scholarly journals Physiological roles of A1 and A2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed using knockout mice and caffeine

2009 ◽  
Vol 296 (4) ◽  
pp. H1141-H1149 ◽  
Author(s):  
Jiang-Ning Yang ◽  
Jiang-Fan Chen ◽  
Bertil B. Fredholm

Heart rate (HR), body temperature (Temp), locomotor activity (LA), and oxygen consumption (O2C) were studied in awake mice lacking one or both of the adenosine A1 or A2A receptors (A1R or A2AR, respectively) using telemetry and respirometry, before and after caffeine administration. All parameters were lower during day than night and higher in females than males. When compared with wild-type (WT) littermates, HR was higher in male A1R knockout (A1RKO) mice but lower in A2ARKO mice and intermediate in A1-A2AR double KO mice. A single dose of an unselective β-blocker (timolol; 1 mg/kg) abolished the HR differences between these genotypes. Deletion of A1Rs had little effect on Temp, whereas deletion of A2ARs increased it in females and decreased it in males. A1-A2ARKO mice had lower Temp than WT mice. LA was unaltered in A1RKO mice and lower in A2ARKO and A1-A2ARKO mice than in WT mice. Caffeine injection increased LA but only in mice expressing A2AR. Caffeine ingestion also increased LA in an A2AR-dependent manner in male mice. Caffeine ingestion significantly increased O2C in WT mice, but less in the different KO mice. Injection of 30 mg/kg caffeine decreased Temp, especially in KO mice, and hence in a manner unrelated to A1R or A2AR blockade. Selective A2B antagonism had little or no effect. Thus A1R and A2AR influence HR, Temp, LA, and O2C in mice in a sex-dependent manner, indicating effects of endogenous adenosine. The A2AR plays an important role in the modulation of O2C and LA by acute and chronic caffeine administration. There is also evidence for effects of higher doses of caffeine being independent of both A1R and A2AR.

1985 ◽  
Vol 248 (5) ◽  
pp. G532-G538
Author(s):  
M. V. Singer ◽  
W. Niebel ◽  
K. H. Uhde ◽  
D. Hoffmeister ◽  
H. Goebell

In dogs with gastric and pancreatic fistulas, we studied the effect of intravenous atropine in doses ranging from 0.9 to 58 nmol X kg-1 X h-1 on the pancreatic secretory response to secretin before and after truncal vagotomy. Truncal vagotomy did not alter the incremental bicarbonate response to secretin. Before and after truncal vagotomy, 7 nmol X kg-1 X h-1 and all higher doses of atropine sulfate significantly decreased the bicarbonate response to low doses (5.2 and 10.3 pmol X kg-1 X h-1) of secretin but had no significant effect on responses to high doses (20.5 and 41 pmol X kg-1 X h-1). The inhibitory potency of the effective doses of atropine did not differ significantly. Secretin did not stimulate pancreatic protein output above basal. Truncal vagotomy reduced protein output basally and during secretin by about 50%. Before and after truncal vagotomy, 7 nmol X kg-1 X h-1 and all higher doses of atropine significantly decreased protein output basally and during secretin. Secretin and truncal vagotomy did not alter basal heart rate. Only the three highest doses (14, 29, and 58 nmol X kg-1 X h-1) of atropine significantly increased heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)


1962 ◽  
Vol 203 (4) ◽  
pp. 758-761 ◽  
Author(s):  
C. L. Gemmill ◽  
K. M. Browning

A study at 5 C was made of body temperature and heart rate after a standard dose of sodium pentobarbital in normal, thyroidectomized, and hypermetabolic rats before and after subjection to 5 C for 46 hr. It was found that after subjection to cold in the normal rats, the body temperature and heart rate in some animals had more ability to recover after the barbiturate than in rats without previous exposure to cold. There was no ability to recover in the thyroidectomized animals either before or after subjection to cold. Most of the normal and thyroidectomized rats either with or without previous exposure to cold given sodium 3,3',5-l-triiodothyronine (T-3) had recoveries after the barbiturate. Some rats given T-3 and subjected to cold had a primary fall in temperature and heart rate that was followed by recovery and then a secondary fall.


2004 ◽  
Vol 287 (4) ◽  
pp. R749-R758 ◽  
Author(s):  
Annika Åstrand ◽  
Mohammad Bohlooly-Y ◽  
Sara Larsdotter ◽  
Margit Mahlapuu ◽  
Harriet Andersén ◽  
...  

Melanin-concentrating hormone (MCH) plays an important role in energy balance. The current studies were carried out on a new line of mice lacking the rodent MCH receptor (MCHR1−/− mice). These mice confirmed the previously reported lean phenotype characterized by increased energy expenditure and modestly increased caloric intake. Because MCH is expressed in the lateral hypothalamic area, which also has an important role in the regulation of the autonomic nervous system, heart rate and blood pressure were measured by a telemetric method to investigate whether the increased energy expenditure in these mice might be due to altered autonomic nervous system activity. Male MCHR1−/− mice demonstrated a significantly increased heart rate [24-h period: wild type 495 ± 4 vs. MCHR1−/− 561 ± 8 beats/min ( P < 0.001); dark phase: wild type 506 ± 8 vs. MCHR1−/− 582 ± 9 beats/min ( P < 0.001); light phase: wild type 484 ± 13 vs. MCHR1−/− 539 ± 9 beats/min ( P < 0.005)] with no significant difference in mean arterial pressure [wild type 110 ± 0.3 vs. MCHR1−/− 113 ± 0.4 mmHg ( P > 0.05)]. Locomotor activity and core body temperature were higher in the MCHR1−/− mice during the dark phase only and thus temporally dissociated from heart rate differences. On fasting, wild-type animals rapidly downregulated body temperature and heart rate. MCHR1−/− mice displayed a distinct delay in the onset of this downregulation. To investigate the mechanism underlying these differences, autonomic blockade experiments were carried out. Administration of the adrenergic antagonist metoprolol completely reversed the tachycardia seen in MCHR1−/− mice, suggesting an increased sympathetic tone.


2001 ◽  
Vol 280 (5) ◽  
pp. H2255-H2263 ◽  
Author(s):  
Alp Sener ◽  
Francine G. Smith

Experiments were carried out in conscious chronically instrumented lambs aged 1 ( n = 6) and 6 wk ( n = 5) to evaluate the arterial baroreflex control of heart rate (HR) during postnatal maturation and to investigate any modulatory role of endogenously produced nitric oxide (NO). Before and after intravenous administration of 20 mg/kg of the l-arginine analog N G-nitro-l-arginine methyl ester (l-NAME), the arterial baroreflex was assessed by measuring HR responses to increases and decreases in systolic arterial pressure achieved by intravenous administration of phenylephrine and sodium nitroprusside. The HR range over which the baroreflex operates and minimum HR as well as maximum gain were greater at 1 than at 6 wk of age. These age differences were abolished in the presence ofl-NAME, which decreased the HR range and gain of the arterial baroreflex control of HR at 1 but not at 6 wk of age. These data provide new information that age-dependent effects of the arterial baroreflex appear to result from effects of endogenously produced NO.


2019 ◽  
Vol 26 (12) ◽  
pp. 2070-2074
Author(s):  
Muhammad Jahangir Mujahid ◽  
Sobia Khalid ◽  
Shehla Mujahid ◽  
Muhammad Riaz ◽  
Khurram Malik ◽  
...  

Carvedilol is a β-blocker (non-selective). It causes vasoconstriction in the splanchnic vessels and causes reduction of portal inflow. Hence this change causes less destruction of platelets in the patients having splenomegaly with portal hypertension and cirrhosis. Objectives: The objective of the study is to find out the effect of carvedilol on thrombocytopenia in cirrhotic patients of hepatitis C. Study Design: Descriptive study. Settings: Department of Gastroenterology, Fatima Memorial Hospital, Lahore. Period: Six months from 17th October 2015 to 16th April 2016. Material & Method: Data was collected using designed proformas. All patients with hepatitis C having cirrhosis of liver, splenomegaly and a platelet count of less than 100,000/mm3 were included after taking informed consent. Dose of carvedilol was managed so that 25% reduction in heart rate was achieved. Platelet count was repeated after two weeks. Blood pressure, pulse and platelet count before and after 25% reduction in heart rate with carvedilol was compared. Changes in platelet count, blood pressure, pulse and dose of carvedilol were also calculated. <0.05 p value was taken as significant. Results: A total of 66% patients responded to carvedilol therapy and showedmean rise in platelet count of 16 ± 10.3. (P-Value <0.05). Changes in platelet count with change in blood pressure, pulse and with dose of carvedilol were found to be significant. (P<0.05). Conclusion: Carvedilol causes improvement in thrombocytopenia in cirrhotic patients.


1995 ◽  
Vol 89 (5) ◽  
pp. 475-480 ◽  
Author(s):  
Kwasi Debrah ◽  
Rob Haigh ◽  
Robert Sherwin ◽  
June Murphy ◽  
David Kerr

1. The effects of acute and chronic caffeine ingestion on supine- and tilt- (60 min at 70°) induced changes in middle cerebral artery velocity (Vmca), heart rate, blood pressure and counter-regulatory hormone levels (catecholamines, growth hormone and cortisol) were studied in nine healthy volunteers. A double-blind, placebo-controlled design was used to study acute effects followed by an open study after 6 days of chronic caffeine use. 2. In the supine position, acute ingestion of caffeine (250 mg) was associated with a fall in Vmca [−11 cm/s, point estimate of difference versus placebo (95% confidence interval: −17, −6) cm/s, P < 0.001] and a rise in mean arterial pressure [+4 (1, 6) mmHg, P < 0.01] and plasma adrenaline levels [+138 (53, 223) pmol/l, P < 0.01]. After chronic caffeine use, the pressor and adrenaline responses, but not the drop in Vmca, were significantly attenuated. 3. On tilting to 70° the fall in Vmca was greater with placebo than after acute caffeine ingestion [−10 (−14, −15) cm/s, P < 0.01], whereas increments (above supine values) in heart rate, mean arterial pressure and hormone levels were unchanged by caffeine. In contrast, the adrenaline [+126 (29, 282) pmol/l, P < 0.01] and noradrenaline [+ 0.6 (0.1, 0.9) nmol/l, P < 0.05] responses to tilting were augmented after acute caffeine ingestion. Chronic caffeine supplementation did not alter the fall in Vmca associated with tilting, but significantly attenuated the adrenaline response (P < 0.01 compared with the acute study). 4. Acute caffeine ingestion and orthostasis are both associated with a reduction in Vmca and a rise in mean arterial pressure and adrenaline levels. The acute effects of caffeine on mean arterial pressure and adrenaline but not on Vmca are lost with sustained caffeine intake. These results suggest dissociation between the development of central and peripheral tolerance after chronic caffeine use.


2017 ◽  
Vol 1 (06) ◽  
pp. E212-E219
Author(s):  
Kimberly Bjugstad ◽  
Paul Gutowski ◽  
Jennifer Pekarek ◽  
Pamela Bourg ◽  
Charles Mains ◽  
...  

AbstractDespite the unique opportunity race car driving provides to study exercise in extreme conditions, the sport of racing is under-represented. A better understanding of how racing changes physiological measures combined with driver demographics may help reduce driver risks and expand the field of driver science. This study charted the changes in heart rate, body temperature, blood pressure, static oxidation reduction potential (sORP), and antioxidant capacity in drivers before and after racing (n=23). The interaction between racing and driver characteristics on physiological variables were evaluated. Heart rate, body temperature, and sORP were elevated after racing (P<0.05). Age, cockpit temperature, experience, and speed did not correlate with physiological or oxidative measures (P>0.05). Elevated post-race sORP values were associated with higher pre-race systolic blood pressure and lower antioxidant capacity (P<0.05). We conclude that racing alters the redox response in drivers and that drivers’ pre-race systolic blood pressure and antioxidant capacity can further alter it. A better understanding of the physical and oxidative changes which result from racing may help minimize the unique risks


2021 ◽  
Vol 8 ◽  
Author(s):  
Mahmoud Kandeel ◽  
Adel I. Almubarak ◽  
Jamal Hussen ◽  
Wael El-Deeb ◽  
Katharigatta N. Venugopala

Sedatives and tranquilizers are important in the control of excited camels during camel transport. This study was conducted to investigate the clinical sedation of camels with acepromazine and its correlation with pharmacokinetics and pharmacodynamics. The sedation score, heart rate, respiration, body temperature, and pharmacokinetics were monitored before and after acepromazine injection, and myeloid marker expression was analyzed using membrane immunofluorescence and flow cytometry. The distribution (t1/2α) and elimination (t1/2β) half-lives were 0.1 and 9.4 h, respectively. The volume of distribution at steady state (Vss) was 20.01 L/kg, and the mean residence time (MRT) was 12.25 h. Sedation started rapidly within 10 min followed by persistent low-medium sedation for 2 h with an average sedation score of 1.2 ± 0.61, which might be associated with a slow elimination phase and prolonged MRT. Compared to horses, camels showed a lower clearance rate, higher volume of distribution, and higher elimination half-life. Slight changes in body temperature and heart and respiratory rate, as well as a lower hematocrit and changes in blood cell composition, suggest the careful application of acepromazine in animals with abnormal blood parameters or poor vital conditions.


Author(s):  
M. H. Wheeler ◽  
W. J. Tolmsoff ◽  
A. A. Bell

(+)-Scytalone [3,4-dihydro-3,6,8-trihydroxy-l-(2Hj-naphthalenone] and 1,8-di- hydroxynaphthalene (DHN) have been proposed as intermediates of melanin synthesis in the fungi Verticillium dahliae (1, 2, 3, 4) and Thielaviopsis basicola (4, 5). Scytalone is enzymatically dehydrated by V. dahliae to 1,3,8-trihydroxynaphthalene which is then reduced to (-)-vermelone [(-)-3,4- dihydro-3,8-dihydroxy-1(2H)-naphthalenone]. Vermelone is subsequently dehydrated to DHN which is enzymatically polymerized to melanin.Melanin formation in Curvularia sp., Alternaria sp., and Drechslera soro- kiniana was examined by light and electron-transmission microscopy. Wild-type isolates of each fungus were compared with albino mutants before and after treatment with 1 mM scytalone or 0.1 mM DHN in 50 mM potassium phosphate buffer, pH 7.0. Both chemicals were converted to dark pigments in the walls of hyphae and conidia of the albino mutants. The darkened cells were similar in appearance to corresponding cells of the wild types under the light microscope.


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