Stimulation of NPY Y2 receptors by PYY3-36 reveals divergent cardiovascular effects of endogenous NPY in rats on different dietary regimens

2004 ◽  
Vol 286 (1) ◽  
pp. R138-R142 ◽  
Author(s):  
Ulrich Nordheim ◽  
Karl G. Hofbauer
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
High Fat Diet ◽  
Cardiovascular Effects ◽  
Cardiovascular Responses ◽  
Chow Diet ◽  
High Fat ◽  
Standard Chow Diet ◽  
Ad Libitum

In the present experiments the gut hormone peptide YY3-36 (PYY3-36), which inhibits neuropeptide Y (NPY) release, was used as a tool to study the cardiovascular effects of endogenous NPY under different dietary regimens in rats instrumented with a telemetry transmitter. In a first experiment, rats were placed on a standard chow diet ad libitum and in a second experiment on a high-fat diet ad libitum. After 6 wk, PYY3-36 (300 μg/kg) or vehicle was injected intraperitoneally. In a third experiment, PYY3-36 or vehicle was administered after 14 days of 50% restriction of a standard chow diet. In food-restricted rats, PYY3-36 increased mean arterial pressure (7 ± 1 mmHg, mean ± SE, P < 0.001 vs. saline, 1-way repeated-measures ANOVA with Bonferroni t-test) and heart rate (22 ± 4 beats/min, P < 0.001) during 3 h after administration. Conversely, PYY3-36 did not influence mean arterial pressure (0 ± 1 mmHg) and heart rate (-8 ± 5 beats/min) significantly in rats on a high-fat diet. Rats fed standard chow diet ad libitum showed an intermediate response (mean arterial pressure 4 ± 1 mmHg, P < 0.05, and heart rate 5 ± 2 beats/min, not significant). Thus, in our studies, divergent cardiovascular responses to PYY3-36 were observed in rats on different dietary regimens. These findings suggest that the cardiovascular effects of PYY3-36 depend on the hypothalamic NPY release, which is increased after chronic food restriction and decreased during a high-fat diet.

Baroreflex sensitivity in the canine model of obesity-induced hypertension

1990 ◽  
Vol 259 (5) ◽  
pp. R981-R985 ◽  
Author(s):  
K. E. Wehberg ◽  
D. B. West ◽  
C. Kieswetter ◽  
J. P. Granger
Keyword(s):  
Heart Rate ◽  
Body Weight ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Sodium Nitroprusside ◽  
High Fat Diet ◽  
Baroreflex Sensitivity ◽  
Canine Model ◽  
High Fat ◽  
Induced Hypertension

Studies have demonstrated abnormalities in baroreflex function in various models of hypertension. The purpose of this study was to examine baroreflex sensitivity in the canine model of obesity-induced hypertension. Baroreflex sensitivity was determined by the relative changes in heart rate (HR) in response to changes in mean arterial pressure (MAP) induced by sodium nitroprusside (Nitro) and phenylephrine (Pe). Studies were performed in conscious lean dogs (n = 10) and obese dogs fed a high-fat diet for 6 wk (n = 8). Body weight averaged 18.1 +/- 0.3 kg in the lean dogs and 26.5 +/- 0.5 kg in the obese dogs. Associated with the 46% increase in body weight in the obese dog group were significant increases in MAP (120.7 +/- 3.0 vs. 102.8 +/- 1.5 mmHg) and HR (132.7 +/- 8.5 vs. 96.4 +/- 3.3 beats/min). Administration of Nitro (0.5, 1.0, 5.0 micrograms.kg-1.min-1) resulted in comparable reductions in MAP in the lean and obese dogs. The reflex increases in HR were significantly greater in the obese animals only with a dose of 5.0 micrograms.kg-1.min-1 of Nitro (55.5 +/- 7.7 vs. 32.0 +/- 7.5 beats/min). Administration of Pe (0.5, 1.0, 5.0 micrograms.kg-1.min-1) resulted in significantly greater increases in MAP in the obese dogs (17.8 +/- 4.6 vs. 4.9 +/- 2.6, 37.1 +/- 4.4 vs. 19.6 +/- 2.7, and 72.7 +/- 7.5 vs. 51.5 +/- 7.1 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Spinal actions of substance P analogues on cardiovascular responses in the rat: a structure–activity analysis

1987 ◽  
Vol 65 (3) ◽  
pp. 412-418 ◽  
Author(s):  
Réjean Couture ◽  
Alka Gupta ◽  
René Kérouac ◽  
Emanuel Escher ◽  
Domenico Regoli
Keyword(s):  
Heart Rate ◽  
Amino Acid ◽  
Mean Arterial Pressure ◽  
Substance P ◽  
Arterial Pressure ◽  
Cardiovascular Effects ◽  
Cardiovascular Responses ◽  
Hypotensive Effect ◽  
Intrathecal Administration ◽  
Substance P Analogues

Ten substance P (SP) analogues were tested for their effects on mean arterial pressure and heart rate following intrathecal administration in the pentobarbital anaesthetized rat. The 10 analogues are [D-Pro4,D-αNpa7,9,10]SP(4–11) (A-I),(D-αNpa7,9,10]Sp (A-II);[D-Trp7,9,10]SP (A-III),[D-Pro4,D-Npa7,9, Phe11]SP(4–11) (A-IV),D-Pro4, D-βNpa7,D-αNpa9,D-Phe11]SP(4–11) (A-V), [D-Pro4,Lys6,D-Trp7,9,10, Phe11]SP(4–11) (A-VII),[D-Pro4,D-Trp7,9,10,Phe11]SP(4–11) (A-X),[D-Pro4,D-Trp7,9,10, Trp11]SP(4–11) (A-VIII),[D-Trp7,9,10, Trp11]SP (A-IX), and [D-Pro4,D-Phe7,9,10, Phe11]SP(4–11) (A-X). At 6.5 nmol, the analogues containing the amino acid D-Npa (A-I, A-II, A-IV, and A-V) or D-Phe (A-X) in positions 7, 9, or 10 or SP or its C-terminal octapeptide are devoid of the long-lasting cardio- and vaso-depressor effects, which are otherwise seen with analogues containing the amino acid D-Trp (A-III, A-VI, A-VII, A-VIII, and A-IX) in the same positions. Some of the analogues containing D-Npa maintain the initial hypotensive effect seen with SP while the analogue containing D-Phe produces only a small hypertensive response. The 10 analogues when tested at a dose that failed to alter basal mean arterial pressure and heart rate did not block the cardiovascular responses elicited by SP and no cross desensitization was observed between SP and these analogues. It appears that these SP analogues exert cardiovascular effects in the rat spinal cord probably without interacting with SP receptors.

High-fat diet is associated with blunted splanchnic sympathoinhibitory responses to gastric leptin and cholecystokinin: implications for circulatory control

2011 ◽  
Vol 300 (3) ◽  
pp. H961-H967 ◽  
Author(s):  
Jackie M. Y. How ◽  
Barbara C. Fam ◽  
Anthony J. M. Verberne ◽  
Daniela M. Sartor
Keyword(s):  
Arterial Pressure ◽  
High Fat Diet ◽  
Cardiovascular Effects ◽  
Vagal Afferents ◽  
Sprague Dawley ◽  
High Fat ◽  
Lower Plasma ◽  
Lower Tertile ◽  
Circulatory Control ◽  
Plasma Leptin

Gastric leptin and cholecystokinin (CCK) act on vagal afferents to induce cardiovascular effects and reflex inhibition of splanchnic sympathetic nerve discharge (SSND) and may act cooperatively in these responses. We sought to determine whether these effects are altered in animals that developed obesity in response to a medium high-fat diet (MHFD). Male Sprague-Dawley rats were placed on a low-fat diet (LFD; n = 8) or a MHFD ( n = 24) for 13 wk, after which the animals were anesthetized and artificially ventilated. Arterial pressure was monitored and blood was collected for the determination of plasma leptin and CCK. SSND responses to leptin (15 μg/kg) and CCK (2 μg/kg) administered close to the coeliac artery were evaluated. Collectively, MHFD animals had significantly higher plasma leptin but lower plasma CCK levels than LFD rats ( P < 0.05), and this corresponded to attenuated or reversed SSND responses to CCK (LFD, −21 ± 2%; and MHFD, −12 ± 2%; P < 0.05) and leptin (LFD, −6 ± 2%; and MHFD, 4 ± 1%; P < 0.001). Alternatively, animals on the MHFD were stratified into obesity-prone (OP; n = 8) or obesity-resistant (OR; n = 8) groups according to their weight gain falling within the upper or lower tertile, respectively. OP rats had significantly higher resting arterial pressure, adiposity, and plasma leptin but lower plasma CCK compared with LFD rats ( P < 0.05). The SSND responses to CCK or leptin were not significantly different between OP and OR animals. These results demonstrate that a high-fat diet is associated with blunted splanchnic sympathoinhibitory responses to gastric leptin and CCK and may impact on sympathetic vasomotor mechanisms involved in circulatory control.

scholarly journals Health Effects of Alternate Day Fasting Versus Pair-Fed Caloric Restriction in Diet-Induced Obese C57Bl/6J Male Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Chloe G. Henderson ◽  
Damian L. Turner ◽  
Steven J. Swoap
Keyword(s):  
T Cell ◽  
Caloric Restriction ◽  
High Fat Diet ◽  
Chow Diet ◽  
Obese Mice ◽  
High Fat ◽  
Mesenteric Lymph Nodes ◽  
Fasting Period ◽  
Alternate Day Fasting ◽  
Ad Libitum

Alternate day fasting (ADF) induces weight loss and improves various markers of health in rodents and humans. However, it is unclear whether the benefits of ADF are derived from the lower caloric intake of ADF or from the 24-h fasting period. Therefore, this study directly compared selected markers for health – such as glucose control, body weight, liver triglycerides, T cell frequencies, and others – in high-fat (60% calories from fat) diet-induced obese mice subjected to either ADF or caloric restriction (CR). Obese mice were randomly assigned to one of four groups: (1) ADF: remained on the high-fat diet, but fed on alternate days (n = 5), (2) PF: remained on the high-fat diet, but pair-fed to the ADF group (n = 5), (3) LF: moved to a chow ad libitum diet (n = 5; 17% calories from fat), and (4) HF: remained on the high-fat ad libitum diet (n = 5). An additional group of non-obese mice maintained on a chow diet since weaning were used as controls (CON: n = 5). After 10 weeks, ADF, PF, and LF mice ate fewer kcals, had a lower body mass, had smaller epididymal fat pads, improved glucose tolerance, and had a lower hepatic triglyceride content relative to HF mice (p &lt; 0.05), but none reached that of CON mice in these measures. T cell frequencies of the spleen, blood, and mesenteric lymph nodes were reduced in ADF, PF, and HF compared to the CON group. Importantly, there were no significant differences between the ADF and PF groups in any of the measurements made in the current study. These data suggest that ADF, PF, and LF diets each lead to improved markers of health relative to high-fat diet-induced obese mice, and that the caloric restriction associated with ADF is the major factor for the noted improvements.

scholarly journals Imaging Fibrogenesis in a Diet-Induced Model of Nonalcoholic Steatohepatitis (NASH)

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
S. V. Hartimath ◽  
R. Boominathan ◽  
V. Soh ◽  
P. Cheng ◽  
X. Deng ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Liver Fibrosis ◽  
Early Detection ◽  
Pet Imaging ◽  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
Detection Sensitivity ◽  
Chow Diet ◽  
High Fat ◽  
Standard Chow Diet

Purpose. Liver fibrosis is the hallmark of chronic nonalcoholic steatohepatitis (NASH) and is characterised by the excessive deposition of extracellular matrix proteins. Early detection and accurate staging of liver fibrosis is critically important for patient management. One of the earliest pathological markers in NASH is the activation of hepatic stellate cells (HSCs) which may be exploited as a marker of fibrogenesis. Activated HSCs secreting factors such as integrin αvβ3 propagate fibrosis. The purpose of the current study was to assess the utility of the integrin αvβ3 imaging agent [18F]FtRGD for the early detection of fibrosis in a diet-induced model of NASH longitudinally using PET imaging. Procedures. Mice were fed with either standard chow diet (SD), high-fat diet (HFD), or a choline-deficient, L-amino acid-defined high-fat fibrogenic diet (CDAHFD) to mimic the clinical pathology of liver disease and followed longitudinally for 10 weeks to assess the development of liver fibrosis using [18F]FtRGD positron emission tomography (PET) imaging. Standard blood biochemistry, histological measures, and qPCR were used to quantify integrin αvβ3, smooth muscle actin, and collagen types 1 and 6 to assess the extent of NASH pathology and accurately stage liver fibrosis. Results. The CDAHFD fibrogenic diet predictably developed hepatic inflammation and steatosis over the 10 weeks studied with little NASH pathology detected in high fat diet-treated animals. Stage 1 fibrosis was detected early by histology at day 21 and progressed to stage 2 by day 35 and stage 3 by day 56 in mice fed with CDAHFD diet only. Noninvasive imaging with [18F]FtRGD correlated well with integrin αvβ3 and was able to distinguish early mild stage 2 fibrosis in CDAHFD animals compared with standard chow diet-fed animals at day 35. When compared with high fat diet-fed animals, [18F]FtRGD was only able to distinguish later moderate stage 2 fibrosis in CDAHFD animals at day 49. Conclusions. The diet-induced progression of liver fibrosis was confirmed using histology and correlated well with the mRNA of integrin αvβ3 and extracellular matrix protein expression. [18F]FtRGD showed very good correlation between liver uptake and integrin αvβ3 expression and similar detection sensitivity to the current clinical gold standard modalities for staging of liver fibrosis.

Naturally occurring hypertension in New World nonhuman primates: potential role of the perifornical hypothalamus

2007 ◽  
Vol 292 (2) ◽  
pp. R937-R945 ◽  
Author(s):  
Orville A. Smith ◽  
Cliff A. Astley
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
New World ◽  
Critical Role ◽  
Cardiovascular Responses ◽  
Routine Laboratory ◽  
New World Primates ◽  
Naturally Occurring

Hypertension is a prominent underlying factor in the genesis of cardiovascular-related morbidity and mortality. A major impediment to the investigation into the causes of the disease is the paucity of naturally occurring animal models of the disease. There is evidence that some species of New World primates spontaneously become hypertensive. We used chronically implanted pressure transducers to assess normally occurring blood pressure and heart rate levels at rest and during routine laboratory procedures in a group of one of these New World primates ( Aotus sp.). Resting mean arterial pressure ranged from 72 to 130 mmHg. Three animals were judged to have resting mean arterial pressure levels in the hypertensive range (≥110 mmHg). In all of the animals, pressor responses to routine laboratory events were exaggerated (average highest mean pressure during 1 min from any session was 97–196 mmHg). Subsequently, the region of the perifornical/lateral hypothalamus known to produce elevated blood pressure and heart rate responses to electrical stimulation was removed, and the blood pressure responses to the laboratory routines were significantly decreased and, in some cases, eliminated. Control lesions in nearby tissue had no effect on these responses. This region may play a critical role in initiating or exacerbating cardiovascular responses that contribute to the development of essential hypertension.

Neuronal and cardiovascular responses to ANF microinjected into the solitary nucleus

1989 ◽  
Vol 256 (2) ◽  
pp. R577-R582 ◽  
Author(s):  
R. Ermirio ◽  
P. Ruggeri ◽  
C. E. Cogo ◽  
C. Molinari ◽  
F. R. Calaresu
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Unit Activity ◽  
Atrial Natriuretic Factor ◽  
Single Unit ◽  
Cardiovascular Responses ◽  
Firing Frequency ◽  
Neuronal Firing ◽  
Single Unit Activity

The effect on single-unit activity, arterial pressure, and heart rate of a microinjection of atrial natriuretic factor (ANF) into 78 histologically verified sites in the nucleus tractus solitarii (NTS) was investigated in rats. Injections of 50 nl of 10(-7) M ANF excited 34 neurons (44%), mainly localized at the level of the obex, inhibited 15 (19%), and had no effect on the remaining 29 (37%). The increase in firing frequency of the 34 excited neurons was always followed by a decline in mean arterial pressure [MAP, -10.6 +/- 1.8 (SE) mmHg; P less than 0.01] and heart rate [HR, -9.6 +/- 3.1 (SE) beats/min; P less than 0.05]. When injections of ANF caused either no effect or inhibition of single-unit activity, no changes in either MAP or HR were observed. Single units excited by injections of ANF were also excited by activation of arterial baroreceptors and inhibited by baroreceptor unloading. Control injections of an inactive peptide analogue of ANF or of vehicle never produced any effects on neuronal firing frequency or on MAP and HR. Similar results were obtained from animals paralyzed and artificially ventilated. These results support the hypothesis that ANF plays a role in the chemical transmission of baroreceptor information within the NTS.

Maternal responses to long-term hypoxemia in sheep

1989 ◽  
Vol 256 (6) ◽  
pp. R1340-R1347 ◽  
Author(s):  
T. Kitanaka ◽  
R. D. Gilbert ◽  
L. D. Longo
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Blood Volume ◽  
Cardiovascular Responses ◽  
Uterine Blood Flow ◽  
O2 Uptake ◽  
Arterial Po2

To determine the maternal cardiovascular responses to long-term hypoxemia, we studied three groups of animals: 1) pregnant ewes (n = 20) at 110-115 days gestation subjected to hypoxia for up to 28 days; 2) pregnant ewes (n = 4) that served as normoxic controls; and 3) nonpregnant ewes (n = 6) subjected to hypoxemia for up to 28 days. We measured mean arterial pressure, heart rate, uterine blood flow, and uterine vascular resistance continuously for 1 h/day while the ewe was exposed to an inspired O2 fraction of 12-13% for at least 17 days. Arterial PO2, O2 saturation, hemoglobin, arteriovenous O2 difference, and uterine O2 uptake were measured daily while blood volume and erythropoietin concentration were measured weekly. In the pregnant hypoxic group arterial PO2 decreased from a control value of 101.5 +/- 5.1 to 59.2 +/- 5.1 Torr within a few minutes, where it remained throughout the study. The hemoglobin concentration increased from 8.9 +/- 0.5 to 10.0 +/- 0.5 g/dl within 24 h where it remained, whereas erythropoietin concentration increased from 16.6 +/- 2.1 to 39.1 +/- 7.8 mU/ml at 24 h but then returned to near-control levels. Arterial glucose concentration, mean arterial pressure, and cardiac output decreased slightly but insignificantly. In contrast, body weight, heart rate, blood volume, uterine blood flow, uterine O2 flow, uteroplacental O2 uptake, and the concentrations of catecholamines and cortisol remained relatively constant. Thus both pregnant and nonpregnant sheep experience relatively minor cardiovascular and hematologic responses in response to long-term hypoxemia of moderate severity.

Spinal action of neurokinins in the rat: effects on mean arterial pressure, heart rate, and vascular permeability

1987 ◽  
Vol 65 (11) ◽  
pp. 2182-2187 ◽  
Author(s):  
Harout Hasséssian ◽  
Réjean Couture ◽  
Line Jacques
Keyword(s):  
Spinal Cord ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Vascular Permeability ◽  
Cardiovascular Responses ◽  
Intrathecal Administration ◽  
Water Soluble ◽  
Neurokinin A ◽  
Anaesthetized Rats

In urethane-anaesthetized rats, the intrathecal administration of 6.5 nmol of substance P (SP), neurokinin A (NKA), or neurokinin B (NKB) at the T8–T10 level of the spinal cord enhances mean arterial pressure and heart rate. However, in the pentobarbital-anaesthetized rat, while NKB produces no effect on mean arterial pressure, NKA produces a biphasic change and SP, a depressor response. All three neurokinins elicit a tachycardia. The following rank order of potency SP ≥ NKA > NKB is observed in relation to these cardiovascular responses when either one of the two anaesthetics is used. The low cardiovascular activity of NKB cannot be attributed to its hydrophobicity, as the water soluble analogue of NKB, [Arg0] NKB, elicits a response as weak as the native peptide. In pentobarbital-anaesthetized rats, the intrathecal administration of 6.5 nmol of SP, also enhances plasma protein extravasation in cutaneous tissues of the back, the hind paws, and the ears. In this response NKA and NKB are either inactive (skin of hind paws) or less potent than SP (ears and dorsal skin). These findings agree with the hypothesis that in the rat spinal cord, the neurokinin receptor producing changes in mean arterial pressure, heart rate, and vascular permeability is of the NK-1 subtype.

scholarly journals Chronic baroreflex activation restores spontaneous baroreflex control and variability of heart rate in obesity-induced hypertension

2013 ◽  
Vol 305 (7) ◽  
pp. H1080-H1088 ◽  
Author(s):  
Radu Iliescu ◽  
Ionut Tudorancea ◽  
Eric D. Irwin ◽  
Thomas E. Lohmeier
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Arterial Pressure ◽  
Cardiac Arrhythmias ◽  
High Fat Diet ◽  
Renal Denervation ◽  
Gradual Increase ◽  
High Fat ◽  
Baroreflex Control ◽  
Cardiovascular Dynamic

The sensitivity of baroreflex control of heart rate is depressed in subjects with obesity hypertension, which increases the risk for cardiac arrhythmias. The mechanisms are not fully known, and there are no therapies to improve this dysfunction. To determine the cardiovascular dynamic effects of progressive increases in body weight leading to obesity and hypertension in dogs fed a high-fat diet, 24-h continuous recordings of spontaneous fluctuations in blood pressure and heart rate were analyzed in the time and frequency domains. Furthermore, we investigated whether autonomic mechanisms stimulated by chronic baroreflex activation and renal denervation—current therapies in patients with resistant hypertension, who are commonly obese—restore cardiovascular dynamic control. Increases in body weight to ∼150% of control led to a gradual increase in mean arterial pressure to 17 ± 3 mmHg above control (100 ± 2 mmHg) after 4 wk on the high-fat diet. In contrast to the gradual increase in arterial pressure, tachycardia, attenuated chronotropic baroreflex responses, and reduced heart rate variability were manifest within 1–4 days on high-fat intake, reaching 130 ± 4 beats per minute (bpm) (control = 86 ± 3 bpm) and ∼45% and <20%, respectively, of control levels. Subsequently, both baroreflex activation and renal denervation abolished the hypertension. However, only baroreflex activation effectively attenuated the tachycardia and restored cardiac baroreflex sensitivity and heart rate variability. These findings suggest that baroreflex activation therapy may reduce the risk factors for cardiac arrhythmias as well as lower arterial pressure.

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