Neuroendocrine self-control: dendritic release of vasopressin.
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Animals↗
Biomedical subjects
Michael J McKinley
Publications and source records attributed to Michael J McKinley.
Differential effects of intravenous hyperosmotic solutes on drinking latency and c-Fos expression in the circumventricular organs and hypothalamus of the rat.
Hyperosmotic intravenous infusions of NaCl are more potent for inducing drinking and vasopressin (AVP) secretion than equally osmotic solutions of glucose or urea. The fact that all three solutes increased cerebrospinal fluid osmolality and sodium concentration led the investigators to conclude that critical sodium receptors or osmoreceptors for stimulating drinking and AVP secretion were outside the blood-brain barrier (BBB) in the circumventricular organs (CVOs). We tested an obvious prediction of this hypothesis: that all three solutes should increase c-Fos-like immunoreactivity (Fos-ir) inside the BBB, but that only NaCl should increase Fos-ir in the CVOs. We gave intravenous infusions of 3.0 Osm/l NaCl, glucose, or urea to rats for 11 or 22 min at 0.14 ml/min and perfused the rats for assay of Fos-ir at 90 min. Controls received isotonic NaCl at the same volume. Drinking latency was measured, but water was then removed. Drinking consistently occurred with short latency during hyperosmotic NaCl infusions only. Fos-ir in the forebrain CVOs, the subfornical organ, and organum vasculosum laminae terminalis was consistently elevated only by hyperosmotic NaCl. However, all three hyperosmotic solutes potently stimulated Fos-ir in the supraoptic and paraventricular nuclei of the hypothalamus inside the BBB. Hyperosmotic NaCl greatly elevated Fos-ir in the area postrema, but even glucose and urea caused moderate elevations that may be related to volume expansion rather than osmolality. The data provide strong support for the conclusion that the osmoreceptors controlling drinking are located in the CVOs.
Animals↗
Human medullary responses to cooling and rewarming the skin: a functional MRI study.
A fall in skin temperature precipitates a repertoire of thermoregulatory responses that reduce the likelihood of a decrease in core temperature. Studies in animals suggest that medullary raphé neurons are essential for cold-defense, mediating both the cutaneous vasoconstrictor and thermogenic responses to ambient cooling; however, the involvement of raphé neurons in human thermoregulation has not been investigated. This study used functional MRI with an anatomically guided region of interest (ROI) approach to characterize changes in the blood oxygen level-dependent (BOLD) signal within the human medulla of nine normal subjects during non-noxious cooling and rewarming of the skin by a water-perfused body suit. An ROI covering 4.9 +/- 0.3 mm(2) in the ventral midline of the medulla immediately caudal to the pons (the rostral medullary raphé) showed an increase in BOLD signal of 3.9% (P < 0.01) during periods of skin cooling, compared with other times. Overall, that signal showed a strong inverse correlation (R = 0.48, P < 0.001) with skin temperature. A larger ROI covering the internal medullary cross section at the same level (area, 126 +/- 15 mm(2)) showed no significant change in mean BOLD signal with cooling (+0.2%, P > 0.05). These findings demonstrate that human rostral medullary raphé neurons are selectively activated in response to a thermoregulatory challenge and point to the location of thermoregulatory neurons homologous to those of the raphé pallidus nucleus in rodents.
Adult↗
Water intake and the neural correlates of the consciousness of thirst.
Thirst and resultant water drinking can arise in response to deficits in both the intracellular and extracellular fluid compartments. Inhibitory influences mediating the satiation of thirst also are necessary to prevent overhydration. The brain regions that underpin the generation or inhibition of thirst in these circumstances can be categorized as sensory, integrative, or cortical effector sites. The anterior cingulate cortex and insula are activated in thirsty human beings as shown by functional brain-imaging techniques. It is postulated that these sites may be cortical effector regions for thirst. A major sensory site for generating thirst is the lamina terminalis in the forebrain. Osmoreceptors within the organum vasculosum of the lamina terminalis and subfornical organ detect systemic hypertonicity. The subfornical organ mediates the dipsogenic actions of circulating angiotensin II and relaxin. Major integrative sites are the nucleus of the tractus solitarius, the lateral parabrachial nucleus, the midbrain raphé nuclei, the median preoptic nucleus, and the septum. Despite these advances, most of the neural pathways and neurochemical mechanisms subserving the genesis of thirst remain to be elucidated.
Animals↗
Postnatal development of orexin-A and orexin-B like immunoreactivities in the Eastern grey kangaroo (Macropus giganteus) hypothalamus.
The Eastern grey kangaroo (Macropus giganteus) is a marsupial, which is born in an extremely undeveloped state and has a long suckling period in the mother's pouch. In the present study, we examined the immunoreactivities of orexin-A (OXA) and orexin-B (OXB) in the hypothalamus of the Eastern grey kangaroo during the preweaning period, postweaning period and adulthood. In the preweaning period, only a few OXA- and OXB-like immunoreactive (LI) neurons and fibers were present and the intensity of staining was very weak. In the postweaning period, there was a pronounced increase in the numbers of OXA- and OXB-LI neurons and fibers and the intensity of the immunoreactivity was considerably stronger in comparison to the preweaning period. In the adult, the numbers of OXA- and OXB-LI neurons and fibers appeared to be slightly increased and the intensity was slightly stronger in comparison to the postweaning period. At all time periods, the distributions of OXA- and OXB-LI neurons was similar. The postnatal development of hypothalamic orexin neurons may be associated with developmental changes, including feeding behavior.
Animals↗
Cortical, thalamic, and hypothalamic responses to cooling and warming the skin in awake humans: a positron-emission tomography study.
Thermoregulatory mechanisms are remarkably efficient, ensuring minimal temperature variation within the core of the human body under physiological conditions. Diverse afferent and efferent neural pathways contribute to the monitoring of core and skin temperature, generation of heat, and control of thermal exchange with the external environment. We have investigated the cortical, thalamic, and hypothalamic responses to cooling and warming by using positron-emission tomography activation imaging of subjects clad in a water-perfused suit, which enabled rapid change of their skin-surface temperature. Human brain regions that respond to changes in skin temperature have been identified in the somatosensory cortex, insula, anterior cingulate, thalamus, and hypothalamus, with evidence that the hypothalamic response codes for the direction of temperature change. We conclude that signals from thermosensors in the skin providing crucial afferent information to the brain are integrated with signals from central thermosensors, resulting in thermoregulatory responses that maintain core temperature within a remarkably narrow range.
Adult↗
Angiotensinogen and angiotensin-converting enzyme gene copy number and angiotensin and bradykinin peptide levels in mice.
OBJECTIVE: To test the hypothesis that changes in gene expression that may accompany angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) gene polymorphism cause alteration in angiotensin and bradykinin peptide levels. DESIGN: Mice with one or two genes for AGT and ACE allow assessment of the effects of modest alteration in AGT and ACE gene expression on angiotensin and bradykinin peptide levels. METHODS: Angiotensin and bradykinin peptides were measured in the blood, kidney, heart, lung, adrenal, brain, and aorta of mice that were either wild-type (+/+), heterozygous (+/-) or null (-/-) for either the AGT or ACE gene. RESULTS: Angiotensin I and angiotensin II were not detectable in blood or tissues of AGT -/- mice, which had increased bradykinin levels in kidney and lung. ACE -/- mice had markedly reduced angiotensin II levels and increased bradykinin levels in blood and tissues. However, despite reduced AGT and ACE gene expression, angiotensin and bradykinin peptide levels in AGT and ACE +/- mice were no different from the levels in wild-type mice. CONCLUSION: Although the AGT and ACE genes are fundamental determinants of angiotensin and bradykinin peptide levels, compensatory mechanisms attenuate the effect of modest change in AGT and ACE gene expression on the levels of these peptides. Identification of these compensatory mechanisms may provide new candidate genes for investigation in humans.
Angiotensinogen↗
Influence of brain angiotensin on thermoregulation and hydromineral balance during pregnancy in rats.
During mammalian pregnancy, body temperature decreases and there are changes in fluid and electrolyte balance. Angiotensin signaling mechanisms in the brain have been shown to influence thermoregulation and body fluid balance in the nonpregnant state. We hypothesized that brain angiotensin is also implicated in adjusting these physiological systems in the pregnant rat. We compared core temperature and fluid regulation in three groups of pregnant rats: untreated rats, rats receiving continuous infusion of an AT(1) antagonist candesartan (5 microg.kg(-1).day(-1)) into a lateral cerebral ventricle to block brain AT(1) receptors, and rats receiving vehicle [artificial cerebrospinal fluid (aCSF)] vehicle. Untreated and aCSF-treated rats showed a decrease in colonic temperature (-0.5 and -0.8 degrees C respectively) by day 20 of gestation. However, rats treated with candesartan had increased colonic temperature compared with baseline (+0.9 degrees C), and their temperature was significantly higher on days 7 (P < 0.05), 17 (P < 0.05), and 20 (P < 0.001) compared with the other groups (aCSF and untreated). Daily food and water intakes and body weight were not different between the three groups. Similarly, litter sizes and pup weights were equal in all groups. Finally, the expected decreases in plasma Na(+) and osmolality during pregnancy were equivalent in all groups. This study suggests that brain angiotensin mediates the progressive decrease in body temperature that occurs during pregnancy. However, the changes in fluid balance associated with pregnancy are not dependent on brain angiotensin.
Angiotensins↗
Effect of reduced angiotensin-converting enzyme gene expression and angiotensin-converting enzyme inhibition on angiotensin and bradykinin peptide levels in mice.
There is uncertainty about the contribution of angiotensin-converting enzyme (ACE) to angiotensin II formation, with recent studies suggesting that non-ACE enzymes may be the predominant pathway of angiotensin II formation in kidney, heart, and lung. To investigate the role of ACE in angiotensin II formation, we measured angiotensin I and II levels in blood, kidney, and heart of 2 mouse genetic models (ACE.1 and ACE.4) of reduced somatic ACE gene expression and in blood, kidney, heart, lung, adrenal, and brain of mice administered the ACE inhibitor lisinopril. We also measured the levels of bradykinin (1-9) and its ACE metabolite bradykinin (1-7). Reduced ACE gene expression and ACE inhibition had similar effects on angiotensin and bradykinin peptide levels. Angiotensin II levels were reduced by 70% to 97% in blood, 92% to 99% in kidney, 93% to 99% in heart, 97% in lung, and 85% in adrenal and brain. The marked reductions in angiotensin II/angiotensin I ratio indicated that ACE was responsible for at least 90% of angiotensin I conversion to angiotensin II in blood, kidney, heart, lung, and brain, and at least 77% in adrenal. Blood bradykinin (1-9) levels were increased 6.4-fold to 8.4-fold. Heart bradykinin (1-9) levels were increased in ACE.4 mice and the bradykinin (1-7)/bradykinin (1-9) ratio was reduced in kidney and heart of ACE.4 mice and heart of lisinopril-treated mice. These studies demonstrate that ACE is the predominant pathway of angiotensin II formation in blood and tissues of mice and plays a major role in bradykinin (1-9) metabolism in blood and, to a lesser extent, in kidney and heart.
Adrenal Glands↗
The physiological regulation of thirst and fluid intake.
Thirst is important for maintaining body fluid homeostasis and may arise from deficits in either intracellular or extracellular fluid volume. Neural signals arising from osmotic and hormonal influences on the lamina terminalis may be integrated within the brain, with afferent information relayed from intrathoracic baroreceptors via the hindbrain to generate thirst.
Animals↗
Visualization of functionally activated circuitry in the brain.
We have used a transgenic approach to visualize functionally activated neurons and their projections. The transgenic mice contain a tau-lacZ fusion gene regulated by the promoter for c-fos, an immediate early gene that is rapidly induced in neurons after functional stimulation. Constitutive expression of beta-galactosidase (beta-gal), the lacZ product, was low and in accord with previous reports of c-fos expression. However, expression of beta-gal in positive neurons was clearly in cell bodies, axons, and dendrites. Treatment of the mice with kainic acid, a strong inducer of c-fos expression, resulted in high induction of beta-gal. beta-gal was induced in the same defined populations of neurons in the brain as those that express c-fos after kainic acid induction. Furthermore, the pattern of beta-gal expression within the neurons changed over time after kainic acid treatment. Early after kainate treatment, beta-gal was found mainly in cell bodies; at later times, expression extended further along the neuronal processes. This expression pattern is consistent with induction and anterograde transport of the Fos-Tau-beta-gal protein in the neurons. To test whether a functionally activated pathway could be visualized, transgenic mice were deprived of water, which activates nuclei involved in body fluid homeostasis. beta-gal induction was traced in neurons and their processes in the lamina terminalis, in magnocellular neurons of the supraoptic and paraventricular nuclei, and in their projections to the posterior pituitary gland. This strategy allowed the mapping of an activated osmoregulatory pathway. This transgenic approach may have general application in the mapping of functionally activated circuitry in the brain.
Animals↗
Aldosterone acts on the kidney, not the brain, to cause mineralocorticoid hypertension in sheep.
OBJECTIVE: To determine the extent to which mineralocortioid hypertension depends on a direct action of aldosterone on the kidney or on the brain. METHODS: Studies were performed in conscious sheep that were previously uninephrectomized, implanted with silastic cannulae in the renal artery of the remaining kidney, and had guide tubes implanted over the lateral cerebral ventricles. The effect of aldosterone, infused either intrarenally (i.r.; 2 microg/h) or intravenously (i.v.; 2 and 10 microg/h) for 10 days (n = 5), on arterial pressure and fluid and electrolyte balance was determined. The i.r. (2 microg/h) and i.v. (10 microg/h) doses were calculated to give similar intrarenal concentrations of aldosterone. In a further study, the effect of intracerebroventricular (i.c.v.) infusion of aldosterone (2 microg/h for 21 days) on arterial pressure was examined (n = 5). RESULTS: Infusion of aldosterone caused a progressive increase in mean arterial pressure from 83 +/- 3 mmHg to a maximum of 100 +/- 4 mmHg (P < 0.001) with 2 microg/h i.r. and from 84 +/- 3 mmHg to a maximum of 104 +/- 4 mmHg (P < 0.001) with 10 microg/h i.v., both by day 7. With both infusions there were similar increases in plasma [Na+] and decreases in plasma [K+] and total protein concentration (P < 0.05) between days 3 and 5; these were maintained throughout the infusion. There were no significant changes with i.v. aldosterone (2 microg/h). Long-term i.c.v. infusion of aldosterone (2 microg/h for 21 days) caused no change in arterial pressure. CONCLUSIONS: In conscious sheep the hypertensive response to aldosterone resulted from an action on the kidney, with no evidence for a direct action on the brain.
Aldosterone↗