Biomedical subjects

R E Lang

Publications and source records attributed to R E Lang.

At least 109 records · Page 6Linked to original sources

PubMed1986

Differential modulation of the baroreceptor reflex by brain and plasma vasopressin.

Plasma vasopressin sensitizes the baroreceptor reflex, whereas vasopressin given into the cerebral ventricle overrides the baroreceptor reflex by means of sympathetic stimulation. To test the hypothesis that arginine vasopressin stimulates two different receptor subtypes (V1 and V2) in the central nervous system, we measured the baroreceptor reflex (change in pulse interval vs change in blood pressure) after administering methoxamine (10-300 micrograms/kg i.v.) in conscious rats. Animals were pretreated either with a V1 vasopressin receptor antagonist administered intravenously or intracerebroventricularly, or with a V2 receptor antagonist administered intravenously. The central V1 antagonist caused sensitization of the baroreceptor reflex, whereas the intravenous V2 antagonist attenuated it. The intravenous V1 vasopressin antagonist had no effect on baroreceptor reflex sensitivity. When the experiments were repeated in rats with hereditary diabetes insipidus, neither antagonist influenced the baroreceptor reflex. Volume expansion lowered circulating vasopressin levels and also attenuated the baroreceptor reflex--effects similar to those observed with the intravenous V2 antagonist. We conclude that vasopressin sensitizes the baroreceptor reflex through V2 receptors accessible from the blood and inhibits the reflex through V1 receptors in the brain that cannot be reached from the blood. These observations suggest a direct interaction between hormonal and neuronal vasopressin in cardiovascular control.

Animals↗

PubMed1986

Blood levels and renal effects of atrial natriuretic peptide in normal man.

Since mammalian atria were recently found to contain vasoactive and natriuretic peptides, we investigated the following in normal humans: plasma human atrial natriuretic peptide concentrations, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), urinary water and electrolyte excretion, blood pressure (BP), and catecholamine, antidiuretic hormone (ADH), angiotensin II, and aldosterone levels before, during, and after intravenous administration of the newly synthetized alpha-human atrial natriuretic peptide (alpha hANP). In 10 subjects alpha hANP given as an initial bolus of 50 micrograms followed by a 45-min maintenance infusion at 6.25 micrograms/min increased plasma alpha hANP from 58 +/- 12 to 625 +/- 87 (mean +/- SEM) pg/ml; caused an acute fall in diastolic BP (-12%, P less than 0.001) and a hemoconcentration (hematocrit +7%, P less than 0.01) not fully explained by a negative body fluid balance; increased GFR (+15%, P less than 0.05) despite unchanged or decreased ERPF (filtration fraction +37%, P less than 0.001); augmented (P less than 0.05- less than 0.001) urinary chloride (+317%), sodium (+224%), calcium (+158%), magnesium (+110%), phosphate excretion (+88%), and free water clearance (from -0.76 to +2.23 ml/min, P less than 0.001) with only little change in potassium excretion; and increased plasma norepinephrine (P less than 0.001) while plasma and urinary epinephrine and dopamine, and plasma ADH, angiotensin II, and aldosterone levels were unchanged. The magnitude and pattern of electrolyte and water excretion during alpha hANP infusion could not be accounted for by increased GFR alone. Therefore, in normal man, endogenous alpha hANP seems to circulate in blood. alpha hANP can cause a BP reduction and hemoconcentration which occur, at least in part, independently of diuresis and are accompanied by sympathetic activation. An increase in GFR that occurs in the presence of unchanged or even decreased total renal blood flow is an important but not sole mechanism of natriuresis and diuresis induced by alpha hANP in man.

Atrial Natriuretic Factor↗

PubMed1986

Comparison of plasma atrial natriuretic peptide levels in healthy children from birth to adolescence and in children with cardiac diseases.

An age-related dependence of plasma ANP levels was studied in 163 healthy children (94 boys, 69 girls) between the ages of day 1 and 16 yr. In neonates during the first 2-4 days of life, significantly higher plasma ANP plasma levels (range 129-356 pg/ml, mean 227) were found compared with older infants and children (p less than 0.001). Beyond the neonatal period through adolescence no significant difference in ANP concentrations could be found between the various age groups. Plasma ANP levels ranged between 2 and 109 pg/ml (mean 47) for all age groups after the newborn period. ANP levels were also determined in 15 adult volunteers and in arterial and venous cord blood of 16 healthy newborns, and concentrations were similar to those found in children. In addition, plasma ANP levels were measured in 40 children with various cardiac diseases; 22 of 40 patients exhibited ANP levels above the upper normal range seen in control children. Of these 22 patients all except two children revealed clinical signs of heart failure. In contrast 15 of 17 children without heart failure showed plasma ANP levels within the range of control children. ANP plasma levels ranged between 93 and 967 pg/ml (mean 284) in patients with heart failure and between 15 and 118 pg/ml (mean 57) in patients without heart failure, respectively. Increased ANP levels in neonates and cardiac patients may result from increased atrial distention and reflect a compensatory mechanism to improve cardiac function by reducing pre- and afterload.

Adolescent↗

PubMed1986

Plasma levels and cardiovascular, endocrine, and excretory effects of atrial natriuretic peptide during different sodium intakes in man.

Endogenous plasma concentrations of human atrial natriuretic peptide (alpha hANP) as well as effects of synthetic alpha hANP on some cardiovascular, endocrine, and renal excretory parameters were investigated in 10 normal subjects during sodium (Na+) intakes of 17, 140, and 310 mmol/day, respectively. Plasma hANP was slightly but not significantly higher after 5 days of normal or high sodium intake than after 5 days of low sodium intake [54 +/- 13, 46 +/- 8, and 37 +/- 5 (mean +/- SEM) pg/ml, respectively]. alpha hANP infused at 0.1 microgram/kg X min during all Na+ intakes produced a similar fall in diastolic blood pressure (P less than 0.001) and rise in heart rate (P less than 0.001), a comparable percent increase in plasma norepinephrine (P less than 0.001), and a reduction in plasma cortisol and aldosterone (P less than 0.01-0.001) despite raised renin activity (P less than 0.05-0.001) and unchanged plasma electrolytes. alpha hANP-induced plasma volume contraction, diuresis, and natriuresis were greater during high than low Na+ intake (P less than 0.01-0.001). Therefore, in normal man different Na+ intakes are accompanied by marked modifications in renal excretory responsiveness to alpha hANP. Regardless of sodium intake, alpha hANP can promote BP reduction and hemoconcentration, elicit reflex (?) sympathetic activation, and depress basal circulating aldosterone and cortisol levels in the face of an activated renin system.

Adult↗

PubMed1986

Depressor effects and release of atrial natriuretic peptide during norepinephrine or angiotensin II infusion in man.

Alpha-human atrial natriuretic peptide (alpha hANP) is the major circulating form of ANP in man. The potential of synthetic alpha hANP to antagonize the pressor action of norepinephrine (NE) or angiotensin II (AII) and a possible influence of NE or AII pressor infusions on circulating immunoreactive ANP (irANP) were investigated in 14 normal young subjects. After titration of doses to increase mean blood pressure by about 20 mm Hg, NE or AII was infused at a constant rate for 110 min. Mean blood pressure (BP) was similar during NE and AII infusions [109 +/- 4 (+/- SEM) and 108 +/- 3 mm Hg, respectively]. However, synthetic alpha hANP injected in stepwise increasing doses of 10, 40, and 75 micrograms caused significantly greater (P less than 0.001) BP reductions during NE infusion. alpha hANP lowered BP progressively from 147/91 +/- 5/3 to 136/70 +/- 5/3 mm Hg during NE infusion (P less than 0.001) and only minimally from 133/96 +/- 3/3 to 132/89 +/- 4/4 during AII infusion. Heart rate was elevated more (P less than 0.01) after alpha hANP injection during NE infusion. Endogenous plasma irANP increased significantly after 20 min of NE or AII pressor infusion (P less than 0.01 and P less than 0.05, respectively); this rise was more pronounced (P less than 0.05) during NE (from 25 +/- 2 to 80 +/- 20 pg/ml) than during AII (from 21 +/- 3 to 31 +/- 3 pg/ml) infusion. These findings suggest that alpha hANP interacted preferentially with noradrenergic as compared to angiotensinergic BP control. Conversely, for a given rise in BP, NE elicited a greater rise in circulating irANP.

Adult↗

PubMed1986

Atrial natriuretic peptide and volume changes in children.

The effect of volume changes on the plasma concentration of atrial natriuretic peptide (ANP) was investigated. In children with chronic renal failure predialysis plasma ANP was higher as compared to normal children and decreased significantly during hemodialysis. The decrease in plasma ANP correlated with body weight reduction. On the other hand, increase in plasma volume by infusion of albumin in children with nephrotic syndrome caused significant rise in plasma ANP and an increased natriuresis. Our data demonstrate that an expanded extracellular fluid volume and/or plasma volume appears to be a major stimulus for the release in ANP in children.

Adolescent↗

PubMed1986

Atriopeptin III kinetics and pharmacodynamics in normal and anephric rats.

To elucidate the disposition of atriopeptin III in plasma we performed experiments in normal and anephric rats. Bolus, i.v. atriopeptin III (250 ng) was given after which the rats were decapitated at 30-sec intervals. The half-life of atriopeptin III in normal rats was 26.5 sec, the volume of distribution was 352 ml and the plasma clearance was 500 ml/min. In anephric rats the half-life was 56.8 sec, the volume of distribution was 345 ml and the plasma clearance was 206 ml/min. In other rats atriopeptin III was given and urine was collected simultaneously. No atriopeptin III could be measured in the urine. We gave 0.0, 0.067, 0.125, 0.25, 0.5 and 1.0 ng/kg of bolus atriopeptin III to normal rats and measured effects on blood pressure, heart rate and plasma concentration at 30 sec, the time at which maximum effect on blood pressure occurred. Dose, change in blood pressure and plasma concentration were correlated. Heart rate increased, but not in a dose-dependent fashion. We conclude that atriopeptin III is cleared from rat plasma rapidly and that the kidneys account for 59% of its elimination by degradation rather than excretion. Because the effect of atriopeptin III on blood pressure is concentration-dependent, the transient changes exerted by atriopeptin III may be related to its rapid disappearance from plasma.

Animals↗

PubMed1986

Plasma atrial natriuretic peptide values in cardiac disease.

The plasma concentrations of atrial natriuretic peptides (ANP) were measured during cardiac catheterization in 137 patients with heart disease. Atrial natriuretic peptides were elevated in all types of cardiac disease investigated, including valve disease, coronary heart disease and cardiomyopathy. The highest plasma ANP concentrations were found in patients with the most marked impairment of ventricular function and mitral valve disease. In patients with coronary heart disease, a significant, direct linear correlation was found between left ventricular filling pressure and plasma ANP concentrations (r = 0.42, P less than 0.001). Similarly, in patients with cardiomyopathy, a linear relationship was found between mean pulmonary artery pressure and plasma ANP concentration (r = 0.80, P less than 0.01). These observations suggest that measurement of ANP may be of value as a non-invasive humoral marker in the diagnosis of various cardiac diseases.

Atrial Natriuretic Factor↗

PubMed1986

Pressure dependent release of atrial natriuretic peptide (ANP) in patients with chronic cardiac diseases: does it reset?

In patients with chronic cardiac disease plasma concentrations of atrial natriuretic peptide are elevated. The close relationships obtained between right (and/or left) atrial pressure and the peptide concentrations suggest a non-resetting phenomenon of the pressure induced release mechanism in the presence of a maintained responsiveness to acute stimuli.

Atrial Natriuretic Factor↗

PubMed1986

Pathomorphological study of the endocrine heart in various cardiovascular diseases.

Tissue of the endocrine heart was examined from patients undergoing open heart surgery for aorto-coronary bypass and correction of valve and septum diseases. The right auricular myoendocrine cells were studied with immunohistochemistry and electron microscopy for cardiac hormones (cardiodilatin = CDD-99-126, which is identical to alpha-human atrial natriuretic polypeptide = alpha-hANP). Furthermore, the pre- and postoperative blood samples were analysed by radioimmunoassay (RIA) combined with high pressure liquid chromatography (HPLC) to determine the plasma concentration and the molecular forms of circulating CDD-99-126/alpha-hANP. The results show that, depending on the status of the patient, differing quantities of CDD-IR (cardiodilatin immunoreactivity) are detected in the myoendocrine cells. This is also confirmed by the granularity of myoendocrine cells, as seen in the electron microscope. The ACB (aorto-coronary bypass) patients with normotonia exhibit, as a rule, the status of a normal endocrine heart. In mitral valve diseases, particularly in the combined vitia, prominent autophagolytic changes in myoendocrine cells are frequently seen. Pre- and postoperative blood shows only one circulating form of cardiodilatin which exhibits the characteristics of the 28 amino acid residues containing molecule CDD-99-126/alpha-hANP. The postoperative CDD content of blood plasma tends to decrease mainly in patients with successful treatment.

Atrial Natriuretic Factor↗

PubMed1986

Plasma kinetics of synthetic alpha-human atrial natriuretic peptide in man.

Atrial natriuretic peptides (ANPs) circulate in the blood stream and may modulate the regulation of blood pressure, sodium-fluid volume state and renal function. In man, alpha-human ANP (alpha hANP) is probably the major circulating form of ANP. To evaluate its plasma kinetics, we studied in 7 healthy men plasma alpha hANP concentrations under basal conditions and at short intervals during and up to 40 min after discontinuation of a 45-min constant alpha hANP infusion at a rate of 0.1 microgram/min/kg. From basal levels averaging 75 +/- 18 pg/ml (mean +/- SEM), plasma alpha hANP concentrations increased to 1,185 +/- 321 and 1,117 +/- 175 pg/ml at 30 and 40 min during the alpha hANP infusion, respectively. After discontinuing the latter, plasma alpha hANP decreased rapidly, following first-order kinetics, with a plasma half-life of 3.2 +/- 0.4 min. This finding is in line with the brief effects of intravenously applied alpha hANP and suggests that this system may be designed for rapid minute-to-minute adjustments.

Adult↗

PubMed1986

Relationships between haemodynamic parameters and concentrations of atrial natriuretic peptide in human plasma.

Plasma concentrations of the atrial natriuretic peptide (ANP) were measured during cardiac catheterization in 289 patients with heart disease. It was elevated in all types of cardiac disease investigated, irrespective of the nature and duration of the disease. Close relationships were observed between the elevated ANP concentrations and the increased right and/or left atrial pressure. Further increments in ANP concentration were measured during exercise in direct response to the rise in mean pulmonary artery pressure. Thus, ANP concentrations may be regarded as a non-invasive marker of the haemodynamic burden in cardiac disease.

Atrial Natriuretic Factor↗

PubMed1986

Regulation of atrial natriuretic peptide secretion.

To evaluate the role of the autonomic nervous system in the regulation of atrial natriuretic peptide (ANP) secretion, the secretory responses of isolated perfused rat hearts to adrenaline and acetylcholine were studied. Infusion of adrenaline produced a dose-dependent rise in heart rate and contractile force associated with a marked increase in perfusate ANP immunoreactivity. The ANP response was almost completely abolished by the alpha-adrenoceptor antagonist phentolamine (10(-6)) and attenuated by the beta-adrenoceptor antagonist metoprolol (10(-5)). Thus, both alpha- and beta-adrenoceptors may mediate the adrenaline effect on ANP release. Perfusion of the isolated heart with 10(-6) or 10(-5) acetylcholine resulted in a short rise in hormone release followed by a gradual decline. The negative ionotropic and chronotropic effects of acetylcholine and the rise in ANP induced by acetylcholine were blocked by atropine, suggesting that a muscarinic receptor is involved. The finding that both adrenaline and acetylcholine alter ANP secretion rate points to the participation of autonomic nerves in the regulation of ANP release from atrial cardiocytes.

Acetylcholine↗

PubMed1986

Antihypertensive action and inhibition of tissue converting enzyme (CE) by three prodrug CE inhibitors, enalapril, ramipril and perindopril in stroke-prone spontaneously hypertensive rats.

The active diacids of the new converting enzyme (CE) inhibitors ramipril and perindopril proved to possess a similar inhibitory potency against rat plasma CE in vitro. Both diacids were more active than enalaprilic acid or captopril. In stroke-prone spontaneously hypertensive rats (SHRSP) chronic oral treatment for 2 weeks with enalapril (30 mg/kg per day), ramipril or perindopril (each 1 mg/kg normalized blood pressure. The CE inhibitor-induced changes in parameters of the plasma renin-angiotensin system [angiotensin I (ANG I), angiotensin II (ANG II), PRC and CE activity] followed the expected pattern, but were not quantitatively related to the antihypertensive action of the three CE inhibitors. Four weeks of oral equi-dose treatment with the three CE inhibitors (10 mg/kg per day) inhibited tissue CE activity in various organs including kidney, heart, vascular wall and brain. Ramipril and perindopril lowered blood pressure and tissue CE activity more potently than enalapril did. These results are consistent with the hypothesis that CE inhibition in tissue with subsequent local reduction of ANG II synthesis may contribute to the antihypertensive mechanisms of CE inhibitors.

Angiotensin II↗

PubMed1986

Effect of angiotensin I converting enzyme inhibition on circulating atrial natriuretic peptide in humans.

We investigated the effects of inhibition of angiotensin II (ANG II) formation with an ANG I converting enzyme inhibitor, namely Enalapril, on circulating levels of atrial natriuretic peptide (ANP). Seven normal volunteers received a low sodium diet in order to stimulate the renin-angiotensin system (period I). Subsequently, subjects maintained their low dietary sodium intake and received Enalapril perorally (period II). Each study period lasted for 6 days. Results indicated that subjects maintained a low dietary sodium intake with expected changes of the renin system before and during ANG I converting enzyme inhibition. Enalapril elicited a substantial fall in circulating ANP levels in six of the seven subjects studied. The causes of this change will have to be established but may possibly relate to hemodynamic consequences of Enalapril.

Adult↗

PubMed1986

[Antihypertensive action and inhibition of tissue conversion enzyme by ramipril, perindopril and enalapril in the spontaneously hypertensive rat (SHRSP)].

Ramipril and perindopril, the active diacids of two new converting enzyme (CE) inhibitors proved to possess a similar inhibitory potency against rat plasma CE in vitro. These diacid compounds were more active than enalaprilic acid or captopril. In stroke-prone spontaneously hypertensive rats (SHRSP) chronic oral treatment for two weeks with enalapril (30 mg/kg per day), ramipril or perindopril (each 1 mg/kg per day) normalized blood pressure. The CE inhibitor-induced changes in parameters of the plasma renin-angiotensin system (angiotensin I, angiotensin II, PRC, CE activity) followed the expected pattern, but were not quantitatively related to the antihypertensive action of the three inhibitors. Four weeks of oral equi-dose treatment with the three CE inhibitors (10 mg/kg per day) inhibited tissue CE activity in various organs including kidney, heart, vascular wall and brain. Ramipril and perindopril lowered blood pressure and tissue CE activity more potently than enalapril. These results confirm the hypothesis that CE inhibition in tissue with subsequent local reduction of ANG II synthesis may contribute to the antihypertensive mechanisms of CE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1985

Atrial natriuretic peptide secretion: synergistic effect of phorbol ester and A23187.

To investigate the role of inositol phospholipid turnover in the atrial natriuretic peptide (ANP) secretion, the secretory responses from isolated perfused rat hearts to the ionophore, A23187, and the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), alone or in combination, were studied. A23187 induced a sharp increase in ANP secretion, whereas TPA caused a slowly progressive increase in secretion rate. 4 alpha-phorbol-12,13-didecanoate, which lacks the ability to activate protein kinase C, had no effect on ANP secretion. The combination of A23187 and TPA stimulated ANP secretion higher than the calculated additive value for each agent. The synergistic effect of the agents suggests a role of calcium-activated protein kinase C in ANP secretion from atrial cardiocytes.

Animals↗

PubMed1985

Concomitant increase in plasma atrial natriuretic peptide and cyclic GMP during volume loading.

To investigate the effects of fluid expansion on endogenous atrial natriuretic peptide (ANP) and cyclic 3',5'-guanosine monophosphate (cGMP), four male volunteers were studied before, during and after intravasal volume loading. Volume expansion was performed by intravenous infusion of 2,000 ml isotonic saline solution within 30 min. Mean plasma ANP levels increased 2.5-fold from 31.2 pg/ml to 81.7 pg/ml 40 min after the start of infusion. Plasma cGMP levels paralleled the rise in ANP, showing a mean cGMP increment from 2.7 pmol/ml to a maximum of 8.2 pmol/ml. Both ANP and cGMP levels were back to basal levels 120 min after termination of the infusion. Stimulation of endogenous ANP release by volume loading suggests that ANP is involved in the regulation of fluid homeostasis in man. The parallel rise in plasma cGMP levels supports the idea that cGMP is a mediator for the effects of ANP.

Adult↗