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Biomedical subjects

M J McKinley

Publications and source records attributed to M J McKinley.

At least 19 recordsLinked to original sources
PubMed1992

Intravenous angiotensin II induces Fos-immunoreactivity in circumventricular organs of the lamina terminalis.

Conscious rats were infused intravenously with either angiotensin II (30-55 pmol/kg/min), isotonic saline or phenylephrine for 2 h, then killed. Fos was identified by immunohistochemistry in the brains. Fos expression occurred in many neurons of the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) with angiotensin infusion but not with isotonic NaCl or phenylephrine. Fos immunoreactivity was induced in cells in several medullary, hypothalamic and limbic structures with infusions of angiotensin II or phenylephrine at pressor doses. The results suggest that blood-borne angiotensin II at physiological levels causes angiotensin receptive neurons in the subfornical organ and OVLT to express Fos. Activation of baroreceptor pathways may also induce Fos expression at several other sites.

Angiotensin II↗
PubMed1992

Neurons in the median preoptic nucleus of the rat with collateral branches to the subfornical organ and supraoptic nucleus.

A novel pathway between the subfornical organ and the supraoptic nucleus involving the collateral branches of cell bodies situated in the lamina terminalis has been studied. Fluorogold was injected into the supraoptic nucleus and rhodamine-labelled microspheres into the subfornical organ of rats. Nineteen % of neurons in the median preoptic nucleus and 30% of neurons in the OVLT projecting to the subfornical organ also had axons extending to the supraoptic nucleus. These pathways may represent a novel trajectory for the rely of information from the lamina terminalis to the supraoptic nucleus.

Animals↗
PubMed1992

Distribution of hypothalamic, medullary and lamina terminalis neurons expressing Fos after hemorrhage in conscious rats.

The immunohistochemical detection of the protein, Fos, has been used as an anatomical marker of activated neurons. Three conscious rats were hemorrhaged (4 ml, 20-25% of blood volume) and the distribution of Fos-stained neurons was compared to that in 4 rats which did not have blood removed. In hemorrhaged rats, a higher concentration of Fos-stained neurons was present in the lamina terminalis, particularly the subfornical organ and organum vasculosum of the lamina terminalis, and in the supraoptic and paraventricular nuclei of the hypothalamus. In the medulla, Fos-stained neurons were restricted to the nucleus of the tractus solitarius, area postrema and the ventrolateral medulla. We hypothesize that those neurons are involved in mediating the physiological responses to hemorrhage.

Animals↗
PubMed1992

Hemorrhage induces c-fos immunoreactivity in spinally projecting neurons of cat subretrofacial nucleus.

Neuronal expression of c-fos product in the cat rostral ventrolateral medulla was studied by immunohistochemistry. Spinally projecting neurons of the subretrofacial (SRF) nucleus were pre-labeled by retrograde transport of fluorescent latex microspheres from the lumbar cord. In 3 animals which were bled by approximately 25% blood volume from a carotid cannula, 48-62% of SRF-spinal neurons expressed c-fos immunoreactivity. In 2 control animals, the corresponding values were 2% and 4%. The data show that bulbospinal neurons of presumed vasomotor function express c-fos in response to hemorrhage.

Animals↗
PubMed1992

Efferent neural pathways of the lamina terminalis subserving osmoregulation.

Studies in rats and sheep show that neurons in the CVOs of the lamina terminalis provide extensive neural input to the vasopressin-containing cells of the supraoptic nucleus. This input is both by direct pathways and via a synapse in the MnPO which also has projections to the vasopressin-containing cells of the SON. Neurons throughout the lamina terminalis (including possible osmoreceptors in the OVLT and subfornical organ) are activated by systematic hypertonicity. It is likely that in response to hypertonicity they signal the SON and PVN to release vasopressin and elsewhere to elicit other osmoregulatory responses such as thirst and the excretion of sodium.

Animals↗
PubMed1992

Thirst and brain angiotensin in cattle.

Cows that were normally hydrated or deprived of water were given intravenous or intracerebroventricular (icv) infusions of angiotensin I converting-enzyme inhibitors (CEI) or angiotensin II antagonists. Normally hydrated Na-deficient cows increased water intake in a dose-related manner in response to icv infusion of angiotensin I (n = 5). The response to 3 micrograms/h angiotensin I was abolished by concurrent icv infusion of the CEI captopril at 3 mg/h but not by intravenous infusion of captopril at 120 mg/h, which reduced Na appetite (n = 5). The icv infusion of captopril at 12 mg/h did not reduce the water intake of cows that were water restricted for 26.5 h (n = 4) or water restricted and Na deficient (n = 4). The icv infusion of the more lipophilic CEI ramipril at 3 mg/h (n = 7) did not reduce the water intake of normally hydrated or dehydrated cows but reduced the "need-free" intake of Na solution by dehydrated cows. The icv infusion of the nonpeptide antagonist Du Pont 753 at 3 mg/h (n = 7) reduced water intake in dehydrated cows. The results indicate that brain angiotensin may be involved in thirst in cattle. The data suggest that this brain angiotensin II may be formed by a pathway that does not include converting enzyme and that is sited inside the blood brain barrier, possibly in the median preoptic nucleus.

Angiotensin I↗
PubMed1992

Atrial natriuretic peptide does not alter cerebrospinal fluid formation in sheep.

Because the choroid plexus has been shown to have a high density of atrial natriuretic peptide (ANP) binding sites, we investigated the effect of intracerebroventricular and intravenous administrations of ANP on cerebrospinal fluid (CSF) formation. CSF formation rate was measured in conscious sheep with a dye-dilution method using blue dextran 2000 as an indicator substance. During the experiment animals were partially restrained in a sling, and their ventricular systems were perfused with artificial CSF containing the indicator substance. ANP (alpha-human ANP) administered centrally at rates of 0.015-15 ng/min, resulting in CSF ANP concentrations ranging from physiological to pharmacological CSF hormone levels, was found not to influence CSF formation. Similarly, intravenous administration of ANP at a rate of 10 ng.kg-1.min-1 did not affect CSF formation, i.e., decreases in CSF formation rate in all experiments involving ANP administration were not significantly different from those observed in time control experiments. Our results suggest that ANP does not significantly affect CSF production in sheep. It is possible that the lack of effect of ANP on CSF formation is associated with the predominance in the choroid plexus of clearance receptors over biologically active receptors.

Animals↗
PubMed1992

Behavioral and tissue responses to severe phosphorus depletion in cattle.

Two-year-old Aberdeen Angus heifers were depleted of phosphorus (P) by loss of phosphate in saliva from a parotid gland fistula combined with a low-P diet. The inorganic phosphate concentrations (Pi) of plasma, parotid saliva, ruminal fluid, and feces were reduced, but cerebrospinal fluid Pi was unaltered. Plasma Pi fell to less than 1.0 mM in 12 wk, and the cows displayed an avid appetite for old bones. P-deficient cows preferred old weathered bones to fresh bones until the latter had aged for approximately 1.5 yr. They did not eat blood, peritoneal fat, or meat, fresh or aged for 2-3 yr. They did not eat Na or Ca phosphate salts or bone heated to greater than 250 degrees C. P-replete cows did not take or eat bones. The behavioral effects of P deficiency were associated with failure to gain body weight and maintain condition, significant bone changes indicated by reduced bone weight and specific gravity, osteopenia indicated by radiology, evidence of reduced bone formation indicated by plasma osteocalcin levels and histology, and abnormal estrous cycles. Prolonged P deficiency was associated with increased plasma concentrations of total Ca and 1,25-dihydroxyvitamin D and reduced plasma concentrations of parathyroid hormone.

Animals↗
PubMed1992

Periventricular lesions block natriuresis to hypertonic but not isotonic NaCl loads.

The renal excretion of Na and water after an intravenous load of hypertonic or isotonic saline was studied in conscious sheep in which periventricular tissue in the region of the lamina terminalis had been ablated. Hypertonic saline (3.4-4.2 mmol/l) was infused at 0.06 mmol.kg-1.min-1 for 40 min into the jugular vein. Plasma Na concentration increased 5 mmol/l, and in normal sheep a natriuresis and increase in glomerular filtration rate ensued during the next hour. Such a natriuretic effect did not occur in sheep with periventricular lesions. By contrast, intravenous infusion of isotonic saline (30 ml/kg body wt, i.e., 0.23 mmol.kg-1.min-1 for 20 min) caused similar increase in renal Na excretion in normal sheep and sheep with periventricular lesions. When the same intravenous load of NaCl (0.23 mmol.kg-1.min-1 for 20 min) was administered as hypertonic 20% NaCl, ablation of periventricular tissue greatly impaired the excretion of this Na load. We suggest that the periventricular tissue in the region of the lamina terminalis has a role in regulation of renal Na excretion in conditions where the plasma Na concentration increases. This tissue is also involved in osmoregulatory thirst and vasopressin secretion. We further propose that increased renal Na excretion in response to hypernatremia is another cerebrally mediated osmoregulatory response.

Animals↗
PubMed1992

Common aspects of the cerebral regulation of thirst and renal sodium excretion.

It has been shown that several mammalian species increase the excretion of sodium in urine as they become dehydrated. This dehydration-induced natriuresis occurs despite simultaneous hypovolemia, and it can be blocked by an experimentally-induced reduction in the sodium concentration of CSF, or by ablation of the periventricular tissue in the vicinity of the lamina terminalis. These two experimental procedures also disrupt thirst and vasopressin secretion. There may therefore be common features involved in the central control of osmoregulatory thirst, vasopressin secretion and sodium excretion. Experimental evidence in sheep suggests that whenever the tonicity of body fluids increases, a centrally mediated natriuretic mechanism is engaged. This cerebral natriuretic mechanism may contribute along with other influences such as the extracellular fluid volume, aldosterone and atrial natriuretic peptide, to determine the rate of sodium excretion by kidneys. The efferent pathway from brain to kidney mediating osmoregulatory natriuresis is not known. It is probably hormonal, because renal denervation does not disrupt such natriuresis.

Animals↗
PubMed1992

Clostridium cadaveris: an unusual cause of spontaneous bacterial peritonitis.

Bacterial peritonitis has been known to complicate severe liver disease. Aerobic organisms are responsible for the vast majority of cases, whereas anaerobic bacteria are responsible for less than 5% of all cases reported in the literature. We now report a case of Clostridium cadaveris anaerobic bacterial peritonitis in a 58-yr-old female, an organism that to our knowledge has not been previously implicated as an infectious agent in this entity.

Clostridium Infections↗
PubMed1991

Localization and characterization of angiotensin II receptor binding sites in the human basal ganglia, thalamus, midbrain pons, and cerebellum.

Angiotensin II (Ang II) binding sites were localized in the thalamus, basal ganglia, midbrain, and pons of the human central nervous system by in vitro autoradiography, employing 125I-[Sar1, Ile8]angiotensin II as the radioligand. High-density binding occurs in the substantia nigra pars compacta, the interpeduncular nucleus and two of the raphe nuclei, the raphe magnus, and median raphe nucleus. Moderate densities occur in the caudate nucleus, putamen, bed nucleus of the stria terminalis, rostral linear nucleus, caudal linear nucleus, dorsal and paramedian raphe nuclei, locus coeruleus, and region of the subcoeruleus, oral dorsal paramedian nucleus, and A5/periolivary region. Low levels occur in the region between the subthalamic nucleus and the zona incerta, the mediodorsal thalamic nucleus, the central gray, the lateral and medial parabrachial nuclei, and the molecular layer of the cerebellum. The high density of Ang II receptor binding in the substantia nigra occurs over pigmented, presumably dopaminergic, neurons. The binding in this site, and in the striatum, is not observed in any of the other species we have studied. It displays similar pharmacological characteristics to the Ang II receptor binding site in other regions of the human brain. Overall we demonstrate a discrete pattern of Ang II receptor binding sites in the human brain, which shows a high correlation with the distribution observed in other mammalian species.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1991

Intravenous hypertonic saline induces Fos immunoreactivity in neurons throughout the lamina terminalis.

Expression of Fos, the protein product of c-fos, was studied immunohistochemically in the forebrain of rats infused intravenously with hypertonic solutions. Intravenous 1.5 or 0.75 mol/l NaCl or 1.2 mol/l sucrose in 0.15 mol/l NaCl, but not isotonic 0.15 mol/l NaCl, caused increased Fos expression in the hypothalamic paraventricular and supraoptic nuclei and throughout the lamina terminalis (organum vasculosum laminae terminalis, median preoptic nucleus and subfornical organ). These results show that neurons in the lamina terminalis are activated by physiological increases in plasma tonicity and support an involvement of the lamina terminalis in osmoregulation.

Animals↗
PubMed1991

Projections from the subfornical organ to the supraoptic nucleus in the rat: ultrastructural identification of an interposed synapse in the median preoptic nucleus using a combination of neuronal tracers.

The subfornical organ, along with other regions of the lamina terminalis, may contain osmoreceptors and is likely to be a site of action of blood-borne angiotensin II. The neural pathways by which these stimuli lead to vasopressin secretion, have been suggested to extend from the subfornical organ to hypothalamic sites of vasopressin production either directly or via synapses in an intervening nucleus such as the median preoptic nucleus. In the present study, cholera toxin conjugated to horseradish peroxidase (CT/HRP) or colloidal gold (CT/Au) has been injected, respectively, into the subfornical organ and supraoptic nucleus of the same animal. The anterograde and retrograde transport of the toxin from these two sites has made possible the identification, at the ultrastructural level, of a synapse in the median preoptic nucleus interposed in the pathway between the subfornical organ and the supraoptic nucleus. Moreover, the presence of retrogradely transported CT/HRP and CT/Au in the same neurone in the median preoptic nucleus indicates that some neurones in this nucleus have axons with collateral branches to both the subfornical organ and supraoptic nucleus. Either or both of these pathways may transmit information related to the tonicity of the blood or circulating levels of angiotensin II to sites in the hypothalamus.

Animals↗
PubMed1991

Median preoptic nucleus projections to vasopressin-containing neurones of the supraoptic nucleus in sheep. A light and electron microscopic study.

It has been postulated that osmoreceptors are situated in either or both of two components of the lamina terminalis, the subfornical organ (sfo) and organum vasculosum laminae terminalis (ovlt) and that information from these sites may be relayed to the hypothalamus directly or via a synapse in the median preoptic nucleus (mnpo). We have investigated the nature of projections from the mnpo to vasopressin (AVP)-containing neurones in the hypothalamus. Microinjections of horseradish peroxidase-wheat germ agglutinin (HRP-WGA) have been made into the mnpo and supraoptic nucleus (son) of the sheep. These injections indicated that in the sheep, as in the rat, the mnpo shares a reciprocal innervation with the sfo and ovlt. Furthermore, the most extensive efferent outflow of the mnpo is to the son, with lesser projections directed to the pvn and other hypothalamic sites. When examined at the electron microscopic level, fibres projecting from the mnpo to the son were found to form synapses with immunocytochemically identified AVP neurones. It is suggested that this pathway is one of the major routes by which information from putative osmoreceptors in the lamina terminalis is conveyed to AVP neurones in the hypothalamus.

Animals↗
PubMed1991

Angiotensin converting enzyme in the monkey (Macaca fascicularis) brain visualized by in vitro autoradiography.

Angiotensin converting enzyme is localized in the monkey (Macaca fascicularis) brain by in vitro autoradiography using the radiolabelled inhibitor, [125I]351A. This radioligand binds with high affinity and specificity to monkey cortical sections. Specific inhibitors of converting enzyme, lisinopril and perindoprilat complete for the radioligand binding to monkey cortex sections with inhibitory constants of 10 nM. High concentrations of angiotensin converting enzyme occur in most components of the basal ganglia including the caudate nucleus, putamen, the internal and external globus pallidus, nucleus accumbens, ventral pallidum and the reticular part of the substantia nigra. The distribution of converting enzyme in the caudate nucleus and putamen is heterogeneous, with prominent patches of higher activity. The patches in the caudate nucleus correspond closely with the acetylcholinesterase-poor striosomes. In the hypothalamus, very high levels of angiotensin converting enzyme occur in the median eminence and the pituitary stalk and high concentrations occur in the supraoptic and suprachiasmatic nuclei. Moderate, diffuse binding is observed in the median preoptic nucleus, the medial preoptic area, and in the anterior, lateral, ventromedial, posterior and arcuate nuclei. In the circumventricular organs, the subcommissural and subfornical organs exhibit high levels of angiotensin converting enzyme. The organum vasculosum of the lamina terminalis and the pineal body display moderate enzyme activities whereas the area postrema is devoid of labelling. The interpeduncular nucleus and, in the hippocampal formation, the molecular layer of the dentate gyrus are also intensely labelled. High levels of angiotensin converting enzyme activity are also detected throughout the cerebral cortex with laminations of higher activity corresponding to cell dense layers of the cortex. Layered binding is also present in the cerebellar cortex, with the most intense labelling in the molecular layer. Moderate concentrations of converting enzyme also occur in the paraventricular, medial habenula, lateral habenula and central median nuclei of the thalamus, the amygdala, the central gray, the locus coeruleus, the parabrachial nucleus and dorsal tegmental nucleus. The dorsal vagal complex, inferior olivary nucleus and the caudal subnucleus of the spinal trigeminal nucleus all display high levels of binding. Moderate, diffuse labelling is found throughout the reticular region and is also present in the gracile and cuneate nuclei. Although the overall distribution of angiotensin converting enzyme in the monkey brain resembles that in the rat, there are some striking differences. These include the high levels of binding throughout the monkey cerebral cortex and in the interpeduncular and suprachiasmatic nuclei.

Acetylcholinesterase↗