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Biomedical subjects

R E Lang

Publications and source records attributed to R E Lang.

At least 73 records · Page 4Linked to original sources
PubMed1988

Influence of diurnal rhythm, posture and right atrial size on plasma atrial natriuretic peptide levels.

A diurnal rhythm of plasma atrial natriuretic peptide (ANP) and cyclic 3'5'guanosine monophosphate (cGMP) was found in nine healthy adult volunteers. Significantly higher levels of both parameters were found in the morning (8 a.m.) than later during the day and night (p less than 0.05). Different postures had only a little influence on plasma ANP and cGMP levels in seven healthy adult volunteers using a tilt table. Tilted from supine into upright, head-down (-20 degrees) and then again into supine posture, significant differences of both parameters were only found between levels shortly after the end of the upright posture and those at the end of the head-down posture (p less than 0.05). Furthermore, in infants with various congenital heart diseases (n = 19) and control infants (n = 35) the right atrial area was determined by two-dimensional echocardiography and related to plasma ANP levels. Out of 19 infants with cardiac disease, 11 showed an enlarged right atrial area (i.e. above the 95th percentile in the range of control infants). All these 11 infants also had higher plasma ANP levels (range 115-670 pg/ml) than the healthy infants (range 5-98 pg/ml). These data support the assumption that atrial wall distension seems to be a stimulus for ANP release.

Adult↗
PubMed1988

[The renin-angiotensin system: systemic and local function].

The renin-angiotensin system (RAS) has long been known as a hormonal system, which is important for the maintenance of volume homeostasis, and which contributes under certain circumstances to the pathogenesis of hypertension and cardiac failure. More recent findings have demonstrated that the individual components of this system can also be synthesized locally in tissue, e.g. in the brain, the vascular wall, the kidney, the adrenals, and the heart. Although the role of locally generated angiotensin within cardiovascular- and body volume regulation needs to be further investigated, it has already become clear that the mechanism of action of drugs interfering with the RAS is not confined to the circulating RAS, but also includes an interaction with local renin-angiotensin systems. These agents, particularly the converting enzyme inhibitors, have proved to be indispensible tools for elucidating the function of local renin-angiotensin systems, in addition to being therapeutically useful in the treatment of cardiovascular diseases.

Angiotensin II↗
PubMed1988

Measurement and characterization of angiotensin peptides in plasma.

We report a method for the extraction of angiotensin peptides from plasma with a mixture of acetone, 1 mol/L HCl, and water (40/1/5 by vol). The method is highly reproducible for the measurement of angiotensin I and angiotensin II in small sample volumes, with analytical recoveries of about 80% for both peptides. We investigated the influence of sample handling and found a standard procedure for blood collection, plasma preparation, and extraction was essential. The method was used to measure angiotensin I and II in rat and human plasma. In rat plasma, the mean (+/- SEM) concentrations of angiotensin I and angiotensin II were determined to be 67 (+/- 8) and 14 (+/- 1) pmol/L (n = 10), respectively. Neither angiotensin I nor angiotensin II was detectable 24 h after bilateral nephrectomy. Acute oral administration of the converting-enzyme inhibitor ramipril caused a significant increase of angiotensin I from 85 (+/- 6) to 257 (+/- 33) pmol/L (n = 10; P less than 0.001) and a significant decrease of angiotensin II from 12 (+/- 1) to 7 (+/- 0.4) pmol/L in rat plasma (n = 9; P less than 0.001). In human plasma, angiotensin I and angiotensin II values of 21 (+/- 1) and 6.6 (+/- 0.5) pmol/L (n = 10) were found. A single oral dose of the diuretic furosemide increased angiotensin I significantly from 21 (+/- 1) to 32 (+/- 1.7) pmol/L (n = 5); P less than 0.001), whereas angiotensin II remained unchanged, 6.6 (+/- 0.5) vs 6.4 (+/- 0.4) pmol/L (n = 5). Extracted peptides could be identified as [IIe5]-angiotensin I and [IIe5]-angiotensin II by HPLC in combination with specific radioimmunoassays for angiotensin I and angiotensin II.

Adult↗
PubMed1988

[Significance of atrial natriuretic peptide in heart failure: experimental findings].

We investigated the role of atrial natriuretic peptide (ANP) in a rat model of chronic heart failure (CHF) (coronary ligation) by four different studies: (1) stimulation of secretion of ANP by volume loading, (2) infusion of 1 micrograms/min of rat ANP (99-126), (3) correlations of pressure measurements of right atrium (RAP) and LVEDP versus plasma ANP levels and ANP mRNS versus infarct size, (4) blocking endogenous plasma levels of ANP with monoclonal ANP antibody. In severe CHF, volume loading did not exert a significant increase in plasma ANP, in contrast to moderate CHF or to normal animals. Infusion of ANP reduced RAP and LVEDP without significant increase in renal blood flow (radioactive microspheres) in rats with severe cardiac failure, in contrast to normal animals. A close relationship was found between LVEDP and atrial plasma levels. After injection of ANP antibody, filling pressures and systemic vascular resistance increased, indicating that removal of ANP may enhance arterial vasoconstriction or elevated endogenous ANP to exert a vasodilatory action in severe heart failure. Nevertheless, the cardiocirculatory effects, primarily on renal blood flow, appear to be limited.

Animals↗
PubMed1988

Nicotine-induced release of noradrenaline and neuropeptide Y in guinea pig heart.

The effect of nicotine on the release of noradrenaline and neuropeptide Y was investigated in isolated perfused guinea pig hearts (Langendorff technique). Endogenous noradrenaline, dihydroxyphenylglycol (both determined by high pressure liquid chromatography) and neuropeptide Y (determined by radioimmunoassay) were measured in the coronary venous effluent following the addition of nicotine to the perfusate. Nicotine (2 microM to 2 mM) dose-dependently increased both noradrenaline and neuropeptide Y overflow, and the release of both transmitters was closely correlated (r = 0.81). Despite ongoing nicotine administration noradrenaline and neuropeptide Y levels returned to basal values within 6 min of continuous nicotine administration indicating rapid tachyphylaxis to the effect of nicotine. The nicotine-induced release of noradrenaline and neuropeptide Y required the presence of extracellular calcium, and the release of both substances was suppressed by hexamethonium or by low concentrations of the inhibitors of the neuronal noradrenaline uptake (uptake1) desipramine and nisoxetine. Nicotine did not result in a significant release of the noradrenaline metabolite dihydroxyphenylglycol which was utilized as an indicator of free axoplasmic amine levels. The close correlation between noradrenaline and neuropeptide Y release, its calcium dependence, and the lack of dihydroxyphenylglycol overflow are in agreement with the concept of a common and exocytotic release of noradrenaline and neuropeptide Y induced by nicotine.

Animals↗
PubMed1987

Effect of converting enzyme inhibitors on tissue converting enzyme and angiotensin II: therapeutic implications.

Local tissue renin-angiotensin systems have recently been discovered in various organs, and evidence is accumulating that inhibition of these local renin-angiotensin systems may contribute to the actions of converting enzyme (CE) inhibitors. Measurements of CE activity and angiotensin II concentrations revealed that after oral administration of CE inhibitors, CE was inhibited not only in lung vascular endothelium and blood, but also in the heart, kidney, vascular wall, brain and other organs. The functional significance of tissue CE inhibition is suggested first by the antihypertensive effect of brain CE inhibition in spontaneously hypertensive rats, second by the concomitant persistence of blood pressure decrease and CE inhibition in vascular wall and kidney after long-term oral CE inhibitor treatment and third by ex vivo experiments demonstrating marked effects of oral CE inhibitor pretreatment on cardiac function in isolated rat hearts. Local inhibition of tissue renin-angiotensin systems may be an important factor involved in the beneficial effects of CE inhibitors in such cardiovascular diseases as arterial hypertension, congestive heart failure and cardiac arrhythmias.

Administration, Oral↗
PubMed1987

Atrial natriuretic peptide and other vasoactive hormones in nephrotic syndrome.

Plasma levels of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), renin activity (PRA), aldosterone (PA), catecholamines and urinary prostaglandins (PG), as well as renal function were measured in children in the edematous state of the nephrotic syndrome before and after infusion of human serum albumin. Before albumin infusion, plasma levels of AVP, PRA, PA and noradrenaline (NA) and urinary excretion of PGE2, PGE-Met, PGF2 alpha were elevated. The mean value of plasma ANP was in the normal range. Albumin infusion produced a 36% increase in the calculated plasma volume. It was associated with a fivefold rise in the plasma level of ANP (31.6 +/- 22.6 vs. 151.4 +/- 52 fmol/ml mean, SD), and a significant fall in the levels of PRA, AVP, PA, and NA. Similarly, urinary concentration of PGE2, PGE-Met and PGF2 alpha fell. Urine flow, GFR, UNaV, FENa, and COsm increased significantly, while CH2O remained unchanged. The diuresis, natriuresis and GFR correlated with the level of plasma ANP, while urinary sodium excretion did not correlate with PA or NA levels. These findings suggest that ANP plays an important role in albumin induced natriuresis in children with nephrotic syndrome.

Adolescent↗
PubMed1987

The renin-angiotensin system in the central control of blood pressure.

The results of biochemical, immunohistochemical and autoradiographic studies led to the description of the endogenous brain angiotensin II system as a highly localized network of angiotensin II-containing cell bodies and fibres as well as characteristic sites with high angiotensin II-receptor density. The specific localization of this system predominantly within limbic, hypothalamic and brain stem structures that are known to be involved in central cardiovascular regulation and the control of volume homeostasis, suggests a possible functional role for brain angiotensin II in the control of these homeostatic functions. A role for brain angiotensin II in the central control of blood pressure is further supported by physiological and pharmacological experiments that demonstrate characteristic central angiotensin-induced cardiovascular responses. However, it should be kept in mind that the mechanisms mediating these responses (e.g. sympathetic activation, vasopressin release), as well as the exact functional role of endogenously synthesized angiotensin II in specific brain areas, are not yet completely understood. Pathophysiologically, there is evidence that an activated brain renin angiotensin system may participate in the development and maintenance of primary hypertension.

Angiotensin II↗
PubMed1987

Release and regulation of atrial natriuretic peptide (ANP).

Mammalian atrial cardiocytes synthesize and secrete a hormone called atrial natriuretic peptide (ANP), which causes natriuresis, diuresis and inhibition of smooth muscle contraction, aldosterone and renin release. Volume loading, vasoconstrictor agents, immersion in water, atrial tachycardia and high salt diets have been reported to increase the release of cardiac ANP, thereby suggesting that the peptide is released in response to an increase in atrial pressure. That stretch is an important stimulus for ANP release is also suggested by clinical studies demonstrating a direct correlation between secretion rate and atrial pressure. The experiments using isolated perfused rat heart provide direct evidence that distension of the right atrium stimulates the release of ANP. Pharmacological studies in the isolated heart point to roles of cytosolic calcium, the phosphoinositide system and the cyclic AMP pathway in the regulation of ANP release. The concentration of calcium in heart muscle cells, in addition to the length of the muscle fibers, depends on many factors such as the action of humoral substances, cardiac nerve activity and heart rate, which may all contribute to the regulation of ANP secretion.

Acetylcholine↗
PubMed1987

Atrial natriuretic factor in sodium-sensitive and sodium-resistant Dahl rats.

We tested the hypothesis that atrial natriuretic factor (ANF) may play a role in the development of hypertension in salt-sensitive Dahl (S) rats as compared to normotensive salt-resistant Dahl (R) rats. We measured immunoreactive ANF in plasma and atria of the inbred (JR) strain of Dahl S and R rats receiving 0.9 or 8% NaCl diets for up to 8 weeks. We also tested the effect of acute volume expansion on plasma and atrial ANF values in rats receiving the 0.9% salt diet. In addition, we examined the effects of exogenous ANF in the form of atriopeptin III given as intravenous bolus infusion at both levels of salt intake. We found no difference in plasma and atrial values between S and R rats irrespective of salt intake. The S and R rats showed a similar, five- to sevenfold increase of plasma ANF in response to acute saline expansion. Finally, we were unable to demonstrate differences between S and R rats in response to atriopeptin III with respect to transient decreases in blood pressure, and pronounced increases in glomerular filtration rate (GFR), renal blood flow or natriuresis. These results do not reveal appreciable changes in the ANF system of Dahl S rats either before or after onset of hypertension when compared to normotensive R rats. Therefore, our findings do not support the notion that ANF is important in the development or maintenance of chronic salt-induced hypertension in S rats.

Anesthesia↗
PubMed1987

Blood pressure, electrolyte and adrenal responses in swim-trained hypertensive rats.

In order to test the effect of aerobic training on blood pressure, and to examine the putative mechanisms involved, stroke-prone spontaneously hypertensive rats (SHR-SP), borderline hypertensive rats (BHR), and Wistar-Kyoto control rats (WKY) were swim-trained for up to 1.5 h twice-daily for 22 weeks. The BHR were F1 back-cross SHR-SP, WKY. A training effect was observed in the trained rats compared to controls, as demonstrated by slower heart rates, heavier hearts and increased cytochrome oxidase activity in their skeletal muscle. Trained SHR-SP and BHR had significantly lower blood pressures at the end of the intervention period (approximately 10 mmHg) compared to controls. Acute increases in blood pressure with swimming were less in trained than in untrained rats. Trained rats had higher extracellular sodium values than untrained rats. Further, trained SHR-SP and BHR had lower intra-erythrocyte sodium values than controls. Increases in corticosterone, epinephrine and norepinephrine with swimming were less in trained rats than in controls. We conclude that exercise conditioning ameliorates hypertension in rats. The mechanism may involve an effect on cation transmembrane transport, as well as decreased, adrenosympathetic tone. Moreover, these effects may be related.

Adaptation, Physiological↗
PubMed1987

Atrial natriuretic peptide: a new factor in blood pressure control.

The hypothesis of a natriuretic factor-originally an intriguing possibility and now an experimentally documented reality-has occupied the minds of scientists for more than 30 years. It has attracted not only experts in salt and water metabolism but also those interested in hypertension, because of the well known link between sodium homeostasis and blood pressure regulation. There are at least two distinct types of natriuretic substances: one is an inhibitor of the Na+K+ATPase and has been proposed to contribute to a rise in blood pressure; the other, now isolated from atrial tissue, is vasodilatory, natriuretic, diuretic, and has been demonstrated to decrease blood pressure. Our knowledge of regulation and function of this ANP has increased rapidly since its detection. Its role in blood pressure regulation is now fairly well understood. As depicted in Fig. 1, both synthesis and release of ANP are induced by atrial and ventricular wall stretch. In hypertension, distension of the left atrium and ventricle may be of particular importance for ANP release. The endocrine function of myocardial cells is stimulated in response to wall stretch in the ventricle. ANP is synthesized and stored as a 126 amino acid prohormone. Enzymatic processing of this prohormone to the circulating forms ANP 1-98 and ANP 99-126 takes place within the myoendocrine cells. The biological effects of ANP 1-98 are as yet unknown. ANP 99-126 acts at multiple sites to reduce blood pressure. One may distinguish between acute and more chronic effects. The acute effects include shift of fluid to the extravascular compartment and vasorelaxation. This shift is indicated by the rapidly developing rise in haematocrit, which is observed in intact as well as in nephrectomized rats and therefore not due to diuresis alone. The reduction of blood volume in addition to an increase in venous capacitance may be responsible for the reduced cardiac output. The latter may cause a reflex activation of the sympathetic nervous system and an increase in peripheral resistance, thereby overriding the vasodilator effects of the peptide. ANP appears to have a 'de-pressor' effect rather than a direct vasodilator effect. A lowering of peripheral resistance in response to ANP is not observed in normotensives, but is readily seen in at least certain forms of hypertension associated with an increased vascular tone. This most likely explains the discrepancy in the haemodynamic responses to ANP in normotensives and hypertensives.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Tissue renin-angiotensin systems: focus on the heart.

Recent findings support the existence of independently functioning, local renin-angiotensin systems in a number of tissues. The clinical importance that inhibitors of the renin-angiotensin system have gained in the treatment of hypertension and cardiac failure, as well as molecular biology data, suggest that a functional, tissue renin-angiotensin system is present in the heart. Using several experimental approaches we present evidence to support the existence and the possible physiopathological relevance of such a cardiac renin-angiotensin system. Tissue angiotensins were documented and quantified in different regions of the heart by high performance liquid chromatography combined with specific radio-immunoassay. Reduction of cardiac angiotensin after administration of converting enzyme inhibitors in nephrectomized animals indicates that these peptides are generated locally. Effects of converting enzyme inhibitors on angiotensin II-dependent facilitation of cardiac sympathetic tone further support this concept and emphasize the potential physiological role of a cardiac renin-angiotensin system. Further, direct evidence for local generation of angiotensin II in the myocardium is provided by assessment of the intracardiac conversion of angiotensin I to angiotensin II and by measurement of the activity of angiotensin converting enzyme in the heart.

Angiotensin II↗
PubMed1987

Influence of dopamine on atrial natriuretic peptide level in premature infants.

The role of dopamine (DA) in the activation and/or release of atrial natriuretic peptide (ANP) was investigated in 11 premature infants during the early postnatal period. Mean plasma concentration of ANP and free DA level before DA infusion was 252.6 +/- 210 fmol/ml, and 0.4 +/- 0.2 ng/ml, respectively. DA infusion in a dose of 2 micrograms/kg/min caused a rise in plasma free DA level to 59.7 +/- 21.5 ng/ml and a significant increase in GFR, diuresis, sodium excretion and fractional sodium excretion. The plasma concentration of ANP, however, remained unchanged (252.6 +/- 210.0 vs. 213 +/- 143.0 fmol/ml). Thus, our data failed to demonstrate a stimulatory effect of DA on ANP release in premature infants. The role of the high plasma concentration of ANP in preterm neonates immediately after birth has to be clarified.

Atrial Natriuretic Factor↗
PubMed1987

Neuropeptide Y inhibits renin release by a pertussis toxin-sensitive mechanism.

The effects of neuropeptide Y (NPY) were studied in the isolated rat kidney, which was perfused at constant perfusion pressure with a synthetic medium. In this preparation NPY produced concentration (1-100 nM)-dependent inhibition of renin release and vasoconstriction. In kidneys perfused at constant flow, inhibition of renin release by NPY was even more pronounced, excluding a flow-dependent washout effect. The simultaneous infusion of the calcium channel antagonist methoxyverapamil (2 microM) or of the calmodulin inhibitor calmidazolium (1 microM) did not prevent these effects of NPY, suggesting that calcium-dependent reactions are not primarily involved. Inhibition of renin release by NPY was also observed in tissue pieces prepared from the hydronephrotic rat kidney, in which tubular elements are lacking. This indicates that inhibition of renin release by NPY is not dependent on the presence of macula densa cells or on changes of intrarenal hemodynamics. In isolated kidneys from rats pretreated with pertussis toxin (2 micrograms/100 g ip) both effects of NPY, renal vasoconstriction and inhibition of renin release, were almost completely abolished. The pertussis toxin-sensitive factor mediating the effects of NPY is most likely the Ni-coupling protein of the adenylate cyclase complex. Accordingly, our data suggest that NPY induces renal vasoconstriction and inhibits renin release by inhibition of adenylate cyclase activity in vascular smooth muscle and renin-producing cells.

Adenylate Cyclase Toxin↗
PubMed1987

Plasma atrial natriuretic peptide levels in children with cardiac diseases: correlation with cGMP levels and haemodynamic parameters.

In children with various forms of cardiac diseases (aged 2 months to 16 years) significantly higher plasma atrial natriuretic peptide (ANP; range 36-680, median 247 pg/ml) and cyclic 3'5'-guanosine monophosphate (cGMP; range 0.2-46, median 8.2 pmol/ml) levels were found than in control children (p less than 0.0001). In control children (aged 4 months to 17 years) plasma ANP and cGMP levels were measured in the range of 2.4-98 pg/ml and of 0.2-2.8 pmol/ml, respectively. There was a linear correlation between the two parameters in children with cardiac diseases (r = 0.62, p less than 0.01). Children with elevated mean right atrial pressure (i.e., greater than 6 mm Hg) showed significantly higher plasma ANP levels than children with normal atrial pressure (p less than 0.01). However, there was only a weak linear correlation between mean right atrial pressure and plasma ANP levels (r = 0.48, p less than 0.01). Plasma ANP levels from right atrium, pulmonary artery, left atrium and left ventricle were significantly higher than those from vena cava (p less than 0.05). Analysis of ANP-like immunoreactive material by high performance liquid chromatography suggested that alpha-ANP is the major form of circulating ANP in blood of children with cardiac diseases.

Adolescent↗
PubMed1987

Tissue converting enzyme inhibition and cardiovascular effects of converting enzyme inhibitors.

Local renin-angiotensin systems have been described in organ controlling cardiovascular function. Following oral administration of converting enzyme (CE) inhibitors the enzyme was inhibited not only in lung vascular endothelium and blood, but also in the heart, kidney, vascular wall, brain and other organs. Evidence for a contribution of tissue CE inhibition to the cardiovascular actions of CE inhibitors is provided by the antihypertensive effect of brain CE inhibition in spontaneously hypertensive rats, by the concomitant persistence of blood pressure decrease and CE inhibition in vascular wall and kidney after chronic oral CE inhibitor treatment, and by the marked effects of oral CE inhibitor pretreatment on cardiac function in isolated rat hearts. Local inhibition of tissue renin-angiotensin systems may therefore be an important factor involved in the beneficial effects of CE inhibitors in cardiovascular diseases such as arterial hypertension, congestive heart failure, and cardiac arrhythmias.

Angiotensin-Converting Enzyme Inhibitors↗