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Biomedical subjects

M J Sole

Publications and source records attributed to M J Sole.

At least 73 records · Page 4Linked to original sources
PubMed1986

An active pathway for serotonin synthesis by renal proximal tubules.

Serotonin (5HT) has significant effects on renal metabolism and glomerular function and is a potent renal vasoconstrictor. In this study we describe and localize a highly active biosynthetic pathway for serotonin in the kidney. Rat kidneys were dissected into cortical and medullary fractions; in some experiments the cortex was also separated into subfractions enriched with glomeruli or proximal tubules. Serotonin and tryptophan hydroxylase (TyOH) were measured by radioenzymatic techniques. (table; see text) Renal denervation did not alter tryptophan hydroxylase activity. In kidneys from human cadaveric donors, cortical tryptophan hydroxylase (4.13 +/- 0.68 nM/30 min/g) exceeded that in the medulla (1.96 +/- 0.86 nM/30 min/g). Aromatic L-amino acid decarboxylase, the remaining enzyme for serotonin synthesis, is present in both rat renal cortex and medulla; however, we found 15-fold greater decarboxylase activity in proximal tubular (2070 nM/30 min/g) as compared to glomerular (131 nM/30 min/g) subfractions. We were able to demonstrate that under physiological conditions, free urine serotonin reflects actual biosynthesis by the kidney. Thus, although serotonin stores retained by the kidney appear small and relatively localized to the medulla, the enzymatic activity for the synthesis of serotonin in the kidney is comparable to that in the brain, with the complete pathway localized to renal cortical proximal tubules. These data suggest that further studies of renal serotonin metabolism may contribute to our understanding of renal function in health and disease.

Animals↗
PubMed1986

Favorable effects of pindolol in dilated cardiomyopathy.

We describe the clinical course of a patient with tachycardia at rest, biopsy proven dilated cardiomyopathy, and moderately severe left ventricular systolic dysfunction. Short-term use of pindolol produced a significant fall in heart rate and cardiac output at rest and during exercise. However, after addition of pindolol to the patient's previous regimen of digoxin and furosemide, he made a rapid clinical recovery and has maintained clinical improvement during the last four years of follow-up. The pattern of clinical response suggests that pindolol may have contributed substantially to this patient's recovery.

Cardiomyopathy, Dilated↗
PubMed1985

Digitoxin therapy partially restores cardiac catecholamine and brain serotonin metabolism in congestive heart failure.

The effect of therapeutic doses of digitalis in modifying neural activity has been the subject of considerable controversy. In earlier studies we reported an increase both in serotonergic activity in the posterior hypothalamus and pons-medulla and in cardiac sympathetic tone in the failing cardiomyopathic hamster. In this study we examine the effects of doses of digitoxin, known to be therapeutic for hamster heart failure, on monoamine neurotransmitter metabolism in the brain and heart during the cardiomyopathy. Both digitoxin and ASI-222, a polar amino-glycoside which does not cross the blood-brain barrier, given either acutely (6 mg/kg ip) or chronically (2 mg/kg/day ip for 10 days), normalized the failure-induced increase in serotonin turnover in the pons-medulla but had no effect on the changes in the posterior hypothalamus. Digitoxin therapy also reduced cardiac and adrenal sympathetic activity partially restoring cardiac catecholamine stores. In order to more clearly define the pathways involved we measured serotonin (microgram/g protein) in 18 brain nuclei after 10 days of digitoxin or vehicle treatment. Heart failure was associated with an increase in serotonin in five nuclei: the mammillary; bodies, ventromedial, periventricular and paraventricular nuclei of the hypothalamus, and the centralis superior nucleus of the raphe. Digitoxin therapy completely normalized the changes in the centralis superior and ventromedialis nuclei; neither congestive heart failure nor digitoxin affected serotonin levels in other nuclei. We conclude that there is an increase in activity in specific brain serotonergic nuclei in congestive heart failure. Digitalis reduces cardiac sympathetic tone and restores the changes in two of these nuclei: the ventromedial and the centralis superior.+2

Animals↗
PubMed1984

Sudden infant death syndrome: increased carotid-body dopamine and noradrenaline content.

Carotid bodies from infants dying of sudden infant death syndrome contained significantly higher concentrations of dopamine (10-fold) and noradrenaline (3-fold) than those from age-matched control infants. Administration of dopamine inhibits respiration by direct action on the carotid body, and it is suggested that the elevated levels of endogenous catecholamines found in victims of sudden infant death syndrome may compromise the normal function of the carotid body, particularly the ventilatory response to hypoxia.

Carotid Body↗
PubMed1984

Free tyrosine levels of rat brain and tissues with sympathetic innervation following administration of L-tyrosine in the presence and absence of large neutral amino acids.

The tyrosine concentration of fasted rats was measured in plasma, brain and tissues receiving sympathetic innervation after L-tyrosine (200 mg/kg) was administered alone or in the presence of an equimolar cocktail containing isoleucine, leucine and valine. In the samples taken at 15, 30, 45, 60, 120 or 180 minutes, the highest concentrations of L-tyrosine were observed in plasma, heart, adrenal gland and kidney at 15 minutes, but in interscapular brown adipose tissue at 15 and 30 minutes and in brain at 15-60 minutes. The decline from peak concentrations was slower in brain, kidney and interscapular brown adipose tissue than in plasma, but in all tissues examined, control levels of free tyrosine were attained by 180 minutes postadministration . Competing large neutral amino acids reduced the maximal uptake of tyrosine in the brain by 48% but had no effect in the other tissues examined.

Adipose Tissue, Brown↗
PubMed1983

The identification of specific serotonergic nuclei inhibited by cardiac vagal afferents during acute myocardial ischemia in the rat.

Cardio-cardiac autonomic reflexes mediated by the cardiac vagus during acute myocardial infarction play an important role in determining post-infarction hemodynamic function and the susceptibility of the infarcting heart to lethal arrythmias. In an earlier study we had demonstrated that serotonin-containing neurons in the brain participate in the mediation of these reflexes following left coronary artery ligation in the rat. In this study we identify brain serotonin nuclei involved. The accumulation of serotonin was measured in 19 brain nuclei from rats treated with pargyline, a monoamine oxidase inhibitor. The rats were subjected to either left coronary artery ligation or sham operation with or without bilateral cervical vagotomy or lidocaine applied topically only to the left ventricle. Serotonin accumulation was markedly reduced in the nucleus hypothalamicus posterior, nucleus raphe magnus and nuclei-raphe medianus-centralis superior in the rats subjected to coronary artery ligation as opposed to sham operation; no other brain regions were affected. The topical application of lidocaine to the left ventricle or vagotomy completely obviated the ligation-induced decrease in serotonin turnover. We conclude that there is an inhibition of serotonergic activity in the nucleus hypothalamicus posterior, nucleus raphe magnus and nuclei raphe medianus-centralis superior following left ventricular myocardial infarction in the rat. The afferent signal arises from receptors in the left ventricle and is conducted by the vagus.

Animals↗
PubMed1983

The influence of oral tyrosine and tryptophan feeding on plasma catecholamines in man.

We investigated the effects of oral tyrosine (7.5 g/day) and oral tryptophan (3 g/day) feeding with regular meals in normal male volunteers using a double-blind cross-over design with a "run in" period for acclimatization. Oral tyrosine feeding significantly decreased both free and conjugated plasma norepinephrine concentrations while oral tryptophan feeding did not have such an effect. Since alpha adrenergic stimulation in certain areas of the CNS has been shown to decrease peripheral sympathetic tone, we postulate that dietary tyrosine supplementation in man causes an increase in brain catecholaminergic activity which in turn leads to a decrease in peripheral sympathetic activity as evidenced by the decrease in plasma catecholamines.

Adult↗
PubMed1983

Tissue catecholamines in obstructive nephropathy and acute uremia in the rat.

Previous studies have shown that the 24-h unilateral ureteral obstructed kidney (UUO) responds to acute renal denervation after relief of obstruction with an increase in glomerular filtration rate (GFR), renal plasma flow (RPF), natriuresis, and diuresis, while the 24-h bilateral ureteral obstructed kidney (BUO), undergoing postobstructive diuresis after relief of obstruction, shows no response to acute denervation. In the present study, renal tissue norepinephrine (NE) content and concentration were found to be markedly decreased in the BUO kidney suggesting partial renal denervation, while renal NE content was normal in the UUO kidney. The decrease in renal NE content in the BUO kidney was organ specific since myocardial NE was not affected, and was not due to acute uremia, since rats made uremic by 24 h of total intravenous urine reinfusion showed no change in renal NE content. Renal dopamine content was markedly increased in the UUO kidney, perhaps as a result of renal decarboxylation of dopa and failure of excretion, while renal and myocardial epinephrine content were increased in the BUO and urine reinfused groups, both of which were subjected to the stress of acute uremia. The decrease in renal NE content in the kidney undergoing postobstructive diuresis after relief of 24-h BUO probably indicates damage to sympathetic nerve terminals by high intrarenal pressure during BUO and suggests that partial renal denervation could contribute to the functional changes observed in this experimental model.

Acute Disease↗
PubMed1983

Nonenzymatic separation of myocardial cell nuclei from whole heart tissue.

A simple and rapid nonenzymatic method has been developed to isolate myocardial cell nuclei from whole heart tissue. This method consists of a controlled disruption of cells followed by isopycnic gradient centrifugation. We have reviewed and compared our method to others more lengthy and laborious. By using a number of criteria, such as morphometric measurements, chemical composition, functional studies, specific nuclear protein markers, and mathematical analysis, we show that the nonenzymatic digestion method provides a most useful technique for the study of the biochemistry of the myocardial cell nucleus.

Aging↗
PubMed1982

Simultaneous measurement of 5-hydroxytryptophan and L-dihydroxyphenylalanine by high-performance liquid chromatography with electrochemical detection. Measurement of serotonin and catecholamine turnover in discrete brain regions.

A sensitive method, using reversed-phase high-performance liquid chromatography with electrochemical detection, which allows the measurement of both 5-hydroxytryptophan and L-dihydroxyphenylalanine is described. This method, used in conjunction with the administration in vivo of an L-aromatic amino acid decarboxylase inhibitor, allows the simultaneous measurement of serotonin and catecholamine synthesis rates in small discrete brain regions.

5-Hydroxytryptophan↗
PubMed1982

The identification of specific brain nuclei in which catecholamine turnover is increased by left ventricular receptors during acute myocardial infarction in the rat.

Central catecholaminergic nerves have been shown to participate in the integration of cardio-cardiac reflexes induced by coronary artery ligation in the rat. In this study we measured the turnover of dopamine, norepinephrine and epinephrine in microdissected brain regions to identify some of the specific neural loci involved in this integration. Three groups of rats, treated with alpha-methyltyrosine, an inhibitor of catecholamine biosynthesis were examined: left coronary artery ligation, left coronary artery ligation with the left ventricle painted with lidocaine, and sham operation. An untreated group of resting rats was also examined. Dopamine, norepinephrine and epinephrine turnover was increased in ligated rats in nucleus tractus solitarius (right and left), nucleus commissuralis, A1-region, locus coeruleus, nucleus cuneatus, and area postrema in the pons-medulla and nucleus dorsomedialis in the hypothalamus. Norepinephrine and dopamine (but not epinephrine) turnover was increased in nucleus ambiguus in the brain stem and nucleus paraventricularis in the hypothalamus. A ligation-induced increase in norepinephrine turnover, alone, was exhibited by the A2-region and nucleus gigantocellularis in the medulla and nucleus supraopticus and nucleus hypothalamicus posterior in the hypothalamus. Dopaminergic nerves to the nucleus gigantocellularis appeared to be inhibited following coronary ligation. The catecholamine stores of 11 nuclear regions were not influenced by coronary artery occlusion. Topical lidocaine, applied to the ischemic left ventricle, only, of ligated rats, completely restored regional brain catecholamine turnover to that found in sham-operated animals. In conclusion, we have identified discrete loci in the brain in which catecholamine turnover (as measured by alpha-methyltyrosine induced disappearance) is increased by the stimulation of left ventricular receptors during acute myocardial ischemia in the rat.

Animals↗
PubMed1982

Neural and extraneural catecholamine production by rat kidneys.

Catecholamine production by innervated kidneys was examined by radioenzymatic assay of norepinephrine (NE), epinephrine (E), and dopamine (DA) in lymph, urine, arterial plasma, and renal venous plasma of hydropenic rats. Denervation reduced NE excretion in urine by 18% and both NE and DA efflux in renal venous plasma by 37 and 30%, respectively. The kidney's handling of E was unaltered by denervation. Renal nerves added 1.0 +/- 0.2 ng/min to the efflux of NE in urine and renal venous plasma. Denervation reduced this efflux to -0.1 +/- 0.2 ng/min. DA efflux from innervated kidneys was 1.4 +/- 0.2 ng/min but only half came from renal nerves, as denervated kidneys released 0.7 +/- 0.1 ng/min. Renal lymph from innervated kidneys contained slightly more NE but less DA than arterial plasma. We conclude that renal nerves release both NE and DA but that half of the renal contribution to urine and renal venous plasma DA efflux comes from extraneuronal tissue. Renal lymph NE and DA concentrations are similar to those in arterial plasma, suggesting that peritubular concentrations are low everywhere except within renal clefts.

Animals↗
PubMed1981

Inhibition of serotonin synthesis within the medulla and posterior hypothalamus by cardiac vagal afferents during acute myocardial ischemia in the rat.

Serotonin synthesis, as estimated by the accumulation of 5-hydroxytryptophan 25 min following aromatic-L-amino acid decarboxylase inhibition, was measured in the medulla, pons-midbrain and posterior and anterior hypothalamus of rats subjected to left coronary artery ligation and their sham-operated controls. Left coronary artery ligation led to reduction in the rate of serotonin synthesis in the medulla and posterior hypothalamus. The topical administration of lidocaine to the left ventricle or vagotomy completely obviated these occlusion-induced changes. We conclude that there is an inhibition of serotonergic activity in the medulla and posterior hypothalamus after left coronary artery occlusion in the rat. The afferent signal arises from receptors in the ischemic left ventricle and is conducted by the vagus.

Afferent Pathways↗
PubMed1981

Analysis of non-histone chromatin proteins in porcine malignant hyperthermia.

Non-histone chromatin proteins (NHCP) were isolated from skeletal muscle, left ventricle and liver of swine susceptible to malignant hyperthermia and from controls. These proteins were extracted with phenol buffers and fractionated by polyacrylamide gel electrophoresis. Isoelectrofocusing gel electrophoresis revealed quantitative differences in NHCP from skeletal muscle between disease and control groups. The high resolution of proteins by two-dimensional polyacrylamide gel electrophoresis showed a relative similarity between skeletal muscle, heart and liver although some differences could be discerned. Non-histone chromatin proteins of molecular weight 35,000-45,000, focusing between pH7 and 9, were increased in skeletal muscle nuclei derived from malignant hyperthermia-susceptible swine. These proteins appear to be important in the maturation of messenger RNA. No alterations were seen in either heart or liver. We conclude that an increase in NHCP which is associated with the processing of messenger RNA, may be important in the phenotypic expression in skeletal muscle of malignant hyperthermia in swine.

Animals↗
PubMed1981

Adrenergic regulation of glucagon and insulin secretion during immobilization stress in normal and spontaneously diabetic BB rats.

To test for a possible role of adrenergic mechanisms in the altered glucagon secretion in the spontaneously diabetic "BB" rat, the responses of glucose, insulin, and glucagon to adrenergic blocking agents in diabetic and normal rats were compared at rest and during 2 h of immobilization stress. In unstressed normal rats, phentolamine alone caused a 20 mg/dl fall in glycemia, 1.2 ng/ml rise in insulin (IRI), and no change in glucagon (IRG), whereas the only effect of propranolol was a minor rise in glycemia. Stress caused increments in glycemia of 72 mg/dl and in IRG of 94 pg/ml, and no change in IRI. Phentolamine significantly attenuated the stress-related increments, and IRI increased by the same amount as in the unstressed state. Propranolol exhibited no statistically significant effects on the response to stress. These findings are consistent with alpha-adrenergic stimulation of IRG and suppression of IRI secretion. In unstressed diabetic rats (mean time 0 glycemia, 431 mg/dl), propranolol caused only a small rise in glycemia, whereas phentolamine induced marked increments of glycemia (131 mg/dl) and IRG (116 pg/ml). Stress alone did likewise (189 mg/dl, 122 pg/ml) as did stress with the phentolamine (271 mg/dl, 144 pg/ml). However propranolol significantly attenuated the stress-induced increments in glycemia (88 mg/dl) and IRG (82 pg/ml). Thus both alpha- and beta-adrenergic receptors influence IRG secretion in the diabetic rats. An in vivo model for elucidating neural control of glucoregulation has been developed that is independent of cardiovascular fitness.

Adrenal Glands↗