scholarly journals Differential control of metabolic and cardiovascular functions by melanocortin-4 receptors in proopiomelanocortin neurons

2013 ◽  
Vol 305 (4) ◽  
pp. R359-R368 ◽  
Author(s):  
Jussara M. do Carmo ◽  
Alexandre A. da Silva ◽  
John S. Rushing ◽  
Benjamin Pace ◽  
John E. Hall

We examined the role of melanocortin-4 receptors (MC4R) in proopiomelanocortin (Pomc) neurons in regulating metabolic and cardiovascular functions. Using Cre-loxP technology, we selectively rescued MC4R in Pomc neurons of mice with whole body MC4R deficiency (MC4R-Pomc-Cre mice). Body weight, food intake, and whole body oxygen consumption (V̇o2) were determined daily, and blood pressure (BP), heart rate (HR), and body temperature were measured 24 h/day by telemetry. An intracerebroventricular cannula was placed in the right lateral ventricle for intracerebroventricular infusions. Littermate MC4R-deficient (LoxTB-MC4R) mice were used as controls. After control measurements, the MC4R antagonist (SHU-9119; 1 nmol/h) was infused intracerebroventricularly for 7 days. Compared with LoxTB-MC4R mice, MC4R-Pomc-Cre mice were less obese (47 ± 2 vs. 52 ± 2 g) and had increased energy expenditure (2,174 ± 98 vs. 1,990 ± 68 ml·kg−1·min−1), but food intake (4.4 ± 0.2 vs. 4.3 ± 0.3 g/day), BP (112 ± 1 vs. 109 ± 3 mmHg), and HR [557 ± 9 vs. 551 ± 14 beats per minute (bpm)] were similar between groups. Chronic SHU-9119 infusion increased food intake (4.2 ± 0.2 to 6.1 ± 0.5 g/day) and body weight (47 ± 2 to 52 ± 2 g) in MC4R-Pomc-Cre mice, while no changes were observed in LoxTB-MC4R mice. Chronic SHU-9119 infusion also increased BP and HR by 5 ± 1 mmHg and 60 ± 8 bpm in MC4R-Pomc-Cre mice without altering BP or HR in LoxTB-MC4R mice. These results indicate that MC4Rs in Pomc neurons are important for regulation of energy balance. In contrast, while activation of MC4R in Pomc neurons facilitates the BP response to acute stress, our data do not support a major role of MC4R in Pomc neurons in regulating baseline BP and HR.

2018 ◽  
Vol 120 (2) ◽  
pp. 633-643 ◽  
Author(s):  
Chris L. Schaich ◽  
Theresa L. Wellman ◽  
Zachary Einwag ◽  
Richard A. Dutko ◽  
Benedek Erdos

Brain-derived neurotrophic factor (BDNF) expression increases in the paraventricular nucleus of the hypothalamus (PVN) during stress, and our recent studies indicate that BDNF induces sympathoexcitatory and hypertensive responses when injected acutely or overexpressed chronically in the PVN. However, it remained to be investigated whether BDNF is involved in the mediation of stress-induced cardiovascular responses. Here we tested the hypothesis that inhibition of the high-affinity BDNF receptor TrkB in the PVN diminishes acute stress-induced cardiovascular responses. Male Sprague-Dawley rats were equipped with radiotelemetric transmitters for blood pressure measurement. BDNF-TrkB signaling was selectively inhibited by viral vector-mediated bilateral PVN overexpression of a dominant-negative truncated TrkB receptor (TrkB.T1, n = 7), while control animals ( n = 7) received green fluorescent protein (GFP)-expressing vector injections. Rats were subjected to acute water and restraint stress 3–4 wk after vector injections. We found that body weight, food intake, baseline mean arterial pressure (MAP), and heart rate were unaffected by TrkB.T1 overexpression. However, peak MAP increases were significantly reduced in the TrkB.T1 group compared with GFP both during water stress (GFP: 39 ± 2 mmHg, TrkB.T1: 27 ± 4 mmHg; P < 0.05) and restraint stress (GFP: 41 ± 3 mmHg, TrkB.T1: 34 ± 2 mmHg; P < 0.05). Average MAP elevations during the poststress period were also significantly reduced after both water and restraint stress in the TrkB.T1 group compared with GFP. In contrast, heart rate elevations to both stressors remained unaffected by TrkB.T1 overexpression. Our results demonstrate that activation of BDNF high-affinity TrkB receptors within the PVN is a major contributor to acute stress-induced blood pressure elevations. NEW & NOTEWORTHY We have shown that inhibition of the high-affinity brain-derived neurotrophic factor receptor TrkB in the paraventricular nucleus of the hypothalamus significantly reduces blood pressure elevations to acute stress without having a significant impact on resting blood pressure, body weight, and food intake.


1993 ◽  
Vol 264 (1) ◽  
pp. E11-E17 ◽  
Author(s):  
E. E. Blaak ◽  
M. A. van Baak ◽  
K. P. Kempen ◽  
W. H. Saris

This study was intended to investigate the role of alpha- and beta-adrenoceptor populations in the sympathetically mediated thermogenesis in healthy lean males. In the first study, the beta 1-, beta 2-, and beta 3-agonist isoprenaline was infused in increasing doses with and without simultaneous infusion of the beta 1-blocker atenolol (Iso and Iso+AT, respectively). There was an increase in whole body energy expenditure (EE) after infusing Iso+AT (P < 0.001) and an almost twofold higher increase after infusion of Iso only (P < 0.001). Stimulation of the beta 2-adrenoceptors by a specific agonist (salbutamol) resulted in a significant increase in EE (P < 0.001). The effect of stimulation of alpha 1-adrenoceptors on EE was measured by infusing increasing doses of the alpha 1-agonist phenylephrine. EE did not change, whereas blood pressure (BP) increased (P < 0.001) and heart rate decreased (P < 0.01). In addition to this study, the alpha 1-, alpha 2-, beta 1-, beta 2-, and beta 3-agonists norepinephrine and epinephrine were infused with simultaneous infusion of the beta 1- and beta 2-blocker propranolol. In both studies, there was no effect on EE, whereas BP increased (P < 0.01). In conclusion, in healthy male lean volunteers both beta 1- and beta 2-adrenoceptors are involved in the sympathetically mediated thermogenesis, whereas the alpha 1-, alpha 2-, and beta 3-adrenoceptors do not play a role.


1998 ◽  
Vol 201 (15) ◽  
pp. 2235-2242 ◽  
Author(s):  
J Altimiras ◽  
C E Franklin ◽  
M Axelsson

The cardiac limb of the baroreflex loop was studied in the saltwater crocodile Crocodylus porosus. The classical pharmacological methodology using phenylephrine and sodium nitroprusside was used to trigger blood pressure changes, and the resulting alterations in heart rate were analysed quantitatively using a logistic function. Interindividual differences in resting heart rates and blood pressures were observed, but all seven animals displayed clear baroreflex responses. Atropine and sotalol greatly attenuated the response. A maximal baroreflex gain of 7.2 beats min-1 kPa-1 was found at a mean aortic pressure of 6.1 kPa, indicating the active role of the baroreflex in a wide pressure range encompassing hypotensive and hypertensive states. At the lowest mean aortic pressures (5.0 kPa), the synergistic role of the pulmonary-to-systemic shunt in buffering the blood pressure drop also contributes to blood pressure regulation. Pulse pressure showed a better correlation with heart rate and also a higher gain than mean aortic, systolic or diastolic pressures, and this is taken as an indicator of the existence of a differential control element working simultaneously with a linear proportional element.


2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Joanna Witkoś ◽  
Magdalena Hartman-Petrycka

Introduction: Medical science is constantly looking for effective methods to prevent involutional changes. Whole-body vibration training is a promising form of systemic rehabilitation. Aim: The aim of the study was to assess the effect of whole-body vibration on basic cardiovascular parameters (heart rate and blood pressure) and changes in the perception of an external stimulus in postmenopausal women with different body composition. Material and methods: The study was pilot and involved 20 women. Before the procedure, the body composition analysis was performed using the Tanita analyser. All participants underwent a series of vibration massage treatments lasting 30 minutes. Blood pressure, heart rate and sensory threshold levels were measured before and after the vibrotherapy. Results: Diastolic blood pressure before vs. after (median; 74.20 vs. 71.45 mmHg; p=0.047), heart rate before vs. after (median; 67.40 vs. 66.00 bpm; p<0.001). Higher water content positively correlated with a decrease in diastolic blood pressure (R=0.51; p<0.05). The older the woman was, the less the heart rate decreased (R=-0.45; p<0.05). After vibrotherapy, the sensory threshold values in the non-dominant hand decreased slightly (p=0.076). The greater the visceral fat content (R=-0.48; p<0.05) and body weight (R=-0.56; p<0.05), the smaller was the improvement in the threshold. Conclusions: After whole-body vibration, the values of diastolic blood pressure and heart rate in the examined women were lower than those recorded before the procedure. It has been shown that the higher water content in the female body was associated with a greater reduction in diastolic blood pressure. However, the older the woman, the less was the decrease in heart rate. After the whole-body vibrotherapy, only a slight decrease in the sensory threshold was noted. However, it was found that in the studied women the greater the content of visceral fat tissue and the body weight, the smaller the change in sensory sensitivity.


Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Zhen Wang ◽  
Jussara M do Carmo ◽  
Alexandre A da Silva ◽  
John E Hall

Suppressor of cytokine signaling 3 (SOCS3), a negative regulator of leptin signaling, may be involved in development of obesity-induced leptin resistance. Although we previously showed that activation of proopiomelanocortin (POMC) neurons mediates the chronic effects of leptin on blood pressure (BP), the role of SOCS3 in modulating BP in obesity is still unclear. In this study, we investigated the role of SOCS3 specifically in POMC neurons in regulating body weight, glucose handling and BP in mice fed a normal or high fat (45%, HFD) chow. Male and female SOCS3flox/flox-POMC/cre mice in which SOCS3 was selectively deleted in POMC neurons and control SOCS3flox/flox mice were used. Food intake and body weight were measured from 8 to 16 weeks of age, and a glucose tolerance test (GTT) was performed at 20 wks of age. At 22 wks of age, mice were implanted with telemetry probe to measure BP and heart rate (HR) and fed a HFD for 6 weeks. Compared to control mice, both male and female SOCS3flox/flox-POMC/cre mice were lighter at 16 wks (29.1 ± 3.5 vs 31.9 ± 3.6 g in male and 21.5 ± 2.2 vs 26.1 ± 5.7 in female, n=9-11, p<0.05) but food intake was similar in both groups. Only male SOCS3flox/flox-POMC/cre mice exhibited improved glucose handling (AUC: 1059 ± 52 vs 1283 ± 54 mg/dL x 120 min, n=7-10, p<0.05 ) and no differences were observed in female mice. When fed normal chow, BP was similar in SOCS3flox/flox-POMC/cre and control mice (116 ± 7 vs 113 ± 5 mmHg) at 23 wks. After a HFD for 6 weeks, SOCS3flox/flox-POMC/cre mice had a greater BP increase compared to control mice (7.2 ± 1.9 vs 0.9 ± 1.8 mmHg, n=4-9, P<0.05) but no significant differences were observed in food intake or body weight between two groups. These results suggest that SOCS3 deletion specifically in POMC neurons reduced body weight in male and female mice, and improved glucose handling only in male mice. HFD increased BP in SOCS3flox/flox-POMC/cre but not in control mice, suggesting that SOCS3 in POMC neurons may modulate BP response to HFD.


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Rodrigo O Maranon ◽  
Jussara do Carmo ◽  
Roberta Lima ◽  
Jane F Reckelhoff

The mechanisms responsible for hypertension in postmenopausal women have not been completely elucidated. We have shown previously that MAP in old female SHR is mediated in part by sympathetic activation. In male SHR leptin causes sympathetic activation via the melanocortin 3 / 4 receptor (MC3/4R) activation, and MC3/4R blockade reduces their blood pressure. The hypothesis of the present study was that MC3/4R also contributes to hypertension in old female SHR. Female SHR (aged 18 mos, n=6) received MC3/4 receptor antagonist SHU-9119 (1 nmol/h via minipump) or saline vehicle (n=5 controls). After two weeks recovery, MAP and heart rate (HR) were measured for 5 days during baseline period, and then rats received SHU 9119 or saline icv, and MAP and HR were recorded for 7 days. MC3/4R antagonism produced an increase in food intake (17.1±2 gr, n=5, vs 26.6±1 gr, n=6, p<0.001) and body weight (217±11 gr,n=5 vs 256±6 gr, n=6; p<0.001), compared to saline controls. However, MC3/4R antagonism had no effect on MAP (baseline period: 174±10 mmHg ,n=4 vs 181±5 mmHg, n=6; p:NS; treatment period, 175±13 mmHg, n=4 vs 172±10 mmHg, n=6; p:NS) or HR (Baseline period: 344±4 bpm, n=4 vs 357±12 bpm, n=6; Treatment period, V-R:345±9 bpm, n=4 vs 332±9 bpm, n=6; p:NS). These results show that MC3/4R plays no role in sympathetic activation and regulation of BP in old female SHR. These data suggest that aging women may need different antihypertensive medications than do men. Supported by NIH HL69192, HL55901; HL66072.


Author(s):  
Rubina Yasmin ◽  
AKM Akhtaruzzaman ◽  
Paresh Chandra Sarker ◽  
Neaz Ahmed ◽  
Ranadhir Kumar Kundu ◽  
...  

This prospective clinical study was carried out in the Dept. of Anaesthesia, Analgesia and Intensive Care Medicine, BSMMU, Dhaka, during the period of May 2003 to July 2003. The study was done to emphasize the importance of giving analgesics preemptively instead of waiting for the child to complain of pain and to produce smooth recovery after surgery by decreasing immediate postoperative pain in children by a simple, safe acceptable drug. The children scheduled for tonsillectomy under general anaesthesia were recruited in this study. The analgesic efficiency of rectal paracetamol in two doses, 25 mg/kg bodywt.(Gr-P25) and 50 mg/kg. bodywt. (Gr-P50) were compared with Diclofenac Sodium suppository 1mg/ kg body weight (Gr-D) given half an hour before induction of anaesthesia. Pain scoring was done by TPPPS (Toddler Pre-schooler postoperative pain scale). Heart rate and blood pressure were stable in Gr-P50 and Gr-D. Time of first demand of analgesic was delayed in Gr-P50 and Gr-D. Total paracetamol consumption in 24 hours was less in Gr-P50(181±14.25) and Gr-D (212±25) than Gr-P25(318± 26.39). Total duration of analgesia in Gr- P50 (657±9.94) mins. and in Gr- D(502±10.63) mins. and in Gr-P25(288±23.17) mins. Pre-emptive high dose rectal paracetamol appears to be more effective than diclofenac sodium suppository for postoperative analgesia in children undergoing tonsillectomy. Journal of BSA, Vol. 18, No. 1 & 2, 2005 p.9-16


2012 ◽  
Vol 47 (2) ◽  
pp. 184-190 ◽  
Author(s):  
Masaki Iguchi ◽  
Andrew E. Littmann ◽  
Shuo-Hsiu Chang ◽  
Lydia A. Wester ◽  
Jane S. Knipper ◽  
...  

Context: Conditions such as osteoarthritis, obesity, and spinal cord injury limit the ability of patients to exercise, preventing them from experiencing many well-documented physiologic stressors. Recent evidence indicates that some of these stressors might derive from exercise-induced body temperature increases. Objective: To determine whether whole-body heat stress without exercise triggers cardiovascular, hormonal, and extra-cellular protein responses of exercise. Design: Randomized controlled trial. Setting: University research laboratory. Patients or Other Participants: Twenty-five young, healthy adults (13 men, 12 women; age = 22.1 ± 2.4 years, height = 175.2 ± 11.6 cm, mass = 69.4 ± 14.8 kg, body mass index = 22.6 ± 4.0) volunteered. Intervention(s): Participants sat in a heat stress chamber with heat (73°C) and without heat (26°C) stress for 30 minutes on separate days. We obtained blood samples from a subset of 13 participants (7 men, 6 women) before and after exposure to heat stress. Main Outcome Measure(s): Extracellular heat shock protein (HSP72) and catecholamine plasma concentration, heart rate, blood pressure, and heat perception. Results: After 30 minutes of heat stress, body temperature measured via rectal sensor increased by 0.8°C. Heart rate increased linearly to 131.4 ± 22.4 beats per minute (F6,24 = 186, P &lt; .001) and systolic and diastolic blood pressure decreased by 16 mm Hg (F6,24 = 10.1, P &lt; .001) and 5 mm Hg (F6,24 = 5.4, P &lt; .001), respectively. Norepinephrine (F1,12 = 12.1, P = .004) and prolactin (F1,12 = 30.2, P &lt; .001) increased in the plasma (58% and 285%, respectively) (P &lt; .05). The HSP72 (F1,12 = 44.7, P &lt; .001) level increased with heat stress by 48.7% ± 53.9%. No cardiovascular or blood variables showed changes during the control trials (quiet sitting in the heat chamber with no heat stress), resulting in differences between heat and control trials. Conclusions: We found that whole-body heat stress triggers some of the physiologic responses observed with exercise. Future studies are necessary to investigate whether carefully prescribed heat stress constitutes a method to augment or supplement exercise.


1980 ◽  
Vol 59 (s6) ◽  
pp. 235s-237s ◽  
Author(s):  
R. W. Rockhold ◽  
J. T. Crofton ◽  
L. Share

1. The cardiovascular effects of an enkephalin analogue were examined in spontaneously hypertensive and normotensive Wistar-Kyoto rats. (D-Ala2)-methionine enkephalin caused a biphasic increase in blood pressure and an increase in heart rate after intracerebroventricular injection. 2. The initial pressor response to (D-Ala2)-methionine enkephalin was greater in hypertensive than in normotensive rats. No difference was noted between groups during the secondary pressor response. Heart rate increases paralleled the secondary increase in blood pressure. 3. Naloxone pretreatment abolished the secondary increase in blood pressure and the tachycardia, but did not blunt the initial pressor response in female Wistar-Kyoto rats. 4. Plasma levels of arginine vasopressin were depressed during the plateau phase of the pressor response in hypertensive rats given intracerebroventricular (d-Ala2)-methionine enkephalin. 5. The results suggest that the cardiovascular effects of central enkephalin are not due to vasopressin, but may involve activation of the sympathetic nervous system.


Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Stacy T Sims ◽  
Sandra Tsai ◽  
Marcia L Stefanick

Background: Barriers to physical activity for obese women include overheating, sweating, fatigue, exhaustion, and rapid heart rate. Adipose tissue acts as a thermal insulator, promoting a greater heat load on the nonfat tissues, reducing heat tolerance; exercise causes a rise in body temperature with an inability to dissipate heat contributing to reduced exercise tolerance. With difficulties of thermoregulation in the sedentary obese population, the aspect of attenuating the discomfort thus associated may encourage continuation of exercise. A heat sink applied to palmar surfaces extracts heat and cools the venous blood, reducing thermal strain by enhancing the volume of cooled venous return. We hypothesized that palmar cooling using a rapid thermal exchange device (RTX) during exercise would attenuate the thermal discomfort of exercise of sedentary obese women, improving exercise tolerance. Methods: To examine whether palmar cooling would impact exercise tolerance in obese women, 24 healthy women aged 30–45 years, with no history of long term structured exercise, a body mass of 120–135% above ideal and/or BMI between 30 and 34.9 were recruited. Women were randomized into a cooling (RXT with 16°C water circulating) or a control (RTX with 37°C water circulating) group and attended 3 exercise sessions a week for 3-months (12 weeks). Each session was comprised of 10 min body weight exercises, 25–45 min treadmill walking at 70–85% HRR with the RTX device, and 10 min of core strengthening exercises. The performance marker was a 1.5 mi walk for time; conducted on the first and last days of the intervention. Mixed models were used to model each of the outcomes as a function of thermal strain, time and treatment with covariates of speed, heart rate, distance, and the interaction of the main effects included in the model. Results: Groups were matched at baseline for key variables (time for 1.5 mile walk test, resting and exercising heart rate [HR], blood pressure [BP], waist circumference [WC], body weight, body mass index [BMI]). Among the cooling group, time to complete the 1.5mile walk test was significantly faster (31.6 ± 2.3 vs. 24.6 ± 2.5 min, pre vs. post, P< 0.01). A greater average exercising HR was observed (136 vs. 154 bpm, pre vs. post, P <0.001), with a significant reduction in WC (41.8 ± 3.1 vs. 39.1 ± 2.2 inches, pre vs. post, P< 0.01) and resting BP (139/84 ± 124/70 mmHg, pre vs. post, P < 0.025). There were no significant differences observed in the control group. Conclusion: Results indicate that exercise tolerance in obese women improved with cooling during exercise, more so than those women who did not have cooling. An improvement in blood pressure, heart rate, waist circumference, and overall aerobic fitness was observed. These findings suggest that by reducing thermal discomfort during exercise, tolerance increases, thus improving cardiovascular parameters of obese women.


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