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Biomedical subjects

D Ganten

Publications and source records attributed to D Ganten.

At least 361 records · Page 20Linked to original sources
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

Dual peroxidase and colloidal gold-labeling study of angiotensin converting enzyme and angiotensin-like immunoreactivity in the rat subfornical organ.

The cellular relationships between angiotensin converting enzyme (ACE) (EC 3.4.14.1) and angiotensin-like immunoreactivity (AGLI) were examined in the subfornical organ (SFO). Brains from adult rats were fixed by vascular perfusion with 3.75% acrolein and 2% paraformaldehyde. The region containing the SFO was then sectioned on a vibrating microtome. Partially permeabilized sections were immunocytochemically labeled using the peroxidase-antiperoxidase (PAP) or combined PAP and immunogold methods. Goat antiserum to ACE was localized to both non-neuronal and neuronal cells within the SFO. Intense peroxidase immunoreactivity for ACE was associated with the ventricular and basal surface of ependymal cells, the luminal surface of the vascular endothelium, portions of glial membranes exposed to extracellular spaces, and membranous organelles within neuronal processes. Two antisera raised in rabbits against angiotensin II showed peroxidase immunoreactivity within the extracellular spaces and throughout the cytoplasm of numerous axon terminals and a few perikarya and dendrites in the SFO. Axon terminals and dendrites also showed aggregates of AGLI in smooth membranes and vesicles near the plasmalemma. Gold labeling for AGLI was evident in only 6% of the axon terminals and in a smaller number of dendrites containing peroxidase immunoreactivity for ACE. The low incidence of terminals containing both markers appeared to at least partially reflect limited penetration of the 10 nm gold particles. These results provide the first ultrastructural evidence that ACE is associated with the plasmalemma and membranous organelles strategically located for interaction with precursors of angiotensin II or other peptides within the cerebrospinal fluid, extracellular spaces and neurons of the SFO.

Angiotensin I↗
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

[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

Electrolyte intake and blood pressure: a study in contradictions and controversy.

The widely accepted recommendation that hypertensive subjects benefit from a reduction of sodium intake has lately been challenged by a number of publications. From one analysis of the First National Health and Nutrition Examination Survey (NHANES) in the USA, the conclusion was reached that hypertension was associated more frequently with low nutritional sodium intake and low calcium intake. Other authors analysing the same data but using different criteria and statistical methods did not confirm such conclusions. The criticisms of epidemiological data concerning the relationship between salt intake and hypertension include frequently inconsistent definition of hypertension, failure to consider methodological uncertainties in the measurement of salt intake and excretion and inadequate control of confounding variables such as age, race, sex, body mass index and lifestyle. The claimed link between nutritional calcium and blood pressure is completely unclear and needs careful investigation. A reduction of sodium intake from the present day excessive amounts to moderate intakes of 3-6 g per day is still recommended in order to prevent the establishment of high blood pressure, to reduce hypertensive blood pressure levels or to reduce the doses of antihypertensive drugs. With mild hypertension being the main problem of high blood pressure management, further research is necessary to place dietary intervention in the non-pharmacological treatment of hypertension on a firmer, more rational footing.

Blood Pressure↗
PubMed1985

Effects of converting enzyme inhibitors: ramipril and enalapril on peptide action and sympathetic neurotransmission in the isolated heart.

The role of converting enzyme (CE) in heart function was studied by assessing the inhibition of CE activity in rat heart tissue and in isolated perfused hearts from rat, guinea-pig and rabbit (Langendorff technique). Angiotensin I (ANG I) added to the perfusate reduced coronary flow (FLO) in all species, increased force of contraction (CON) in rats, decreased CON in guinea-pigs and had no effect on CON in rabbits. In contrast, bradykinin (BK) increased FLO in all species, decreased CON in rats, increased CON in guinea-pigs and had no effect on CON in rabbits. The CE inhibitors ramipril (HOE498) 1 mg/kg and enalapril (MK421) 30 mg/kg given orally 1 h prior to killing of the animals inhibited the ANG I effects and potentiated the BK effects but had no effects on the action of ANG II. The same doses of the two CE inhibitors produced up to 24 h inhibition of CE activity measured biochemically in the heart after single oral doses. Electrical sympathetic stimulation of the cardiac nerves (SNS) in isolated rabbit heart resulted in an increase of HR and CON and in an initial decrease and subsequent increase of FLO. The effects of SNS on HR and FLO were significantly reduced following HOE498 (1 mg/kg) pretreatment. The results suggest that local CE is involved in the regulation of peptide effects in the heart, including the ANG II-mediated facilitation of neurotransmission.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

The distribution of angiotensin II-immunoreactive cells and fibers in the paraventriculo-hypophysial system of the rat.

Angiotensin II (AII)-immunoreactive cell bodies were found in all parts of the paraventricular nucleus of the hypothalamus (PVH) in the normal, colchicine-treated rat. The greatest concentration of cells was found in the posterior part of the magnocellular division of the nucleus, while scattered cells were found in all 5 parts of the parvocellular division. In comparison, the Brattleboro rat showed similar cell staining in parvocellular parts of the PVH, although a substantial decrease in the number of AII-stained cells was found in the magnocellular division. In the normal animal, fiber staining was evident in both laminae of the median eminence. This immunostaining was selectively enhanced in the internal lamina following water deprivation, and was selectively enhanced in the external lamina following adrenalectomy. The Brattleboro rat was similar to the normal animal with regard to staining of the external lamina, but, consistent with the diminished number of immunoreactive magnocellular neurons, little immunostaining in the internal lamina was detected. Unilateral lesions of the PVH selectively diminished staining of fibers and varicosities in the ipsilateral external lamina, while bilateral lesions virtually eliminated staining on both sides. The findings in the Brattleboro rat indicate that specific subpopulations of both parvocellular and magnocellular neurons in the PVH contain an antigen that is immunologically similar to synthetic AII and unrelated to vasopressin or its prohormone.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1985

The cardiovascular effects of oxytocin in conscious male rats.

In conscious, chronically instrumented normotensive male Wistar rats intravenous (i.v.) administration of oxytocin (OXT) (greater than or equal to 100 ng) induced a dose-related biphasic change in mean arterial pressure (MAP). This consisted of an initial pressor effect accompanied by bradycardia and a decrease in cardiac output (CO), followed by a more prolonged fall in MAP which reached a maximum 30 min after injection and was accompanied by an increase in CO. The more specific (Thr4,Gly7]OXT analogue (0.01-10 micrograms i.v.) caused a dose-related fall in MAP and a rise in CO which reached a maximum after 15-30 min. Similarly in spontaneously hypertensive rats of the stroke prone strain (SHRSP) an initial pressor effect and delayed fall in MAP were apparent after OXT (0.1 and 10 micrograms i.v.) only the decrease in MAP being evident with the [Thr4,Gly7]OXT analogue. These responses were significantly larger than those observed in Wistar Kyoto controls. The pressor effects are therefore interpreted to be due to vasopressin receptor activation while the depressor effects appear to be oxytocin specific. In sinoaortic denervated rats, OXT (0.1 and 10 micrograms i.v.) induced an enhanced initial pressor effect with a much reduced reflex bradycardia and fall in CO. A larger and more prolonged delayed fall in MAP was apparent with both OXT and [Thr4,Gly7]OXT accompanied by a decrease in CO when compared to sham-operated controls. Intracisternally (i.c.) administered OXT (0.05-10 ng) had no effect on MAP or heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Localization of renin (EC 3.4.23) and converting enzyme (EC 3.4.15.1) in nerve endings of rat brain.

Synaptosomes and lysosomes of rat brain were separated by differential centrifugation and a two-step gradient centrifugation with colloidal silica-gel (Percoll). The organelles were identified by the measurement of established marker-enzymes and by electronmicroscopy. Renin activity, measured by radioimmunoassay for angiotensin I (ANG I), was localized in the synaptosomes and cathepsin D-activity was found in the lysosomal fraction. Converting-enzyme activity was present in the renin-containing synaptosomes. Part of the brain renin activity could be activated by pre-incubation with trypsin. Affinity chromatography of an organelle-enriched brain fraction was carried out using a caseinyl-sepharose column and resulted in the separation of renin from cathepsin D activity; the renin peak was inhibited by antibodies raised against rat kidney renin. We conclude, that the formation of ANG I and its activation to angiotensin II (ANG II) by converting enzyme is possible in synaptosomes. This adds further evidence to an intraneuronal synthesis of ANG I and ANG II in the brain and is in support of previous results demonstrating an intraneuronal localization of the components of the brain renin-angiotensin system.

Animals↗
PubMed1985

Altered neuropeptide concentrations in spontaneously hypertensive rats: cause or consequence?

Changes in brain neuropeptide content in spontaneously hypertensive rats may be primarily related to the development of hypertension or may be secondary consequences of it. We have measured brain concentrations of beta-endorphin, Leu-enkephalin, arginine vasopressin (AVP) and oxytocin (OXT) in stroke-prone spontaneously hypertensive rats (SHRSP) and in age-matched normotensive Wistar Kyoto (WKY) controls, as well as in SHRSP with normalized blood pressure by chronic treatment with clonidine. Opioid peptide contents were measured in 12-, 18- and 24-week-old rats. beta-Endorphin was measured in the neuro-intermediate and anterior lobes of the pituitary, the hypothalamus, mid-brain and brain stem; Leu-enkephalin in the neuro-intermediate lobe of the pituitary, hypothalamus, mid-brain, brain stem, as well as in the spinal cord and adrenal glands. AVP and OXT were measured in the neuro-intermediate lobe of the pituitary, hypothalamus, brain stem and spinal cord. beta-Endorphin in the neuro-intermediate lobe of the pituitary was significantly higher in 12- and 18-week-old SHRSP. Adrenal gland Leu-enkephalin was lower in SHRSP as compared with the WKY. OXT and AVP contents were markedly reduced in all brain regions of SHRSP except the neuro-intermediate lobe of the pituitary, where no significant changes were found. In no case did long-term antihypertensive treatment with clonidine reverse the altered peptide content in the SHRSP. We conclude that alterations in brain neuropeptide content in SHRSP are not secondary to hypertension. The blood pressure lowering activity of clonidine appears not to depend on major alterations of peptide concentrations. A genetic defect in the synthesis of adrenal enkephalins and hypothalamic OXT and AVP seems likely from these studies.

Animals↗
PubMed1985

Organization of angiotensin II immunoreactive cells and fibers in the rat central nervous system. An immunohistochemical study.

The distribution of angiotensin II (AII)-immunoreactive cells and fibers was examined in adult male Sprague-Dawley rats with and without colchicine pretreatment. As seems to be the case for a number of other neuropeptides, AII is preferentially found in brain stem, hypothalamic, and limbic structures involved in the control of homeostatic functions. AII-stained cell bodies were most prominent in magnocellular parts of the paraventricular and supraoptic nuclei, and cells were also found in parvocellular parts of the former. Other hypothalamic nuclei containing cell bodies include the suprachiasmatic nucleus, the medial preoptic area, and perifornical parts of the lateral hypothalamic area. Of considerable interest was robust staining in several of the circumventricular organs, in particular the subfornical organ, where both cells and fibers were found. The results of water deprivation and nephrectomy suggest that this staining does not represent uptake of circulating peptide, but instead, represents AII-containing neural connections. In the thalamus, AII-stained cells were found in the paraventricular nucleus, the central medial nucleus, the nucleus reuniens, and rostral parts of the zona incerta. Two cell groups in the basal telencephalon, in the dorsal part of the bed nucleus of the stria terminalis and in the medial nucleus of the amygdala, lay at either end of an AII-stained pathway coursing through the stria terminalis. In the midbrain, immunoreactive cells were found in the interpeduncular and peripeduncular nuclei, and one pontine cell group was detected in the most lateral part of the lateral parabrachial nucleus. The only AII-stained cells in the medulla were in the nucleus of the solitary tract, near the margin of the area postrema. Fibers were found at all levels of the central nervous system, from the olfactory bulbs to the spinal cord, where terminal fields were observed in the substantia gelatinosa and in the intermediolateral cell column. Longitudinally oriented fibers were present throughout the periventricular fiber system and in the medial forebrain bundle, including its caudal extension in ventrolateral parts of the brain stem. It is suggested that, at many different levels, AII serves as both a hormone and neurotransmitter for fluid balance.

Angiotensin II↗
PubMed1985

Differential effects of central angiotensin II and substance P on sympathetic nerve activity in conscious rats. Implications for cardiovascular adaptation to behavioral responses.

The centrally induced effects of angiotensin II and substance P on the cardiovascular system and on neuronal efferent activity of the splanchnic, renal, and adrenal nerves were investigated in chronically instrumented conscious rats. The pressor responses to substance P injected into the lateral brain ventricle were accompanied by marked and short latency increases in heart rate, cardiac output, splanchnic, renal, and adrenal nerve activity, and a rise in plasma noradrenaline and adrenaline. Behaviorally, an arousal-type reaction was observed. In contrast, the pressor responses to intracerebroventricular angiotensin II were associated with initial decreases in heart rate, cardiac output, splanchnic, renal, and adrenal nerve activity, and a fall in plasma noradrenaline at the time of the maximal blood pressure increase. In some but not all animals, a second blood pressure peak associated with increases in heart rate and splanchnic nerve activity was observed after several minutes. Incomplete chronic sinoaortic baroreceptor deafferentiation prevented the angiotensin II-induced fall in heart rate but not the initial fall in splanchnic nerve activity. The decreases in splanchnic nerve activity also occurred in diabetes insipidus rats and persisted in Long Evans rats after vascular vasopressin receptor blockade with d(CH2)5AVP, despite marked reductions of the pressor responses in both groups. Peripheral alpha-adrenoceptor blockade with prazosin or ganglion blockade with hexamethonium inhibited the central angiotensin II pressor responses only in combination with vasopressin receptor blockade. On the other hand, either sympatholytic drug, alone, abolished the pressor responses in the diabetes insipidus rats. This indicates that in intact conscious rats the central pressor effects of angiotensin II are initiated by vasopressin release but become dependent on the sympathetic nervous system when vasopressin is absent or not effective. When rats were allowed to drink in response to angiotensin II, a further sharp rise in blood pressure occurred, together with increases in heart rate and splanchnic nerve activity. The results demonstrate fundamental differences in the mechanisms by which central pressor peptides can influence cardiovascular and autonomic function. It is conceivable that the distinct sympathetic response patterns to central angiotensin II and substance P receptor stimulation form part of a specific cardiovascular adjustment to the individual behavioral reactions, such as drinking, as in the case of angiotensin II, or arousal within the central processing of pain, as in the case of substance P.

Action Potentials↗