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Biomedical subjects

M G Ziegler

Publications and source records attributed to M G Ziegler.

At least 109 records · Page 6Linked to original sources
PubMed1990

Sources of urinary catecholamines in renal denervated transplant recipients.

When a human kidney is transplanted, sympathetic nerves to that kidney are cut. We infused 3H-noradrenaline and then measured noradrenaline, dopamine and 3H-noradrenaline levels in the plasma and urine of renal transplant recipients and uninephrectomized control subjects. Less than 10% of 3H-noradrenaline cleared from the plasma appeared in the urine. Noradrenaline and dopamine appeared in the urine of transplant recipients at one-third the rate of control subjects, even though 3H-noradrenaline levels were slightly higher in the urine of transplant recipients. Transplant patients had a noradrenaline clearance of 128 +/- 50 ml/min, compatible with simple glomerular filtration, while controls had a higher calculated clearance of 229 +/- 41 ml/min. Plasma dopamine levels were very low compared with urinary dopamine. These results suggest that two-thirds of renal noradrenaline and dopamine depend on the presence of renal nerves. Almost all urinary dopamine comes from the kidney. For noradrenaline, urinary excretion is a very minor pathway for clearance from the plasma.

Adult↗
PubMed1990

Lung epinephrine synthesis.

We studied in vitro and in vivo epinephrine (E) synthesis by rat lung. Nine days after removal of the adrenal medullas, circulating E was reduced to 7% of levels found in sham-operated rats but 30% of lung E remained. Treatment of demedullated rats with 6 hydroxydopamine plus reserpine did not further reduce lung E. In the presence of S-[3H]adenosylmethionine lung homogenates readily N-methylated norepinephrine (NE) to form [3H]E. The rate of E synthesis by lung homogenates was progressively more rapid with increasing NE up to a concentration of 3 mM, above which it declined. The rate of E formation was optimal at an incubation pH of 8 and at temperatures of approximately 55 degrees C. We compared the E-forming enzyme(s) of lung homogenates with those of adrenal and cardiac ventricle. The adrenal contains mainly phenylethanolamine N-methyltransferase (PNMT), which is readily inhibited by SKF 29661 and methylates dopamine (DA) very poorly. Cardiac ventricles contain mainly nonspecific N-methyltransferase (NMT), which is poorly inhibited by SKF 29661 and readily methylates both DA and NE. Lung homogenates were inhibited by SKF 29661 about half as well as adrenal but more than ventricle. We used the rate of E formation from NE as an index of PNMT-like activity and deoxyepinephrine synthesis from DA as an index of NMT-like activity. PNMT and NMT activity in rat lung homogenates were not correlated with each other, displayed different responses to change in temperature, and were affected differently by glucocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1990

Pertussis toxin treatment of whole blood. A novel approach to assess G protein function in congestive heart failure.

This study was designed to assess G protein function in mononuclear leukocytes (MNL) of patients with congestive heart failure (CHF). MNL membranes were ADP-ribosylated in vitro in the presence of pertussis or cholera toxin. The amount of pertussis toxin substrates did not differ significantly between CHF patients (6,100 +/- 224 fmol/mg, n = 23) and age-matched healthy control subjects (5,812 +/- 972 fmol/mg protein, n = 19). Among the CHF patients, no differences were observed between those with idiopathic and ischemic CHF. The amount of cholera toxin substrates also did not differ significantly between CHF patients (7,522 +/- 1,405 fmol/mg protein, n = 11) and control subjects (5,654 +/- 707 fmol/mg protein, n = 14). Moreover, basal and isoproterenol- and prostaglandin E1-stimulated cyclic AMP (cAMP) accumulation in MNL was similar in control subjects and patients. To detect more subtle alterations of the cAMP-generating system, we incubated anticoagulated blood with 250-400 ng/ml pertussis toxin for 4 hours at 37 degrees C. This treatment completely ADP-ribosylated the MNL pertussis toxin substrates. Incubation with pertussis toxin did not change basal or prostaglandin E1-stimulated cAMP generation in MNL of control subjects, but it significantly enhanced stimulated generation (443 +/- 44 vs. 643 +/- 93 pmol/10(7) cells, p less than 0.025) in MNL of CHF patients. This enhancement was most pronounced in the most severely ill patients (New York Heart Association class IV) and correlated with plasma norepinephrine levels, another marker of CHF severity (r = 0.798, n = 11, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate Ribose↗
PubMed1990

Adrenergic control of circulating lymphocyte subpopulations. Effects of congestive heart failure, dynamic exercise, and terbutaline treatment.

The current studies were undertaken to explore the relationship between enhanced sympathetic nervous activity and lymphocyte subset distribution in three settings: congestive heart failure, dynamic exercise, and beta-adrenergic agonist treatment. We compared the number and subset distribution of circulating lymphocytes in 36 patients with congestive heart failure and 31 age-matched control subjects. The number of circulating lymphocytes was lower in heart failure than in control. This was due to a reduction in Tsuppressor/cytotoxic and natural killer cells without significant alteration of Thelper cells. The extent of the alteration was similar in patients with idiopathic and ischemic heart failure, but the reduction was more pronounced in patients with New York Heart Association class III-IV than in class I-II. The plasma catecholamine elevation in heart failure was also independent of etiology but more pronounced in the more severely ill patients. We also assessed lymphocyte subsets after acute stimulation of sympathetic activity by dynamic exercise and after treatment with the beta-adrenergic agonist terbutaline. Dynamic exercise until exhaustion increased the number of circulating lymphocytes in healthy controls and heart failure patients in a subset-selective manner. By contrast, a 7-d treatment with terbutaline caused a reduction in the circulating number of lymphocytes in some subsets that was identical to that seen in heart failure patients. We conclude that prolonged sympathetic activity reduces the number of circulating lymphocytes by a beta-adrenergic mechanism. Such alterations might be involved in the pathophysiology of heart failure and other disease states involving increased activity of the sympathetic nervous system.

Adult↗
PubMed1990

Epinephrine synthesis in the rat iris.

Epinephrine (E) alters blood flow, intraocular pressure and pupillary constriction. The rat iris contained E-forming activity that was moderately specific for a phenylethanolamine and was inhibited by the phenylethanolamine-N-methyltransferase (PNMT) inhibitor SKF 29661. Unilateral superior cervical ganglionectomy decreased iris norepinephrine (NE) 63%, but failed to lower PNMT activity or E in the iris. Removal of both adrenal medullae markedly lowered circulating E levels, but had no effect on iris E. Further treatment with 6-hydroxydopamine and reserpine greatly lowered iris NE levels, but failed to decrease either iris E or E forming activity. The rat iris has non-neuronal E-forming enzymes which appear to synthesize most of the E contained in the iris.

Adrenal Glands↗
PubMed1989

Extraadrenal adrenaline formation by two separate enzymes.

Adrenaline (A) is synthesized in the adrenal medullae by the enzyme phenylethanolamine-N-methyltransferase (PNMT). After surgical removal of the adrenal medullae tissue A levels ranged from 22% of control in the heart to 125% of control in the liver. Use of a novel assay to measure tissue A formation revealed that many tissues can synthesize A using PNMT and another enzyme that N-methylates both noradrenaline and dopamine. These enzymes are non-neuronal, inducible and synthesize a major fraction of tissue and urine A.

Adrenal Medulla↗
PubMed1989

Short-term delay in blood processing does not alter basal or isoproterenol-stimulated cyclic AMP accumulation in human lymphocytes.

Isoproterenol-stimulated cyclic AMP (cAMP) accumulation in lymphocytes is an index of beta-adrenergic receptor functioning. It is not known if a delay between blood collection and subsequent cell preparation influences cAMP accumulation. We compared cAMP levels in lymphocytes processed from whole blood immediately after collection and following a 3.5 hour delay. There were no significant changes in either basal or stimulated levels of cAMP. This information may alleviate time constraints in certain experimental designs where immediate isolation of lymphocytes from whole blood may not be practical.

Adult↗
PubMed1989

Regulation of cardiac beta-adrenergic receptors by captopril. Implications for congestive heart failure.

The interaction of the renin-angiotensin system and the sympathetic nervous system in patients with congestive heart failure is not well understood. We tested the hypothesis that angiotensin-converting enzyme inhibitors can resensitize the beta-adrenergic receptor system. Guinea pigs were given captopril, isoproterenol, or both for 2 weeks. At death, cardiac sarcolemmal and light vesicle fractions and intact mononuclear leukocytes were prepared. Captopril treatment led to an up-regulation of cardiac beta 1- but not mononuclear leukocyte beta 2-adrenergic receptors and an increase in isoproterenol-stimulated adenylate cyclase activity in the heart. Animals treated with isoproterenol developed cardiac hypertrophy, had increased plasma norepinephrine levels, and had a decreased number and responsiveness of both cardiac and mononuclear leukocyte beta-adrenergic receptors. Concomitant treatment with captopril attenuated alterations of heart weight, plasma norepinephrine levels, and cardiac beta-receptor density and function. In contrast to its cardiac effects, captopril treatment did not diminish the down-regulation of mononuclear leukocyte beta 2-adrenergic receptors by isoproterenol. Our data suggest that captopril may resensitize the cardiac but not the mononuclear leukocyte beta-adrenergic receptor-adenylate cyclase system after long-term catecholamine exposure.

Adenylyl Cyclases↗
PubMed1989

Rat renal epinephrine synthesis.

Rats that underwent adrenal demedullation had a 93% decrease in plasma epinephrine (E) levels, but did not decrease their renal E. Even further treatment with 6-hydroxydopamine and reserpine failed to lower renal E levels. Similarly, urine E levels failed to decrease after adrenal demedullation and renal denervation. There is a renal E-synthesizing enzyme that differs from adrenal phenylethanolamine-N-methyltransferase (PNMT) in that it is only weakly inhibited by SKF 29661 and can synthesize epinine from dopamine, while adrenal PNMT does so poorly. When an adrenalectomized rat received intravenous [3H]methionine, its urine contained radioactivity that appeared to be [3H]E, with small amounts of [3H]epinine. However, after [3H]methionine was infused in the renal artery, the major product in urine appeared to be [3H]epinine, with a small amount of [3H]E. Adrenal demedullation induced renal E synthesis, but denervation returned the rate of renal E synthesis to control values. The combination of adrenal demedullation, 6-hydroxydopamine, and reserpine treatments increased renal E-forming activity to 350% of control. We conclude that appreciable portions of renal and urinary E are synthesized in the kidney by an enzyme distinct from PNMT. The enzyme is induced by some treatments that lower E and NE levels.

Adrenal Glands↗
PubMed1989

Catecholamines: study of interspecies variation.

In the last three decades, numerous articles on plasma catecholamine concentrations in various settings have been published in the medical literature. Despite this abundance of information, no summary article has analyzed the species variations in circulating catecholamine concentrations. In this paper, the plasma catecholamine responses to various stresses in 31 animal groups have been compiled from greater than 200 publications (with greater than 5000 animal subjects). Primitive cartilaginous fish such as the shark and the lamprey have the highest reported basal plasma catecholamine concentrations. Birds, mammals, and teleost fish have the lowest concentrations. The lower circulating catecholamine concentrations parallel anatomical changes in the development of the adrenal medulla and the development of the nervous system. Decapitation, hypoxia, hemorrhage, and hypothermia are the experimental conditions associated with the greatest stress-induced changes in plasma catecholamine concentrations. The differences in experimental design are tabulated to afford the reader an opportunity to compare catecholamine levels among species. The table provides a detailed guide to normal concentrations and normal responses in 31 species. This report gives a dynamic overview of catecholamine concentrations in human and animal physiology and may be particularly helpful to investigators involved in catecholamine research.

Animals↗
PubMed1988

A sensitive radioenzymatic assay for epinephrine forming enzymes.

Epinephrine (E) is formed in the adrenal medulla by phenylethanolamine-N-methyltransferase (PNMT), and in other tissues. Enzymes other than PNMT may be able to synthesize E, but this has been difficult to investigate because most assays do not have E as their final product. This assay produces 3H-E from norepinephrine (NE) and 3H-S-adenosylmethionine. The 3H-E is isolated on alumina, 3H-S-adenosylmethionine is precipitated and the 3H-E is suspended in diethylhexyl phosphoric acid in toluene for scintillation counting. The assay is sensitive and linear over a wide range. E was formed by most tissues tested. Brain and adrenal contained an enzyme specific for NE, but cardiac ventricle contained an enzyme that methylated both NE and dopamine. Denervated tissues in adrenal medullectomized rats contained very little NE, but still had E and E forming enzyme present. This assay detects a non-neuronal E forming enzyme with activity in vitro and in vivo.

Adrenal Medulla↗
PubMed1988

Atrial natriuretic factor in renal failure and posthemodialytic postural hypotension.

Atrial natriuretic factor (ANF) levels were ten times normal in hemodialysis patients before dialysis. ANF was not cleared by the dialyzer membrane but plasma levels decreased 47% by the end of dialysis. Patients undergoing peritoneal dialysis had plasma ANF levels four times normal and had detectable ANF in their dialysate. Hemodialysis patients with a marked fall in BP after dialysis had higher ANF levels (P less than 0.05) and lower norepinephrine (NE) levels (P less than 0.05) associated with a failure to increase NE in response to dialysis. Elevated ANF levels are associated with postdialysis hypotension in hemodialysis patients.

Adult↗
PubMed1988

Dose response to hydrochlorothiazide in hypertensives receiving a calcium channel blocker.

Seven hypertensive patients receiving the dihydropyridine calcium channel blocking agent nicardipine were given placebo, 6.25, 12.5, 25 and 50 mg hydrochlorothiazide (HCTZ) in a randomized crossover design. Blood pressure (BP) decreased by about 7/3 mmHg irregardless of dose. In contrast, potassium, glucose and uric acid increased in a dose-dependent fashion. The hypokalemic and hyperglycemic responses at 50 mg were larger than usually seen with HCTZ. Low doses of HCTZ provided a modest antihypertensive effect, but 25 and 50 mg of HCTZ were no more effective in lowering BP and gave unusually large metabolic side effects when combined with a calcium channel blocker.

Blood Glucose↗
PubMed1988

Cough caused by cilazapril.

Angiotensin-converting enzyme (ACE) inhibitors are a group of drugs recently introduced to treat hypertension and congestive heart failure. There are many reports of a dry cough in patients treated with (ACE) inhibitors, but this is often considered a rare side effect. Eleven of 30 patients treated with the investigational ACE inhibitor cilazapril complained about a chronic cough.

Adult↗
PubMed1988

The effect of hemorrhage and resuscitation on serum levels of immunoreactive atrial natriuretic factor.

To determine if atrial natriuretic factor (ANF) might have a role in blood volume regulation during hypovolemia, the serum level was measured before and after hemorrhage and resuscitation (RESUS) in a porcine shock model. Hemorrhage of 40% of the blood volume produced significant (p less than 0.01) decreases in mean arterial pressure, central venous pressure, and cardiac output and a significant increase in heart rate (HR), plasma renin activity, and catecholamines (p less than 0.01). Hemorrhage was also associated with a significant increase in ANF (p less than 0.05). All parameters except HR returned to baseline values with RESUS. The rise in ANF associated with moderate hemorrhage was unexpected, but may have been due to the profound tachycardia or decreased degradation during shock. Sodium excretion and urine flow increased significantly with RESUS without an associated increase in ANF, suggesting that ANF may not be involved in the early phase of postresuscitation diuresis.

Animals↗
PubMed1988

In vivo regulation of beta-adrenergic receptors on mononuclear leukocytes and heart. Assessment of receptor compartmentation after agonist infusion and acute aortic constriction in guinea pigs.

In animals injected with a bolus of isoproterenol, beta-adrenergic receptors in both mononuclear leukocytes (MNL) and heart were sequestered away from the cell surface, and the time course (0-120 min) and dose-response patterns were similar in the two tissues. In guinea pigs given a constant infusion of isoproterenol, 0.15 mg/(kg.h), down-regulation of total receptor number occurred more quickly and to a greater extent in the MNL than in the heart. We also compared receptor sequestration after aortic constriction-induced acute heart failure. Negligible sequestration (9%) of beta-adrenergic receptors occurred in the MNL of animals treated in this manner, whereas the number of receptors in the sarcolemmal fraction decreased 61%. This selective sequestration of cardiac receptors may result from the action of high concentrations of norepinephrine (which is selective for beta 1 over beta 2 receptors) present at sympathetic nerve-cardiac cell synapses. We conclude that although receptor redistribution occurs similarly in MNL and heart in response to a circulating nonselective agonist, beta-adrenergic receptor redistribution may occur selectively in the heart in response to such stimuli as aortic constriction-induced acute heart failure that activate the sympathetic nervous system.

Adenylyl Cyclases↗
PubMed1988

Endogenous opioid inhibition and facilitation of gonadotropin-releasing hormone release from the median eminence in vitro: potential role of catecholamines.

The intrahypothalamic site(s) of endogenous opioid regulation of GnRH secretion remains to be resolved. Accordingly, we used an in vitro acute incubation system to evaluate GnRH, dopamine (DA), and norepinephrine (NE) release from adult male rat median eminences (MEs) in response to the opiate receptor agonist morphine (MOR) and the opiate receptor antagonist naloxone (NAL). MOR (2 mM) stimulated basal and K+-induced GnRH release from isolated MEs, but 0.25, 5, or 100 microM MOR was without significant effect. NAL (1 mg/ml; 2.8 mM) increased basal GnRH release, but 0.01 mg NAL/ml suppressed basal GnRH release, and neither 0.001 nor 0.1 mg NAL/ml had an appreciable effect. NAL did not significantly alter K+-induced GnRH release. In a separate experiment, 1 mg NAL/ml stimulated but 0.01 mg NAL/ml inhibited basal release of DA and NE from the ME. NAL (1 ng/ml) also decreased K+-induced DA and NE release. The rates of basal and K+-induced DA and NE release were highly correlated with GnRH release during corresponding 0, 0.01, and 1.0 mg/ml NAL treatments in the preceding experiment (r = 0.98 and 0.93, respectively). Thus, 2 mM MOR stimulated but different NAL dosages either stimulated or inhibited GnRH release from isolated MEs, suggesting complex opioid regulation at the level of the GnRH neurosecretory terminals. The precise correlation between GnRH and DA/NE release suggests that the catecholamine terminals close to both GnRH- and endorphin-containing terminals in the ME may mediate this opioid regulation.

Animals↗