scholarly journals Diurnal Amplitudes of Arterial Pressure and Heart Rate Are Dampened in Clock Mutant Mice and Adrenalectomized Mice

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3576-3580 ◽  
Author(s):  
Hiroyoshi Sei ◽  
Katsutaka Oishi ◽  
Sachiko Chikahisa ◽  
Kazuyoshi Kitaoka ◽  
Eiji Takeda ◽  
...  
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Clock Gene ◽  
Clock Genes ◽  
Plasma Aldosterone ◽  
Mutant Mice ◽  
Wild Type ◽  
Clock Mutant ◽  
Wild Type Control

Arterial pressure (AP), heart rate (HR), and cardiovascular diseases, including ischemic heart attack and cerebrovascular accident, show diurnal variation. Evidence that circadian-related genes contribute to cardiovascular control has been accumulated. In this study, we measured the AP and HR of Clock mutant mice on the Jcl/ICR background to determine the role of the Clock gene in cardiovascular function. Mice with mutated Clock genes had a dampened diurnal rhythm of AP and HR, compared with wild-type control mice, and this difference disappeared after adrenalectomy. The diurnal acrophase in both mean arterial pressure and HR was delayed significantly in Clock mutant mice, compared with wild-type mice, and this difference remained after adrenalectomy. Clock mutant mice had a lower concentration of plasma aldosterone, compared with wild-type mice. Our data suggest that the adrenal gland is involved in the diurnal amplitude, but not the acrophase, of AP and HR, and that the function of the Clock gene may be related to the nondipping type of AP elevation.

scholarly journals The clock gene Period1 regulates innate routine behaviour in mice

2014 ◽  
Vol 281 (1781) ◽  
pp. 20140034 ◽  
Author(s):  
Philipp Bechstein ◽  
Nils-Jörn Rehbach ◽  
Gowzekan Yuhasingham ◽  
Christoph Schürmann ◽  
Melanie Göpfert ◽  
...  
Keyword(s):  
Clock Gene ◽  
Memory Deficits ◽  
Nest Building ◽  
Partner Choice ◽  
Mutant Mice ◽  
Spatial Learning And Memory ◽  
Wild Type ◽  
Circadian Clock Gene ◽  
Deficient Mice

Laboratory mice are well capable of performing innate routine behaviour programmes necessary for courtship, nest-building and exploratory activities although housed for decades in animal facilities. We found that in mice inactivation of the clock gene Period1 profoundly changes innate routine behaviour programmes like those necessary for courtship, nest building, exploration and learning. These results in wild-type and Period1 mutant mice, together with earlier findings on courtship behaviour in wild-type and period -mutant Drosophila melanogaster , suggest a conserved role of Period- genes on innate routine behaviour. Additionally, both per -mutant flies and Period1 -mutant mice display spatial learning and memory deficits. The profound influence of Period1 on routine behaviour programmes in mice, including female partner choice, may be independent of its function as a circadian clock gene, since Period1 -deficient mice display normal circadian behaviour.

Clockmutation facilitates accumulation of cholesterol in the liver of mice fed a cholesterol and/or cholic acid diet

2008 ◽  
Vol 294 (1) ◽  
pp. E120-E130 ◽  
Author(s):  
Takashi Kudo ◽  
Mihoko Kawashima ◽  
Toru Tamagawa ◽  
Shigenobu Shibata
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Cholic Acid ◽  
Mouse Liver ◽  
Clock Genes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Mutant Mice ◽  
Wild Type ◽  
Clock Mutant

Cholesterol (CH) homeostasis in the liver is regulated by enzymes of CH synthesis such as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and catabolic enzymes such as cytochrome P-450, family 7, subfamily A, and polypeptide 1 (CYP7A1). Since a circadian clock controls the gene expression of these enzymes, these genes exhibit circadian rhythm in the liver. In this study, we examined the relationship between a diet containing CH and/or cholic acid (CA) and the circadian regulation of Hmgcr, low-density lipoprotein receptor ( Ldlr), and Cyp7a1 gene expression in the mouse liver. A 4-wk CA diet lowered and eventually abolished the circadian expression of these genes. Not only clock genes such as period homolog 2 (Drosophila) ( Per2) and brain and muscle arnt-like protein-1 ( Bmal1) but also clock-controlled genes such as Hmgcr, Ldlr, and Cyp7a1 showed a reduced and arrhythmic expression pattern in the liver of Clock mutant mice. The reduced gene expression of Cyp7a1 in mice fed a diet containing CA or CH + CA was remarkable in the liver of Clock mutants compared with wild-type mice, and high liver CH accumulation was apparent in Clock mutant mice. In contrast, a CH diet without CA only elevated Cyp7a1 expression in both wild-type and Clock mutant mice. The present findings indicate that normal circadian clock function is important for the regulation of CH homeostasis in the mouse liver, especially in conjunction with a diet containing high CH and CA.

Comparative actions of adrenomedullin and nitroprusside: interactions with ANG II and norepinephrine

2001 ◽  
Vol 281 (6) ◽  
pp. R1887-R1894 ◽  
Author(s):  
Christopher J. Charles ◽  
M. Gary Nicholls ◽  
Miriam T. Rademaker ◽  
A. Mark Richards
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Peripheral Resistance ◽  
Plasma Renin ◽  
Urine Flow ◽  
Plasma Aldosterone ◽  
Ang Ii ◽  
Biological Responses ◽  
Conscious Sheep

The role of adrenomedullin (ADM) in volume and pressure homeostasis remains undefined. Accordingly, we compared the biological responses to infusions of ADM and nitroprusside (NP; matched for reduction of arterial pressure) and assessed their effects on responses to ANG II and norepinephrine in eight conscious sheep. During matched falls in arterial pressure (8–10 mmHg, both P < 0.001) ADM and NP induced similar increases in heart rate. ADM increased cardiac output ( P < 0.001), and the fall in calculated peripheral resistance was greater with ADM than NP ( P = 0.013). ADM infusions raised plasma ADM levels ( P < 0.001), plasma renin activity ( P = 0.001), and ANG II ( P < 0.001) but tended to blunt any concurrent rise in aldosterone compared with NP ( P = 0.056). ADM maintained both urine flow ( P < 0.001) and sodium excretion ( P = 0.01) compared with falls observed with NP. ADM attenuated the vasopressor actions of exogenous ANG II ( P = 0.006) but not norepinephrine. In addition, ADM antagonized the ANG II-induced rise in plasma aldosterone ( P < 0.001). In conclusion, ADM induces a different spectrum of hemodynamic, renal, and endocrine actions to NP. These results clarify mechanisms by which ADM might contribute to volume and pressure homeostasis.

scholarly journals Natural Zeitgebers Under Temperate Conditions Cannot Compensate for the Loss of a Functional Circadian Clock in Timing of a Vital Behavior in Drosophila

2021 ◽  
pp. 074873042199811
Author(s):  
Franziska Ruf ◽  
Oliver Mitesser ◽  
Simon Tii Mungwa ◽  
Melanie Horn ◽  
Dirk Rieger ◽  
...  
Keyword(s):  
Molecular Clock ◽  
Time Window ◽  
Fruit Fly ◽  
Diel Activity ◽  
Wild Type ◽  
Statistical Measures ◽  
Clock Mutant ◽  
Full Complement ◽  
The Right

The adaptive significance of adjusting behavioral activities to the right time of the day seems obvious. Laboratory studies implicated an important role of circadian clocks in behavioral timing and rhythmicity. Yet, recent studies on clock-mutant animals questioned this importance under more naturalistic settings, as various clock mutants showed nearly normal diel activity rhythms under seminatural zeitgeber conditions. We here report evidence that proper timing of eclosion, a vital behavior of the fruit fly Drosophila melanogaster, requires a functional molecular clock under quasi-natural conditions. In contrast to wild-type flies, period01 mutants with a defective molecular clock showed impaired rhythmicity and gating in a temperate environment even in the presence of a full complement of abiotic zeitgebers. Although period01 mutants still eclosed during a certain time window during the day, this time window was much broader and loosely defined, and rhythmicity was lower or lost as classified by various statistical measures. Moreover, peak eclosion time became more susceptible to variable day-to-day changes of light. In contrast, flies with impaired peptidergic interclock signaling ( Pdf01 and han5304 PDF receptor mutants) eclosed mostly rhythmically with normal gate sizes, similar to wild-type controls. Our results suggest that the presence of natural zeitgebers is not sufficient, and a functional molecular clock is required to induce stable temporal eclosion patterns in flies under temperate conditions with considerable day-to-day variation in light intensity and temperature. Temperate zeitgebers are, however, sufficient to functionally rescue a loss of PDF-mediated clock-internal and -output signaling

scholarly journals Acamprosate-responsive brain sites for suppression of ethanol intake and preference

2011 ◽  
Vol 301 (4) ◽  
pp. R1032-R1043 ◽  
Author(s):  
Allison Brager ◽  
Rebecca A. Prosser ◽  
J. David Glass
Keyword(s):  
Alcohol Intake ◽  
Free Choice ◽  
Clock Gene ◽  
Brain Regions ◽  
Ethanol Intake ◽  
Mutant Mice ◽  
Wild Type ◽  
Circadian Clock Gene ◽  
Recovering Alcoholics ◽  
Brain Reward

Acamprosate suppresses alcohol intake and craving in recovering alcoholics; however, the central sites of its action are unclear. To approach this question, brain regions responsive to acamprosate were mapped using acamprosate microimplants targeted to brain reward and circadian areas implicated in alcohol dependence. mPer2 mutant mice with nonfunctional mPer2, a circadian clock gene that gates endogenous timekeeping, were included, owing to their high levels of ethanol intake and preference. Male wild-type (WT) and mPer2 mutant mice received free-choice (15%) ethanol/water for 3 wk. The ethanol was withdrawn for 3 wk and then reintroduced to facilitate relapse. Four days before ethanol reintroduction, mice received bilateral blank or acamprosate-containing microimplants releasing ∼50 ng/day into reward [ventral tegmental (VTA), peduculopontine tegmentum (PPT), and nucleus accumbens (NA)] and circadian [intergeniculate leaflet (IGL) and suprachiasmatic nucleus (SCN)] areas. The hippocampus was also targeted. Circadian locomotor activity was measured throughout. Ethanol intake and preference were greater in mPer2 mutants than in wild-type (WT) mice (27 g·kg−1·day−1 vs. 13 g·kg−1·day−1 and 70% vs. 50%, respectively; both, P < 0.05). In WTs, acamprosate in all areas, except hippocampus, suppressed ethanol intake and preference (by 40–60%) during ethanol reintroduction. In mPer2 mutants, acamprosate in the VTA, PPT, and SCN suppressed ethanol intake and preference by 20–30%. These data are evidence that acamprosate's suppression of ethanol intake and preference are manifest through actions within major reward and circadian sites.

Time- and age-dependent effects of serotonin on gasping and autoresuscitation in neonatal mice

2013 ◽  
Vol 114 (12) ◽  
pp. 1668-1676 ◽  
Author(s):  
Jianping Chen ◽  
Jennifer Magnusson ◽  
Gerard Karsenty ◽  
Kevin J. Cummings
Keyword(s):  
Heart Rate ◽  
Tryptophan Hydroxylase ◽  
Single Injection ◽  
Heart Rate Recovery ◽  
Wild Type ◽  
Tryptophan Hydroxylase 2 ◽  
Age Dependent ◽  
Long Time ◽  
Time Required

The role of brain stem serotonin (5-hydroxytryptamine, 5-HT) in autoresuscitation in neonatal life is unclear. We hypothesized that a specific loss of 5-HT would compromise gasping and autoresuscitation mainly in the second postnatal week and that acute restoration of 5-HT would reverse the defects. We exposed postnatal day (P)4–5, P8–9, and P11–12 tryptophan-hydroxylase-2 knockout ( TPH2−/−) and wild-type littermates (WT) to 10 episodes of anoxia (97% N2, 3% CO2), measuring survival, gasp latency, gasp frequency ( fB), and the time required to restore eupnea and heart rate. We also tested P8–9 TPH2−/− mice after restoring 5-HT with a single injection of 5-hydroxytryptophan (5-HTP) 1–2 h before testing or with multiple injections beginning 24 h before testing. At P4–5 and P8–9, but not at P11–12, gasp latency and the recovery of eupnea were delayed ∼2- to 3-fold in TPH2−/− pups compared with WT ( P < 0.001). At all ages, TPH2−/− pups displayed reduced gasp fB (∼20–30%; P < 0.001) and delayed heart rate recovery (∼60%; P = 0.002) compared with WT littermates. TPH2−/− survival was reduced compared with WT ( P < 0.001), especially at P8–9 and P11–12 ( P = 0.004). Whereas 1–2 h of 5-HTP treatment improved the gasp latency and fB of P8–9 TPH2−/− pups, improved cardiorespiratory recovery and survival required 24 h of treatment. Our data suggest that 5-HT operates over a long time span (∼24 h) to improve survival during episodic severe hypoxia. Early in development (P4–9), 5-HT is critical for both respiratory and cardiovascular components of autoresuscitation; later (P11–12), it is critical mainly for cardiovascular components. Nevertheless, the effect of 5-HT deficiency on survival is most striking from P8 to P12.

scholarly journals Identifying the role of group III/IV muscle afferents in the carotid baroreflex control of mean arterial pressure and heart rate during exercise

2018 ◽  
Vol 596 (8) ◽  
pp. 1373-1384 ◽  
Author(s):  
Thomas J. Hureau ◽  
Joshua C. Weavil ◽  
Taylor S. Thurston ◽  
Ryan M. Broxterman ◽  
Ashley D. Nelson ◽  
...  
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Muscle Afferents ◽  
Baroreflex Control ◽  
Group Iii ◽  
Carotid Baroreflex

scholarly journals Acute sympathoexcitatory action of angiotensin II in conscious baroreceptor-denervated rats

2002 ◽  
Vol 283 (2) ◽  
pp. R451-R459 ◽  
Author(s):  
Ling Xu ◽  
Alan F. Sved
Keyword(s):  
Heart Rate ◽  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Sympathetic Nerve Activity ◽  
Baroreceptor Reflex ◽  
Ang Ii ◽  
Nerve Activity ◽  
Induced Hypotension ◽  
Baroreceptor Reflexes

Angiotensin II (ANG II) has complex actions on the cardiovascular system. ANG II may act to increase sympathetic vasomotor outflow, but acutely the sympathoexcitatory actions of exogenous ANG II may be opposed by ANG II-induced increases in arterial pressure (AP), evoking baroreceptor-mediated decreases in sympathetic nerve activity (SNA). To examine this hypothesis, the effect of ANG II infusion on lumbar SNA was measured in unanesthetized chronic sinoaortic-denervated rats. Chronic sinoaortic-denervated rats had no reflex heart rate (HR) responses to pharmacologically evoked increases or decreases in AP. Similarly, in these denervated rats, nitroprusside-induced hypotension had no effect on lumbar SNA; however, phenylephrine-induced increases in AP were still associated with transient decreases in SNA. In control rats, infusion of ANG II (100 ng · kg−1 · min−1 iv) increased AP and decreased HR and SNA. In contrast, ANG II infusion increased lumbar SNA and HR in sinoaortic-denervated rats. In rats that underwent sinoaortic denervation surgery but still had residual baroreceptor reflex-evoked changes in HR, the effect of ANG II on HR and SNA was variable and correlated to the extent of baroreceptor reflex impairment. The present data suggest that pressor concentrations of ANG II in rats act rapidly to increase lumbar SNA and HR, although baroreceptor reflexes normally mask these effects of ANG II. Furthermore, these studies highlight the importance of fully characterizing sinoaortic-denervated rats used in experiments examining the role of baroreceptor reflexes.

scholarly journals The PACAP-Regulated Gene Selenoprotein T Is Abundantly Expressed in Mouse and Human β-Cells and Its Targeted Inactivation Impairs Glucose Tolerance

Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3796-3806 ◽  
Author(s):  
Gaëtan Prevost ◽  
Arnaud Arabo ◽  
Long Jian ◽  
Eddy Quelennec ◽  
Dorthe Cartier ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Redox Status ◽  
Human Islets ◽  
Mutant Mice ◽  
Wild Type ◽  
Β Cells ◽  
Cellular Processes ◽  
Insulin Promoter ◽  
Selenoprotein T

Selenoproteins are involved in the regulation of redox status, which affects several cellular processes, including cell survival and homeostasis. Considerable interest has arisen recently concerning the role of selenoproteins in the regulation of glucose metabolism. Here, we found that selenoprotein T (SelT), a new thioredoxin-like protein of the endoplasmic reticulum, is present at high levels in human and mouse pancreas as revealed by immunofluorescence and quantitative PCR. Confocal immunohistochemistry studies revealed that SelT is mostly confined to insulin- and somatostatin-producing cells in mouse and human islets. To elucidate the role of SelT in β-cells, we generated, using a Cre-Lox strategy, a conditional pancreatic β-cell SelT-knockout C57BL/6J mice (SelT-insKO) in which SelT gene disruption is under the control of the rat insulin promoter Cre gene. Glucose administration revealed that male SelT-insKO mice display impaired glucose tolerance. Although insulin sensitivity was not modified in the mutant mice, the ratio of glucose to insulin was significantly higher in the SelT-insKO mice compared with wild-type littermates, pointing to a deficit in insulin production/secretion in mutant mice. In addition, morphometric analysis showed that islets from SelT-insKO mice were smaller and that their number was significantly increased compared with islets from their wild-type littermates. Finally, we found that SelT is up-regulated by pituitary adenylate cyclase-activating polypeptide (PACAP) in β-pancreatic cells and that SelT could act by facilitating a feed-forward mechanism to potentiate insulin secretion induced by the neuropeptide. Our findings are the first to show that the PACAP-regulated SelT is localized in pancreatic β- and δ-cells and is involved in the control of glucose homeostasis.

Role of vasopressin in blood pressure regulation in conscious water-deprived dogs

1983 ◽  
Vol 244 (1) ◽  
pp. R74-R77 ◽  
Author(s):  
J. Schwartz ◽  
I. A. Reid
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Plasma Renin Activity ◽  
Water Deprivation ◽  
Plasma Renin ◽  
Renin Activity ◽  
Pressure Regulation

The role of vasopressin in the regulation of blood pressure during water deprivation was assessed in conscious dogs with two antagonists of the vasoconstrictor activity of vasopressin. In water-replete dogs, vasopressin blockade caused no significant changes in mean arterial pressure, heart rate, plasma renin activity (PRA), or plasma corticosteroid concentration. In the same dogs following 48-h water deprivation, vasopressin blockade increased heart rate from 85 +/- 6 to 134 +/- 15 beats/min (P less than 0.0001), increased cardiac output from 2.0 +/- 0.1 to 3.1 +/- 0.1 1/min (P less than 0.005), and decreased total peripheral resistance from 46.6 +/- 3.1 to 26.9 +/- 3.1 U (P less than 0.001). Plasma renin activity increased from 12.4 +/- 2.2 to 25.9 +/- 3.4 ng ANG I X ml-1 X 3 h-1 (P less than 0.0001) and plasma corticosteroid concentration increased from 3.2 +/- 0.7 to 4.9 +/- 1.2 micrograms/dl (P less than 0.05). Mean arterial pressure did not change significantly. When the same dogs were again deprived of water and pretreated with the beta-adrenoceptor antagonist propranolol, the heart rate and PRA responses to the antagonists were attenuated and mean arterial pressure decreased from 103 +/- 2 to 91 +/- 3 mmHg (P less than 0.001). These data demonstrate that vasopressin plays an important role in blood pressure regulation during water deprivation in conscious dogs.

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