Hedner.
Differential haemodynamic effects of atrial natriuretic peptide (ANP) in normotensive and spontaneously hypertensive rats.
Central haemodynamic parameters and cardiac performance were measured in conscious spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) control rats after a 10-min infusion of rat ANP (103-125), 1 micrograms kg-1 min-1. Mean Arterial blood pressure (MAP) decreased by approximately 10% in both groups of rats. Heart rate (HR) increased slightly in both strains during the infusion. In the normotensive group the fall in MAP was due to a reduction in cardiac output (CO) while in the SHR there was a decrease in CO as well as in total peripheral resistance (TPR). The ANP infusion also reduced central blood volume (CBV) and stroke volume (SV) in both groups of rats. The reduction in CBV and CO was significantly more pronounced in the WKY strain. Left ventricular end diastolic pressure (LVEDP) and cardiac contractility (dP/dt) did not change while central venous pressure (CVP) was slightly decreased in the WKY group as a result of the ANP infusion. We conclude that ANP reduces MAP in normotensive animals by a reduction in CO. In the SHR a reduction in TPR also contributes to the fall in MAP. Atrial natriuretic peptide did not exert any negative inotropic effects, but the reduction of CO was due to an increased venous compliance.
Animals↗
Plasma atrial natriuretic peptide (ANP) and maternal hemodynamic changes during normal pregnancy.
Peripheral venous plasma concentrations of immunoreactive atrial natriuretic peptide (irANP) were studied longitudinally in 12 women at the 12th, 24th, and 36th week of pregnancy as well as 3-5 days and 3 months post partum. Serial measurements of maternal hemodynamics were performed simultaneously with blood sampling for irANP determination. With advancing pregnancy there were significant increases (p less than 0.001) in cardiac output, stroke volume and heart rate, while total peripheral vascular resistance decreased (p less than 0.001). All these changes were normalized 3 months post partum. Plasma irANP increased (p less than 0.05) from 23.2 +/- 1.3 pM/l at week 12 to 25.9 +/- 1.5 pM/l at week 36 of pregnancy, and fell significantly (p less than 0.01) to 20.5 +/- 1.1 pM/l 3 months post partum. Changes in plasma irANP appear to be related to changes in maternal central hemodynamics. The changes in ANP release probably represent one of several mechanisms that maintain circulatory and volume homeostasis during normal pregnancy.
Adult↗
beta-Casomorphins induce apnea and irregular breathing in adult rats and newborn rabbits.
Bovine beta-casomorphin, beta-casomorphin, morphiceptin or morphine were administered systemically (i.v. or i.p.) and intracerebroventricularly (lateral or IVth ventricles) to anesthetized adult rats and preterm newborn rabbits. All agents caused dose-related depressions of respiratory frequency and tidal volume. Morphiceptin and beta-casomorphin were approximately equipotent to morphine while beta-casomorphin was 10 times as potent after intracerebroventricular injection. The beta-casomorphins decreased inspiratory drive and prolonged the expiratory phase by delaying the setpoint for inspiration. A respiratory depression could be elicited by systemic administration of morphiceptin but not by beta-casomorphin or beta-casomorphin. All ventilatory effects induced by the beta-casomorphins could be readily reversed or prevented by naloxone. Intracerebroventricular but not intraperitoneal injection of beta-casomorphin depressed ventilation in preterm newborn rabbits in a similar pattern with apnoic periods to that seen in the adult rats. In addition, an irregular breathing pattern was elicited. Thus, the bovine beta-casomorphins possess potent central respiratory depressive effects. However, after systemic administration, only morphiceptin which is more metabolically stable induced a shortlasting effect on ventilation in adult rats.
Amino Acid Sequence↗
Plasma atrial natriuretic peptide and blood pressure during chronic salt loading in spontaneously hypertensive rats with right atrial appendectomy.
Spontaneously hypertensive rats (SHR) were subjected to right atrial appendectomy (ATRX) or sham operated. Five days after this procedure the rats were put on tap water or 1.5% NaCl as drinking water for 1 week. The blood pressure (carotid artery), 24 hours urinary sodium and kalium excretion, plasma levels of immunoreactive atrial natriuretic peptide (ir-ANP) and the rise in plasma ir-ANP concentrations after an acute volume expansion by homologous whole blood (10%) were evaluated after 1 week on the different diets. At the start of the dietary period the rise in plasma ir-ANP values was blunted in ATRX rats. After 1 week the salt loaded animals excreted tenfold more sodium than control rats. At this time basal ir-ANP values in plasma were not significantly influenced by the ATRX and/or the high salt diet but the rise in plasma ir-ANP concentrations to acute volume expansion was blunted in the salt loaded rats. However, the basal blood pressure was not influenced by the salt diet and/or the ATRX. These data do not support the notion that an alleged deficiency in ANP release mechanisms in the SHR is a major determinant for the blood pressure development in this rat strain.
Animals↗
Changes in plasma atrial natriuretic peptide--immunoreactivity in patients undergoing coronary artery bypass graft placements.
Plasma atrial natriuretic peptide immunoreactivity (IrANP) was measured before, during, and after cardiopulmonary bypass for coronary artery bypass graft placement. Eight subjects scheduled for elective operation had in the premedicated preoperative state slightly elevated IrANP compared to controls. Neither induction of anesthesia with a high dose narcotic/non-depolarising relaxant/diazepam technique nor cardiopulmonary bypass changed IrANP significantly. Mixed venous and arterial IrANP increased immediately after discontinuing bypass, and remained elevated 1 h later. Because ANPs affect peripheral resistance as well as urinary sodium loss, the post-bypass elevations in these peptides may contribute to cardiovascular and diuretic effects after cardiopulmonary bypass.
Anesthesia↗
ANP--a cardiac hormone and a putative central neurotransmitter.
Isolation, purification and determination of the amino acid sequences of biologically active peptides were performed in 1983-84 by several groups. By that time the existence of such a humoral diuretic/natriuretic factor had been proposed for many years. The main, and perhaps the only, circulating form of atrial natriuretic peptide (ANP) is a 28 amino acid peptide structure with a disulphide bridge. This peptide is distributed mainly peripherally in the right and left cardiac atria. Smaller amounts are found in neonatal cardiac ventricles as well as in autonomic ganglia. In the central nervous system, high concentrations are found in hypothalamus, while lower concentrations are found in midbrain and brain stem regions. The amino acid sequence of ANP in the brain may be shorter than the form originating from cardiac atria. A 1 126 amino acid prohormone is present in granulae of atrial myocytes. After atrial distention the circulating 28 amino acid form is cleaved off. The main actions of this hormone include a diuretic/natriuretic effect, relaxation of vascular smooth muscle, and inhibition of basal or stimulated aldosterone secretion from the adrenal cortex. In the central nervous system, ANP has antidipsogenic actions, decreases salt appetite and lowers blood pressure. ANP may be of pathophysiological importance in several cardiovascular disorders such as congestive heart failure, paroxysmal supraventricular tachycardia and possibly also arterial hypertension. ANP seems to be a circulating hormone as well as putative neurotransmitter with important regulatory actions on salt and water homeostasis as well as blood pressure regulation.
Adrenal Cortex↗
Increased plasma levels of atrial natriuretic peptide (ANP) in patients with paroxysmal supraventricular tachyarrhythmias.
Atrial natriuretic peptide (ANP) is a cardiac hormone originating from atrial cardiocytes. It seems to be involved in the regulatory control of circulating volume and vascular tone. Plasma immunoreactive atrial natriuretic peptide (IrANP) was investigated in 22 patients with paroxysmal supraventricular tachyarrhythmia (16 with atrial fibrillation, 4 with atrial flutter, one with a Wolf-Parkinson-White syndrome (WPW) and one with atrial tachycardia). During the aute attack, IrANP was significantly increased (125.3 +/- 11.4 pmol/l) compared to samples obtained during convalescence (55.9 +/- 4.7 pmol/l). Heart rate (HR) was 144 +/- 4.3 beats/min during the arrhythmia and 75 +/- 2.6 during convalescence. The reduction of IrANP in plasma from the acute attack of tachycardia to follow-up was significantly related to the reduction of HR (p less than 0.05). Irrespective of type of paroxysmal supraventricular tachyarrhythmia, 50% of the patients experienced polyuria during the attack. This symptom was more frequent in younger patients with a shorter duration of tachycardia. Polyuria patients had a higher HR during the attack of supraventricular tachycardia. Even though polyuria was not always found in the patients with the highest IrANP values, the symptom was associated with significantly higher concentrations of IrANP in plasma compared to the non-polyuria group. We conclude that IrANP is increased in plasma during acute attacks of paroxysmal supraventricular tachycardia. Furthermore, the polyuria frequently associated with this condition may partly be due to excess release of ANP from cardiac myocytes.
Adult↗
Significant relationship between renin suppression and atrial natriuretic peptide (alpha-hANP) during volume loading in hypertensive men.
We have studied eight men with moderate hypertension to determine the atrial natriuretic peptide (alpha-hANP) response to acute volume expansion. Rapid infusion of 1,000 ml 0.9% saline (10-20 min) caused an increase in central venous pressure (4.7 +/- 1.6 cmH2O) while blood pressure and pulse pressure (arterial baroreceptor load) did not change. Stroke volume and heart rate were not affected by the volume load but plasma renin activity (PRA) was significantly suppressed (from 0.83 +/- 0.14 to 0.68 +/- 0.34 microgram AI I/ml-h; p less than 0.01). A significant hemodilution was also observed. Renal sodium excretion was significantly increased. Arterial alpha-hANP increased significantly from 21.1 +/- 6.1 to 30.5 +/- 4.0 pmol/l (p less than 0.02) during volume expansion. There was a significant correlation between corrected plasma volume increase (urine volume subtracted from the infused volume) and alpha-hANP plasma elevation (r = 0.78; p less than 0.05). There was also a significant negative correlation between changes alpha-hANP and PRA (r = -0.78, p less than 0.05). We conclude that only moderate volume loading in human hypertensives is a mechanism for increase in plasma alpha-hANP levels. The significant negative correlation between changes in alpha-hANP and PRA suggests that alpha-hANP may be the humoral factor at least partly responsible for suppression of renin in hypertensive man. Since increased fluid volume also affects sympathetic renal efferents as well as vasopressin secretion, our observed relationship between volume load and renin may well be related also to such mechanisms.
Adult↗
Effects of chronic salt loading on plasma atrial natriuretic peptide (ANP) in the spontaneously hypertensive rat.
Plasma concentrations of immunoreactive atrial natriuretic peptide (ANP) was measured in spontaneously hypertensive rats (SHR) during chronic salt loading (1.5% NaCl in drinking water). During the 3-week experimental period mean arterial blood pressure, heart rate, urinary sodium excretion and body weight was assessed in salt-loaded as well as in control rats. The sodium excretion was more than 10-fold increased in the rats on the high salt diet. The plasma ANP concentration was significantly increased only 24 h after the start of the high salt intake. Thereafter plasma ANP concentrations were not significantly different from values obtained in control rats. The blood pressure was significantly increased after 3 weeks on the high salt diet. At the end of the 3-week experimental period the rats were subjected to a 10 and 20% acute volume expansion with homologous whole blood. During this intervention the increase in plasma ANP concentrations was blunted in the high salt rats compared to the control group. It is concluded that during chronic salt loading in SHR there is an initial rise in plasma ANP levels and that other hormonal and neuronal systems are more important in the long term maintenance of fluid and electrolyte balance.
Animals↗
Respiratory stimulant effects by TRH into the mesencephalic region in the rat.
Thyrotropin-releasing hormone (TRH) has previously been found to have a potent respiratory stimulant effect following intracerebroventricular administration. One part of the respiratory response, the shortening of inspiratory time, seems to be elicited from the raphe obscurus in the medulla. The prominent tachypnoea however is not elicited after local injections in the medullary region. In the present paper a micro-injection technique was employed to study respiratory actions of TRH in lightly anaesthetized rats kept in a whole body plethysmograph. Thyrotropin-releasing hormone in a dose of 100 ng per 0.5 microliter was found to induce an immediate tachypnoea after injections into the region of the interpeduncular nucleus of the midbrain. No effects on systemic circulation were seen. More rostral or dorsal sites of injection were without effect. The localization of the sites responsible for respiratory stimulation corresponds to the reticular activating system where electrical stimulation induces hyperventilation in cats. The tachypnoea might be closely related to the well known arousal effects of TRH.
Animals↗
Acute volume expansion as a physiological stimulus for the release of atrial natriuretic peptides in the rat.
The concentration of immunoreactive atrial natriuretic peptide(s) (ANP) was measured in normovolemic conscious rats and 15 min after 10% and 20% blood volume expansion. A 20% blood volume expansion caused a 2-fold increase in plasma ANP. While plasma ANP increased linearly, atrial levels of ANP remained unaltered. The increase in plasma ANP parallelled increases of central blood volume and central venous pressure. It is concluded that acute blood volume expansion is a major physiological stimulus for the release of atrial natriuretic peptides into the circulation.
Animals↗
Characterization of the antinociceptive effects of some adenosine analogues in the rat.
The antinociceptive effects of the stable adenosine analogues N6-phenylisopropyladenosine (L-PIA), N6-cyclohexyladenosine (CHA) and 5'-N-ethylcarboxamidoadenosine (NECA) were investigated in conscious rats using cutaneous thermal tests (hot plate and tail flick). Subcutaneous administration of the adenosine analogues induced a dose-dependent antinociceptive response for all agents. However, NECA was approximately 15 times more potent than PIA and CHA. Approximately the same potency order and response was seen when the adenosine analogues were administered intrathecally at the lumbar level. By this route of administration, the adenosine analogues were approximately 10-20 times more potent than after S.C. administration. Intracerebroventricular administration (lateral ventricles), however, induced a variable response, in most cases a slight hyperalgesia. The nonspecific adenosine antagonist theophylline (S.C.) rapidly reduced the antinociceptive effect induced by PIA (S.C.) but enprofylline, a bronchodilating xanthine with low ability to antagonize adenosine did not influence PIA-induced antinociception. It is concluded that stable adenosine analogues and presumably adenosine itself have potent antinociceptive effects via specific adenosine receptors in the rat. The effects seem to be mediated mainly by a spinal mechanism of action.
Adenosine↗
Increased plasma levels of atrial natriuretic peptide in patients with congestive heart failure.
Atrial natriuretic peptide (ANP) is a recently discovered hormone, originating from atrial myocardium. The peptide (or family of peptides) induces potent diuretic/natriuretic, vasorelaxing and aldosterone inhibitory effects. We have investigated plasma concentrations of immunoreactive ANP in 10 patients with congestive heart failure (CHF). Mean plasma ANP concentrations were more than three times higher in CHF patients than in a matched control group. High plasma ANP concentrations in pathophysiological conditions with a high preload combined with salt and water retention is consistent with a physiological role of this hormone to correct hypervolemia by causing natriuresis and diuresis. It is concluded that ANP homeostasis is altered in patients with CHF and that this hormone may be of importance in the pathophysiology of CHF.
Atrial Natriuretic Factor↗
Increase in plasma atrial natriuretic peptides during acute volume expansion in hypertensive man.
A new hormonal system originating from cardiac atria has recently been discovered. These peptide hormones have important functions in the regulation of blood volume and fluid homeostasis. We have measured plasma concentrations of atrial natriuretic peptides (ANP) in two patients during acute volume expansion. ANP concentrations increased in relation to an increase in right atrial pressure, and significant diuresis/natriuresis was observed. We conclude that hormonal as well as neuronal mechanisms are activated by acute volume loading in man.
Atenolol↗
Release of atrial natriuretic peptide (alpha-hANP) and circulating noradrenaline in relation to central and renal hemodynamics and sodium output during acute volume load in hypertensive and normotensive men.
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Adult↗
The diuretic effect of atrial natriuretic peptide (ANP) is dependent on dopaminergic activation.
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Animals↗
Developmental variations in CSF monoamine metabolites during childhood.
Cerebrospinal (CSF) fluid content of the stable metabolites homovanillic acid, 3-methoxy-4-hydroxyphenyl glycol and 5-hydroxyindoleacetic acid were measured in 19 children without neurological disease known to alter CSF monoamine metabolites. The CSF levels of all three metabolites were found to be up 6 times higher in early infancy compared to the values during adolescence. The levels decreased in a logarithmic fashion, and adult values (approx. 25-50 ng/ml) were reached at 3-5 years of age. Two different interpretations of the findings are discussed: (1) a higher release or turnover of central serotonin and catecholamine metabolites during early postnatal age, or (2) lower clearance of the stable acid metabolites from CSF during infancy due to relatively immature active transport mechanisms.
Adolescent↗