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Biomedical subjects

R E Lang

Publications and source records attributed to R E Lang.

At least 91 records · Page 5Linked to original sources
PubMed1987

Regulation of release and function of neuropeptides in the heart.

The mechanisms regulating the release of enkephalins and neuropeptide Y (NPY) from cardiac nerve fibers were studied in the isolated perfused guinea pig heart. Besides NPY, all peptides of the proenkephalin B family were found to be stored in the adrenergic nerve endings. Following electrical stimulation of the accelerans nerve, but not of the vagus nerve, the peptides were detected in the perfusate indicating their release from sympathetic nerve endings. The release of both enkephalins and NPY was enhanced by phentolamine or yohimbine and diminished by cocaine. Thus, sympathetic amines may directly regulate the release of their cotransmitters via a presynaptic alpha-adrenergic mechanism. Enkephalins exerted a weak negative inotropic effect that appeared to be mediated by opioid receptors of the kappa type. Neuropeptide Y is a potent vasoconstrictor and may be involved in the regulation of coronary blood flow.

Adrenergic Fibers↗
PubMed1987

Increased plasma cyclic guanosine monophosphate concentrations in children with high levels of circulating atrial natriuretic peptide.

Simultaneous measurements of plasma atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (GMP) concentrations were performed in children with various forms of cardiac diseases (n = 22) and in control children (n = 29). In healthy children, plasma ANP and cyclic GMP levels ranged between 2.4 and 98.0 (mean 45.8) pg/mL and 0.2 to 2.8 (mean 1.40) pmol/mL, respectively. In children with cardiac diseases, plasma ANP (26.0 to 499.7 [mean 188.7] pg/mL) and cyclic GMP (0.2 to 6.0 [mean 2.9] pmol/mL) levels were significantly higher than in control children (both P less than .0001). There was a linear correlation between the two values in children with cardiac diseases (P less than .01). Because the effects of ANP to target tissues are mediated by cyclic GMP, cyclic GMP appears to be a marker for the cellular responses to ANP. The increased cyclic GMP levels in children with cardiac diseases indicate that ANP exerts its effects on target organs also in states of chronically enhanced ANP levels.

Adolescent↗
PubMed1987

Effects of atrial natriuretic factor in rats with renal insufficiency.

To test the effect of exogenous atrial natriuretic factor (ANF) on the kidney function of rats with chronic renal insufficiency, we examined the responses to bolus infusions of atriopeptin III in two models of renal insufficiency, namely, nephrosclerosis and glomerulonephritis. Hypertensive Dahl S rats receiving a high (8%) NaCl diet for 12 weeks, and rats with anti-glomerular basement membrane nephritis, both of which had glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) less than half those of respective control rats, exhibited similar relative increases In GFR and ERPF in response to atriopeptin III as did controls. Natriuresis, diuresis, and decreased blood pressure were as prominent in rats with either form of renal disease as in control rats. Rats receiving high NaCl intake, irrespective of renal function, had relatively exaggerated responses compared with rats receiving a normal NaCl diet. We conclude that rats with chronic renal insufficiency of diverse causes respond briskly to ANF despite presumed hyperperfused and hyperfiltering nephrons. Thus, diseased kidneys exhibit substantial renal functional "reserve." The renal response to ANF appears to be influenced by NaCl intake in both normal animals and those with renal insufficiency.

Animals↗
PubMed1987

Brain angiotensin II: localization and possible functions.

The results of biochemical, immunohistochemical and autoradiographic studies have led to the description of the endogenous brain angiotensin II system as a highly localized network of angiotensin II-containing cell bodies and fibers 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 of brain angiotensin II in the control of these homeostatic functions. In particular, brain angiotensin II may function to help maintaining adequate tissue perfusion to vital parts of the body at times, when body fluid and cardiovascular homeostasis are jeopardized. In addition, there is evidence that brain angiotensin II may participate in the control of hormone release from the anterior and posterior pituitary gland, regulation of body temperature and the processing of learning contents. Future research may profitably be directed towards an exact functional characterization of central angiotensinergic pathways as well as an detailed analysis of the mechanisms that underly central angiotensin II-induced responses.

Angiotensin II↗
PubMed1987

The effects of orchidectomy and testosterone replacement therapy on plasma and brain oxytocin in normal rats.

In male rats, two-week orchidectomy induced a significant increase in the pituitary content of oxytocin-immunoreactivity and a significant fall in its hypothalamic concentration, without detectable changes in plasma. Testosterone replacement therapy in castrated animals abolished the stimulant effect of orchidectomy on pituitary accumulation of oxytocin. The present study demonstrates an inhibitory effect of testicular androgens on oxytocin release. These results and previous observations suggest that the neurohypophysial hormone oxytocin may play a role in male reproductive system.

Animals↗
PubMed1986

The central pressor actions of substance P are inhibited by GABA.

The influence of GABA-ergic stimulation on the centrally evoked pressor and tachycardic responses to substance P (SP) was investigated in conscious rats. Intracerebroventricular (i.c.v.) pretreatment with the potent GABA agonist muscimol attenuated the pressor responses to i.c.v. administered SP in a dose-dependent and reversible fashion. Inhibition was maximal 5-60 min after muscimol injection and lasted up to 3 h. In contrast, the increases in heart rate in response to i.c.v. administered SP were not consistently inhibited by muscimol. Central pretreatment with muscimol prevented the increase of plasma adrenaline but not of plasma noradrenaline in response to i.c.v. administered SP. Our results demonstrate that the GABA-ergic system can exert an inhibitory control on pathways mediating the central pressor actions of SP. The selective inhibition of adrenaline secretion by muscimol implies that suppression of sympathetic outflow to the adrenal gland may be involved as an important mechanism. In addition, our findings point to a dissociation between pathways mediating the pressor and tachycardic effects of SP.

Animals↗
PubMed1986

The phorbol ester induced atrial natriuretic peptide secretion is stimulated by forskolin and Bay K8644 and inhibited by 8-bromo-cyclic GMP.

The role of intracellular signals in the regulation of atrial natriuretic peptide (ANP) release was studied using the isolated perfused rat heart. The phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), known to activate the protein kinase C pathway, produced a dose-dependent increase in perfusate ANP immunoreactivity. Bay k8644, a putative calcium channel activator, and forskolin, which stimulates adenylate cyclase, induced a sustained increase in ANP secretory rate. TPA in combination with either Bay k8644 or forskolin induced higher ANP secretion than the calculated additive value for each agent. 8-bromo-cyclic GMP and sodium nitroprusside, when given alone, had no effect on ANP secretion, but delayed the TPA-stimulated increase in perfusate ANP. ANP secretion appears therefore to be mediated both by the phosphoinositide and the cAMP system, whereas the cGMP pathway may be inhibitory.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Effect of salt loading and salt deprivation on the vasopressin and oxytocin content of the median eminence and the neural lobe in adrenalectomized rats.

In adrenalectomized rats the influence of salt loading or salt deprivation on the vasopressin and oxytocin content of the median eminence (ME) and the neural lobe (NL) was studied by means of various methods: morphometric and microphotometric analysis of aldehyde fuchsin-stained sections of ME and NL; immunohistochemical demonstration of neurophysin, oxytocin, and vasopressin in the ME and in the NL; radioimmunological measurement of oxytocin and vasopressin in the ME and in the NL. Adrenalectomy in salt-substituted rats raised the vasopressin content of the outer layer of the ME (OLME) but had no influence on the amount of vasopressin in the inner layer of the ME and in the NL. Osmotic stimulation of adrenalectomized rats by hypertonic saline markedly diminished vasopressin and oxytocin in the inner layer of the ME and in the NL but did not, or only slightly reduced vasopressin in the OLME. Withdrawal of salt supplementation in adrenalectomized rats resulted in a decrease of plasma sodium and plasma volume. It did not change the vasopressin or oxytocin content of the inner layer of the ME and of the NL, but it was correlated with a decrease of vasopressin in the OLME. The present findings may suggest that vasopressin in the OLME is involved in salt and/or volume regulation by influencing the hypophysial-adrenal axis.

Adrenalectomy↗
PubMed1986

Increase in atrial pressure releases atrial natriuretic peptide from isolated perfused rat hearts.

To elucidate the mechanism involved in the release of atrial natriuretic peptide, we modified the isolated perfused rat heart preparation to permit a step-wise increase in right atrial tension. Perfusate was introduced into the right atrium through the superior vena cava and was collected via the pulmonary artery. Right atrial pressure was manipulated by changing the perfusion rate. Perfusate from the pulmonary artery was collected in 1-min-fractions, extracted, and assayed for atrial natriuretic peptide like immunoreactivity (ANP-li). The basal rate of ANP-li release at an atrial pressure of 1.41 +/- 0.31 mm Hg was 964 +/- 144 pg/min (n = 11). As right atrial pressure was increased (range 0.4-4.5 mm Hg), a linear correlation (r = 0.85, P less than 0.001) was observed between the change in ANP-li release and the change in atrial pressure. High pressure liquid chromatography revealed that the major fraction in the perfusate had the same elution time than alpha-rANP. This peak fraction, as well as synthetic atriopeptin III, caused a dose-dependent relaxation in rat aortic strips that had been subjected to contraction with norepinephrine. Further, it corresponded exactly to the material we previously identified in rat plasma. These results suggest that atrial distension is involved in the release of ANP. In addition, ANP is released per se, as the active peptide.

Animals↗
PubMed1986

Role of atrial natriuretic peptide in sodium homeostasis in premature infants.

To examine the possible involvement of atrial natriuretic peptide (ANP) in sodium homeostasis in premature infants, two groups of low birth weight infants with different dietary sodium regimens were studied. Sodium balance and plasma concentration of ANP were measured at weekly intervals for 5 weeks. At 1 week of age the study was started by dividing infants into two groups, group 1 with low and group 2 with increased sodium intake. Mean plasma concentrations of ANP were 47.7 +/- 7.6 and 51.4 +/- 9.5 fmol/ml, respectively. A steady decrease in plasma ANP concentration to 18.8 +/- 2.9 fmol/ml was observed in infants with sodium intake 1.5 mmol/kg/d (group 1), which was related to the decrease in serum sodium concentration in this group. In contrast, supplementation with NaCl 4.6 mmol/kg/d (group 2) was associated with a 30% increase in plasma ANP concentration, significantly different (P less than 0.025) from that in infants not given supplement, and was also higher than the values in full-term neonates. Our data suggest that altered sodium homeostasis induces regulatory changes in plasma ANP levels. ANP may provide a sensitive and important hormonal system for the control of sodium balance, even in premature neonates.

Atrial Natriuretic Factor↗
PubMed1986

Atrial natriuretic factor determinations and chronic sodium homeostasis.

To examine the physiological role of atrial natriuretic factor (ANF) in the maintenance of sodium homeostasis under various conditions, we performed experiments in rats across a wide range of sodium intake, in rats with chronic renal insufficiency at extremes of sodium intake, and in rats given desoxycorticosterone acetate. After three weeks of a very low sodium diet, regular diet, or regular diet plus 1% saline as drinking water, no difference in plasma values of immunoreactive atrial natriuretic factor (IR-ANF) were identified, while rats at the lowest level of sodium intake had elevated atrial values. Normal rats, and rats with 5/6 nephrectomy has plasma values of IR-ANF which were no different irrespective of their sodium intake, nor were atrial values in these rats different. Although mineralocorticoid "escape" could be documented by changes in urine sodium excretion, neither plasma nor atrial IR-ANF values showed differences either at 24 or 72 hr after "escape". The data are consistent with previous observations that ANF serves the purpose of affecting rapid adjustments to large alterations in circulating fluid volume. Chronic high sodium intake, adaptation to renal insufficiency, and adjustment to the effect of mineralocorticoid do not appear to be associated with increased circulating plasma concentrations of IR-ANF.

Animals↗
PubMed1986

Plasma arginine-vasopressin levels during infusion of synthetic atrial natriuretic peptide on different sodium intakes in man.

The mechanisms involved in the diuretic action of the recently discovered group of atrial natriuretic peptides (ANP) are not entirely clear. To determine whether the diuresis and the changes in blood pressure produced by alpha-human ANP (alpha-hANP) involved a concomitant modification of circulating arginine-vasopressin (arg-VP), we evaluated the effects of synthetic alpha-hANP on plasma alpha-hANP, arg-VP, electrolytes, protein, haematocrit, blood pressure and urinary sodium and water excretion in 10 normal subjects on daily sodium intakes of 16, 140 and 310 mmol, respectively. Plasma alpha-hANP levels before and during a 45-min alpha-hANP infusion (0.09 micrograms/kg per min) tended to be slightly, though not significantly, higher on 'normal' or high sodium intake than on low sodium intake. Alpha-human ANP produced a fall in diastolic blood pressure (P less than 0.001) and to a lesser extent mean blood pressure, and a rise in heart rate (P less than 0.001) at all levels of sodium intake. The induction of diuresis, natriuresis and plasma volume contraction caused by alpha-hANP was greater on a high sodium intake than on 'normal' or low sodium intakes (P less than 0.001). Plasma arg-VP concentrations were lower (P less than 0.05) on a high than on a low sodium intake, but were not altered by an alpha-hANP infusion. The data indicate that in healthy humans circulating arg-VP may tend to decrease in response to a high salt diet. However, marked changes in plasma alpha-hANP concentrations have, regardless of sodium intake, no relevant influence on circulating arg-VP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Differential actions of neuronal and hormonal vasopressin on blood pressure and baroreceptor reflex sensitivity in rats.

The central cardiovascular actions of arginine vasopressin (AVP) and the role of this peptide in the modulation of baroreceptor reflex (BRR) sensitivity were investigated in conscious, chronically instrumented rats. Intracerebroventricular (i.c.v.) injections of AVP (1-100 ng) produced dose-dependent pressor effects together with increases in heart rate, splanchnic, and renal sympathetic nerve activity and a reduction of mesenteric blood flow. These responses were prevented by i.c.v. pretreatment with a V1-AVP receptor antagonist. Furthermore, the central pressor effects of AVP were abolished by peripheral alpha-adrenoceptor blockade with phentolamine. In contrast to the i.c.v. injections, intravenous (i.v.) or intracarotid injections of AVP produced pressor responses accompanied by bradycardia and a decrease in sympathetic nerve activity. Intracerebroventricular pretreatment with a V1-AVP receptor antagonist shifted the slope of the BRR curve (increases in pulse interval plotted against increases in systolic blood pressure in response to i.v. methoxamine) toward higher sensitivity, whereas i.v. pretreatment with a V2-AVP receptor antagonist shifted the slope of the BRR curve toward lower sensitivity of the reflex. These findings suggest that central (neuronal) AVP, by acting on V1-AVP receptors in the brain, participates in central pressor mechanisms, activates the sympathetic nervous system, and desensitizes the BRR. Conversely, circulating (hormonal) AVP can sensitize the BRR by acting on V2-AVP receptors accessible from the blood. Our data provide evidence pointing to a direct interaction between the neuronal and the hormonal axis of the AVP system within cardiovascular control.

Animals↗
PubMed1986

Tissue converting enzyme and cardiovascular actions of converting enzyme inhibitors.

The discovery of tissue renin-angiotensin systems (RAS) in organs controlling the cardiovascular system has opened new perspectives for our understanding of the cardiovascular actions of converting enzyme (CE) inhibitors. Direct application of CE inhibitors to the brain and heart entails distinct cardiovascular effects. Systemic treatment with CE inhibitors leads not only to an inhibition of the plasma RAS, but it also inhibits tissue CE in various organs and reduces local angiotensin II concentrations. Evidence is presented that oral CE inhibitor treatment markedly influences organ function of the heart, brain, and vascular wall independently of the plasma RAS. These findings are compatible with the concept that tissue CE inhibition contributes to the beneficial actions of CE inhibitors in cardiovascular disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Effect of urapidil, clonidine, and prazosin on sympathetic tone in conscious rats.

To test the hypothesis that the hypotensive action of urapidil is in part related to a direct action on the brain, the central (intracerebroventricular) and peripheral (intravenous) effects of urapidil were studied and compared with those obtained with clonidine and prazosin. All studies were conducted in conscious, chronically instrumented stroke-prone spontaneously hypertensive rats (SHRSP). Efferent sympathetic nervous system activity was estimated by means of a bipolar electrode implanted on the splanchnic nerve. Only clonidine, administered intracerebroventricularly and intravenously, decreased sympathetic nerve activity. Urapidil and prazosin either did not affect sympathetic nerve activity after central administration or increased it after peripheral administration at low and high doses, respectively. Centrally administered urapidil and prazosin lowered blood pressure but also blocked the response to intravenously administered phenylephrine; this result suggests a peripheral effect. Centrally administered urapidil decreased heart rate. Urapidil given either intracerebroventricularly or into the cisterna magna had no influence on baroreceptor responses. Intravenous infusions of urapidil and prazosin in sufficient doses to lower blood pressure in spontaneously hypertensive rats by 50 mm Hg completely blocked the actions of phenylephrine. These data suggest that in conscious SHRSP urapidil lowers blood pressure through peripheral blockade of alpha 1-adrenergic receptors rather than by means of central sympathetic suppression. In this regard urapidil resembles prazosin rather than clonidine; however, the effect of urapidil on heart rate is consistent with a central mode of action.

Animals↗