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Biomedical subjects

R E Lang

Publications and source records attributed to R E Lang.

At least 55 records · Page 3Linked to original sources
PubMed1989

Demonstration of atrial natriuretic peptide/cardiodilatin (ANP/CDD)-immunoreactivity in the salt gland of the Pekin duck.

A novel peptide hormone, atrial natriuretic factor/cardiodilatin (ANP/CDD), was recently isolated and characterized from mammalian heart. Its presence has been demonstrated in several organs that contribute to water and sodium homeostasis, such as salivary glands. This study demonstrates the presence of ANP/CDD immunoreactivity in the salt gland of Pekin ducks by high performance liquid chromatography, radioimmunoassay and immunocytochemistry, using a specific antibody against atriopeptide I. A small number of distinct, ovoid or cuboid shaped ANP/CDD-immunoreactive cells were localized in the connective tissue surrounding and separating the central secretory tubules, whereas no immunostaining was observed in the peripheral tubules. Salt glands of ducks that were adapted to salt water revealed a significant hypertrophy of their secretory lobules. However, no differences were found between the number or localization of immunoreactive cells in the salt gland of salt water-acclimatized ducks and nonstimulated glands of ducks that were housed with ad libitum access to fresh water. Our results indicate that ANP/CDD may play a role in the regulation of sodium secretion in the salt gland of aquatic birds.

Animals↗
PubMed1989

Ventilatory, circulatory, endocrine, and renal effects of almitrine infusion in man: a contribution to high altitude physiology.

Diuresis at altitude was thought to be the result of chemoreceptor stimulation leading to a reduction of cardiac volume overload. This hypothesis was tested in ten young, healthy subjects by infusion of almitrine (0.5 mg.kg-1 body mass within 30 min) assuming analogous sites of action, i.e. arterial chemoreceptors and pulmonary vessels, for almitrine as for hypoxic hypoxia. The results show that almitrine increases ventilation, heart rate, systolic blood pressure, central venous pressure and natriuresis, but fails to increase significantly atrial natriuretic peptide plasma concentration and diuresis. It is concluded: (1) that almitrine has similar sites of action as hypoxic hypoxia at about 5000 m, (2) that natriuresis during arterial chemoreceptor stimulation might reduce cardiac volume overload, (3) that the volume excretion hypothesis, in particular the pathways from the cardiac volume overload to the water diuresis, need, for an understanding of the hypoxia-induced diuresis, further direct investigations at altitude.

Adult↗
PubMed1989

Converting enzyme inhibitors and their effects on the renin-angiotensin system of the blood vessel wall.

A local vascular tissue renin-angiotensin system (RAS) may contribute to blood pressure control and the maintenance of high blood pressure in some forms of hypertension, independently of the plasma RAS. Vascular converting enzyme (CE), present mainly in the endothelial layer of arteries and veins, can be altered in hypertension. Locally generated vascular angiotensin II (ANG II) may exert a number of actions on vascular tone and function, including directly and sympathetically mediated vasoconstriction, changes in vascular compliance in larger vessels, influence on vascular reactions to inflammation and injury, and alterations in vascular texture. Orally administered CE inhibitors have been shown to block not only the plasma RAS but also CE in the vasculature, leading to decreased vascular ANG II concentrations and possibly to an accumulation of locally generated vasodilator peptides and prostaglandins in the vascular wall. In spontaneously hypertensive rats, the slow recovery of CE activity in the vasculature on drug withdrawal was more closely associated with the slow return of blood pressure to hypertensive levels than the fast recovery of the plasma RAS. These and other experimental data discussed in this article favor the hypothesis that local CE inhibition in the vascular wall of resistance vessels, large arteries and veins contributes to the beneficial therapeutic effects of CE inhibitors in cardiovascular disorders such as hypertension and congestive heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Dilatation of the right atrium stimulates phosphatidylinositol turnover.

1. Dilatation of the rat right atria caused a stimulation of the phosphatidylinositol turnover pathway as measured by an increase in the accumulation of inositol phosphates in isolated, perfused hearts. 2. In right atria, increases were detected after 1 min dilatation and maximal increases were observed after 10 min. Dilatation for 10 min caused an increase in inositol monophosphate inositol bisphosphate and inositol trisphosphate from 23.3 +/- 0.9, 15.4 +/- 0.4, and 9.5 +/- 0.3 (mean and s.e.m., n = 7 ct/min per mg tissue) to 74.6 +/- 2.3, 20.2 +/- 1.3 and 13.6 +/- 1.5 (n = 8), respectively (P less than 0.01 for all inositol phosphates.) 3. These results show that the myocardium can respond to dilatation by an activation of the phosphatidylinositol turnover pathway.

Animals↗
PubMed1989

Atrial natriuretic peptide in a rat model of cardiac failure. Atrial and ventricular mRNA, atrial content, plasma levels, and effect of volume loading.

This study examined the relation between synthesis, atrial storage, and plasma levels of atrial natriuretic peptide (ANP), and it examined plasma ANP levels and hemodynamic output in response to volume expansion in a rat model of myocardial infarction and failure. Arterial ANP concentrations did not correlate linearly with infarct size, but they did show an abrupt increase when infarct size exceeded 30% of the left ventricle, similar to the abrupt increase of left ventricular end-diastolic pressure with infarct size greater than 30%. Consequently, a close relation was found between plasma ANP levels and left ventricular end-diastolic pressure (n = 23, r = 0.89, p less than 0.001). Atrial ANP content per gram of tissue but not ANP content per pair of atria was reduced in rats with large infarcts (greater than 40%, p less than 0.05 vs. control animals). ANP mRNA level per pair of atria (related to total atrial RNA), determined by liquid hybridization (controlled by northern blot analysis), was increased by 38% in infarcted rats (p less than 0.05 vs. controls), but the ratio of atrial ANP mRNA relative to atrial beta-actin mRNA levels was not increased. Right and left ventricular ANP mRNA level increased by 90% and 380%, respectively, far exceeding the concomitant increase in beta-actin mRNA (+26% in the left ventricle). Plasma ANP increased with volume loading in controls and rats with moderate infarcts but not in rats with large infarcts despite a similar increase in right atrial pressure (compared with control animals); thus, the relation of delta ANP/delta right atrial pressure exerted by volume loading decreased in rats with large infarcts. Similarly, the response of cardiac output and renal blood flow (determined by radioactive microspheres) to volume loading was attenuated in rats with large infarcts. Thus, in this model of chronic cardiac failure, the activation of the ANP system is closely coupled with the increase in intracardiac pressures without correlating linearly to the extent of myocardial loss. Second, in severe cardiac failure, additional stimulation such as volume loading may elicit only an attenuated ANP secretion response, for example, due to saturation of the ANP receptor sensing system or to a limited transformation rate of pro-ANP. Third, the increase in atrial ANP synthesis and the increase in atrial ANP gene expression seems limited; however, substantial specific ANP gene expression occurs in the ventricles, which, in turn, may contribute to increased plasma ANP levels in chronic heart failure.

Animals↗
PubMed1989

Myocardial stretch stimulates phosphatidylinositol turnover.

The mammalian myocardium responds to stretch by increasing both contractility and the release of atrial natriuretic peptide. These effects are observed in isolated perfused heart preparations as well as in vivo. That atrial natriuretic peptide release can be stimulated by activation of the phosphatidylinositol turnover pathway suggests a possible mechanism by which stretch might activate a biological response. Accordingly, experiments were performed to examine the effect of dilatation of the right atrium on the phosphatidylinositol turnover pathway measured in isolated perfused hearts. Dilatation of the right atrium caused a stimulation of the phosphatidylinositol turnover pathway as measured by an increase in the accumulation of inositol phosphates. In right atria, increases were detected after 1 minute of dilatation, and maximal increases were observed after 10 minutes. Dilatation for 10 minutes caused an increase in inositol monophosphate, inositol bisphosphate, and inositol trisphosphate from 23.3 +/- 0.9, 15.4 +/- 0.4, and 9.5 +/- 0.3 cpm/mg tissue (mean +/- SEM, n = 7) to 74.6 +/- 2.3, 20.2 +/- 1.3, and 13.6 +/- 1.5 cpm/mg tissue (n = 8), respectively (p less than 0.01 for all inositol phosphates). Smaller increases were observed in the other chambers of the hearts. Perfusion with propranolol, prazosin, and atropine (all 1 microM) did not alter the inositol phosphate response to dilatation, indicating that it was not secondary to release of norepinephrine or acetylcholine. Dilatation of the right ventricle also caused a stimulation of inositol phosphate accumulation, but this was lower than after dilatation of the right atrium. These results show that the myocardium can respond to dilatation by an activation of the phosphatidylinositol turnover pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Endothelin has potent inotropic effects in rat atria.

Endothelin, a novel peptide recently isolated from aortic endothelial cells, is one of the most active vasoconstrictors yet characterized. We report that endothelin is also a very potent inotropic substance, as demonstrated in isolated rat heart atria. The effects were observed at nanomolar concentrations and appeared to be due to a direct action of the peptide on the heart muscle cells. Thus, endothelin is not only a powerful vasoconstrictor but also has potent contractile effects on cardiac myocytes.

Animals↗
PubMed1988

Role of right and left atrial dimensions for release of atrial natriuretic peptide in left-sided valvular heart disease and idiopathic dilated cardiomyopathy.

To evaluate the role of atrial dimensions for release of atrial natriuretic peptide (ANP), right and left atrial dimensions (cross-sections) were determined by 2-dimensional echocardiography in 50 patients with left-sided valvular heart disease or idiopathic dilated cardiomyopathy. All patients underwent right- and left-sided heart catheterization with measurement of central hemodynamics. Plasma samples for ANP were withdrawn from femoral vein (ANPv) and ascending aorta. An estimate of right and left meridional atrial wall stress was derived by multiplying cross-sectional areas with pressures of the respective atria. As expected ANPv was closely related to mean right (r = 0.63; p less than 0.001; n = 50) and left atrial pressures (r = 0.61; p less than 0.001; n = 47). Furthermore, a positive correlation between ANPv and right (r = 0.56; p less than 0.001; n = 48) and left (r = 0.30; p less than 0.05; n = 48) atrial cross-sections was obtained. Finally, an excellent relation was found between ANPv and right (r = 0.73; p less than 0.001; n = 48) as well as left (r = 0.58; p less than 0.001; n = 44) meridional atrial wall stress, indicating that atrial wall stress rather than atrial pressures or dimensions alone determines plasma ANP concentrations. However, for identical right and left meridional atrial wall stress 3- to 4-times higher plasma ANPv levels were obtained in patients with idiopathic dilated cardiomyopathy than in patients with left-sided valvular heart disease. This indicates that release of ANP to the same stimulus may be modulated by the nature of the underlying heart disease.

Adult↗
PubMed1988

Endogenous tissue renin-angiotensin systems. From molecular biology to therapy.

Expression of the genes for renin and angiotensinogen has been documented in the heart and brain of several species, including rodents and primates. In the same tissues, local generation of angiotensin II has also been demonstrated. Neuropeptidergic brain angiotensin and local cardiac angiotensin participate in cardiovascular regulation. Inhibition of cardiac angiotensin II protects against deleterious arrythmogenic and metabolic effects of transient regional myocardial ischemia, and blockade of brain angiotensin II effectively lowers blood pressure in spontaneously hypertensive rats. It is surmised therefore that the therapeutic effects of converting enzyme inhibitors are, in part, brought about by inhibition of local tissue angiotensin II generation in addition to their interference with the hormonal plasma renin-angiotensin system. This would help to explain their therapeutic efficacy in pathophysiologic conditions in which hypertension is associated with low plasma renin activity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

In situ hybridization demonstrates vasopressin gene transcription in hypothalamic neurons of crossbred hypertensive x diabetes insipidus rats.

In situ hybridization, Northern blotting, and solution hybridization assay were used to examine vasopressin-gene messenger ribonucleic acid (mRNA) transcripts in hypothalamic tissue from five strains of rats: Long-Evans, Wistar-Kyoto, and diabetes insipidus (Brattleboro) rats, spontaneously hypertensive-stroke-prone rats, and cross-bred diabetes insipidus x spontaneously hypertensive-stroke-prone rats. A 290 base-pair, single-stranded RNA probe, with 221 bases complementary to exon C of the vasopressin gene was synthesized by the SP6 transcription vector system. This probe labeled appropriate neurohypophysial hypothalamic neurons, as well as suprachiasmatic nucleus cells, in tissue samples from all five strains of rats. Confirming other recent hybridization results with diabetes insipidus rat brain tissue, diabetic animals were found to transcribe their mutated vasopressin gene. In addition, this investigation found that the cross-bred diabetic-hypertensive rat also synthesizes a vasopressin-gene messenger ribonucleic acid transcript. Quantitative analyses of solution and in situ hybridization results suggested the cross-bred diabetic-hypertensive rat exhibits a level of vasopressin-gene messenger ribonucleic acid similar to diabetes insipidus rats. This observation is consistent with previous data on the cross-bred diabetic-hypertensive rat which suggests they inherit the mutant vasopressin gene from Brattleboro rats.

Animals↗
PubMed1988

Effect of sodium chloride and sodium bicarbonate on blood pressure in stroke-prone spontaneously hypertensive rats.

1. To test the hypothesis that NaCl increases blood pressure, while NaHCO3 does not, we measured the effect of an NaHCO3-containing mineral water on blood pressure in stroke-prone spontaneously hypertensive (SHR-SP) and Wistar-Kyoto (WKY) rats. We compared mineral water with equimolar amounts of NaCl and demineralized drinking water in six groups of 20 rats each over 24 weeks. 2. NaCl consistently increased blood pressure in both SHR-SP and WKY compared with demineralized water, while mineral water did not. 3. We studied the possible role of sodium-regulating hormones. Sodium, potassium-dependent adenosine triphosphatase activity was decreased by NaCl and by age, but not by mineral water. The concentration of atrial natriuretic peptide was greater in SHR-SP, but was not influenced by the two regimens. Components of the renin-angiotensin-aldosterone system and 18-hydroxydeoxycorticosterone tended to decrease with NaCl, but not with mineral water. 4. Plasma pH values in the six groups of rats were not different; however, SHR-SP had consistently lower PCO2 and HCO3- values and higher anion gap values than WKY rats. These values were not influence by the two regimens. 5. NaCl elevates blood pressure in SHR-SP while NaHCO3 does not. The changes in hormones regulating sodium homoeostasis suggest that NaCl induces volume expansion while NaHCO3 does not. The effect may be related to influences on renal sodium reabsorption by chloride and bicarbonate. The possible role of increased proton excretory activity in SHR-SP remains to be determined.

Animals↗
PubMed1988

Quantification of renin mRNA in various mouse tissues by a novel solution hybridization assay.

A new solution hybridization assay was established for the measurement of renin mRNA. The assay makes use of a radioactively labelled renin complementary RNA as hybridization probe and allows rapid and sensitive detection of renin mRNA in amounts as low as 0.5 pg. With this assay it was possible to quantify renin mRNA in tissues with low-gene expression such as brain and heart as well as in testis, kidney and the submandibular gland (SMG) of mice. The concentrations in these organs were 0.03, 0.07, 1, 5.2 and 164 pg renin mRNA/micrograms RNA, respectively. These results are in agreement with Northern blotting experiments. The general applicability and ease of the solution hybridization assay described here should greatly improve the rapidity of mRNA measurements in future functional studies.

Animals↗
PubMed1988

Receptor autoradiographical evidence of a preferential reduction of binding sites for atrial natriuretic factor in renal papilla of the spontaneously hypertensive rat.

In the spontaneously hypertensive rat (SHR) as well as in the pathophysiological states with volume retention, high levels of atrial natriuretic factor (ANF) do not produce adequate diuresis and natriuresis. We have investigated the question whether the reduced effectiveness of ANF could be due to a reduction of the ANF binding. Evidence is provided by quantitative autoradiography with [125I]ANF than higher ANF plasma levels in SHRSP compared to normotensive WKY rats are associated with a reduced number of binding sites (25%) in the renal papilla as well as in the subfornical organ (69%). This could contribute to the reduced response of ANF in SHRSP.

Animals↗
PubMed1988

Substance P induces a cardiovascular defense reaction in the rat: pharmacological characterization.

In this study in conscious rats, we tested the hypothesis that substance P, a central pressor peptide and a potential transmitter substance of pain pathways, could be involved in the cardiovascular defense reaction that is typically associated with unpleasant sensory stimuli. The hemodynamic responses to centrally administered substance P were pharmacologically characterized. The increases in blood pressure and heart rate after intracerebroventricular injections of substance P were accompanied by mesenteric and renal vasoconstriction and hind limb vasodilation (pulsed-Doppler flow probes). The pressor and vasoconstrictor responses were attenuated by peripheral alpha 1-adrenoceptor blockade with prazosin but were not influenced by blockade of vascular vasopressin receptors with d(CH2)5Tyr(Me) arginine vasopressin (AVP). Cardiac beta 1-adrenoceptor blockade with metoprolol abolished the tachycardic and reduced the pressor responses. Substance P-induced hind limb vasodilation was not sensitive to intravenous atropine but was largely prevented by peripheral beta 2-adrenoceptor blockade with ICI 118,551. Thus, the substance P-induced pressor effects are mediated by alpha 1-adrenergic sympathetic vasoconstriction and beta 1-adrenergic cardiac stimulation, whereas the hind limb vasodilation is mainly due to beta 2-adrenergic stimulation. Substance P dose-dependently (0.01-10 micrograms i.c.v.) released oxytocin but not vasopressin or adrenocorticotropic hormone (ACTH) from the pituitary gland. High doses reduced basal ACTH levels. Together with the hemodynamic responses, a behavioral arousal reaction was observed, which included increased locomotion, grooming, scratching, and skin biting. Our results demonstrate that a neuropeptide can induce classic cardiovascular defense reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1988

Measurement of mRNA by solution hybridization with 32P-labelled single stranded cRNA probe ("SP6 test"). Comparison with a 32P-labelled single stranded cDNA as hybridization probe ("S1 test") for measurement of AVP mRNA.

Radioactively labelled cRNA for the rat AVP gene exon C was synthetized from a pSP64-vector and used for solution hybridization measurement of AVP mRNA ("SP6 test"). For comparison hybridization was carried out with a gel-purified radioactively labelled cDNA probe synthetized by primer extension of AVP gene exon C cloned into an M13mp9 phage vector DNA ("S1 test"). Both tests had a comparable sensitivity of up to 0.2 pg AVP mRNA. Under optimal hybridization conditions kinetics were similar in both tests. The fast and easy preparation of large amounts of labelled cRNA probe and simple determination of absolute amounts of mRNA by saturation kinetics without need of a mRNA standard makes the "SP6 test" an attractive alternative to the known "S1 test". The "SP6 test" should be applicable for a wide variety of genes.

Animals↗
PubMed1988

Vasopressin gene expression in hypertensive, normotensive, and diabetes insipidus rats.

This investigation examined the presence and abundance of vasopressin-gene messenger ribonucleic acid (mRNA) transcripts in hypothalamic tissue from five strains of rats: Long Evans, Wistar-Kyoto, and diabetes insipidus (Brattleboro) rats, stroke-prone spontaneously hypertensive rats, and cross-bred diabetes insipidus x stroke-prone spontaneously hypertensive rats. A single-stranded RNA probe complementary to exon C of the vasopressin gene was utilized for in situ hybridization and identified hypothalamic 'vasopressinergic' neurons in tissue from all five strains of rats. The results obtained by solution and in situ hybridization suggested the cross-bred diabetic-hypertensive rat exhibits a level of vasopressin-gene messenger ribonucleic acid similar to diabetes insipidus rats. This observation is consistent with previous physiological data which suggests cross-bred diabetic-hypertensive rats inherit the mutated vasopressin gene of the Brattleboro rat.

Animals↗
PubMed1988

Brain angiotensin: pathways and pharmacology.

The existence of a brain renin-angiotensin system (RAS) as one of various tissue RASs is now firmly established. Angiotensin-containing pathways within brain areas involved in central blood pressure regulation have been described. Evidence from biochemical, neurophysiologic, pharmacologic, and most recently, molecular genetic studies indicate that the brain RAS is regulated independently of the hormonal RAS and may contribute to blood pressure control and body fluid homeostasis. In addition, circulating angiotensin II can exert some of its action through stimulation of brain angiotensin receptors accessible from the blood. In experimental animal preparations of hypertension, especially in spontaneously hypertensive rats, an overactive brain RAS may be one of the factors involved in pathogenesis and maintenance of hypertension. In spontaneously hypertensive rats, inhibitors of the angiotensin II-generating converting enzyme (CE) have been shown to lower blood pressure by a central action when applied to the brain and to inhibit brain CE when applied systemically. The pathogenetic mechanisms underlying a particular cardiovascular disease and the characteristics of the CE inhibitor used (e.g., its lipid solubility governing penetration into tissue) may determine the degree to which CE inhibition within a given organ, such as the brain, contributes to the action of these drugs.

Angiotensin II↗