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

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)

2009 ◽  
Vol 32 (6) ◽  
pp. 251 ◽  
Author(s):  
Vitor E Valenti ◽  
Caio Imaizumi ◽  
Luiz Carlos De Abreu ◽  
Eduardo Colombari ◽  
Monica A Sato ◽  
...  

Purpose: To compare baroreflex sensitivity among conscious rats of the same strain. Methods: Male WKY rats (eight weeks old) were studied. Cannulas were inserted into the abdominal aortic artery through the right femoral artery to measure mean arterial pressure (MAP) and heart rate (HR). Baroreflex gain was calculated as the ratio between variation of HR in function of the MAP variation (?HR/?MAP) tested with a depressor dose of sodium nitroprusside (SNP, 50µg/kg, iv) and with a pressor dose of phenylephrine (PE, 8µg/kg, iv). We divided the rats into four groups: 1) Low bradycardic baroreflex (LB), BG between -1 and -2 bpm/mmHg tested with PE; 2) High bradycardic baroreflex (HB), BG < -2 bpm/mmHg tested with PE; 3) Low tachycardic baroreflex (LT), BG between -1 and -2 bpm/mmHg tested with SNP and; 4) High tachycardic baroreflex (HT), BG < -2 bpm/mmHg tested with SNP. Significant differences were considered for p < 0.05. Results: Approximately 82% of the rats presented reduced bradycardic reflex while 22 showed attenuated tachycardic reflex. No alterations were noted regarding basal MAP and HR, tachycardic and bradycardic peak and HR range. Conclusions: There was alteration in baroreflex sensitivity among rats of the same strain. Care should be taken when interpreting studies employing WKY as a control for the SHR.


2004 ◽  
Vol 286 (1) ◽  
pp. R138-R142 ◽  
Author(s):  
Ulrich Nordheim ◽  
Karl G. Hofbauer

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.


Author(s):  
Baojian Xue ◽  
Yang Yu ◽  
Terry G. Beltz ◽  
Fang Guo ◽  
Robert B. Felder ◽  
...  

Background Prenatal and postnatal insults can induce a physiological state that leaves offspring later in life vulnerable to subsequent challenges (stressors) eliciting cardiometabolic diseases including hypertension. In this study, we investigated whether maternal angiotensin II–induced hypertension in rats sensitizes postweaning high‐fat diet (HFD)‐elicited hypertensive response and whether this is associated with autonomic dysfunction and altered central mechanisms controlling sympathetic tone in offspring. Methods and Results When eating a low‐lard‐fat diet, basal mean arterial pressure of male offspring of normotensive or hypertensive dams were comparable. However, HFD feeding significantly increased mean arterial pressure in offspring of normotensive and hypertensive dams, but the elevated mean arterial pressure induced by HFD was greater in offspring of hypertensive dams, which was accompanied by greater sympathetic tone and enhanced pressor responses to centrally administrated angiotensin II or leptin. HFD feeding also produced comparable elevations in cardiac sympathetic activity and plasma levels of angiotensin II, interleukin‐6, and leptin in offspring of normotensive and hypertensive dams. Reverse transcriptase polymerase chain reaction analyses in key forebrain regions implicated in the control of sympathetic tone and blood pressure indicated that HFD feeding led to greater increases in mRNA expression of leptin, several components of the renin‐angiotensin system and proinflammatory cytokines in offspring of hypertensive dams when compared with offspring of normotensive dams. Conclusions The results indicate that maternal hypertension sensitized male adult offspring to HFD‐induced hypertension. Increased expression of renin‐angiotensin system components and proinflammatory cytokines, elevated brain reactivity to pressor stimuli, and augmented sympathetic drive to the cardiovascular system likely contributed.


2013 ◽  
Vol 305 (7) ◽  
pp. H1080-H1088 ◽  
Author(s):  
Radu Iliescu ◽  
Ionut Tudorancea ◽  
Eric D. Irwin ◽  
Thomas E. Lohmeier

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.


1992 ◽  
Vol 263 (1) ◽  
pp. R89-R94 ◽  
Author(s):  
M. J. Campagnole-Santos ◽  
S. B. Heringer ◽  
E. N. Batista ◽  
M. C. Khosla ◽  
R. A. Santos

The present study was designed to investigate the effect of intracerebroventricular (icv) and intravenous (iv) infusion of angiotensin (ANG)-(1-7), ANG III, and ANG II on the baroreceptor control of heart rate (BHR) in conscious rats. Reflex changes in HR were elicited by bolus iv injection of either phenylephrine or sodium nitroprusside before and within 1 and 3 h of icv infusion of ANG II (n = 10), ANG III (n = 9), ANG-(1-7) (n = 9), or saline (n = 9) at a rate of 3 nmol.7.5 microliter-1.h-1. In another group of animals (n = 23), iv infusion of the same amount of ANG peptides was carried out at a rate of 0.7 ml/h. The average ratio of changes in HR in beats per minute and changes in mean arterial pressure (MAP, mmHg) was used as an index of BHR sensitivity. ANG II and ANG III produced a significant increase in the basal levels of MAP, but only during the first hour of infusion (iv or icv). No significant changes in baseline HR were observed. ANG-(1-7) and saline infusion did not change basal levels of HR or MAP (iv or icv). ANG II (iv and icv) and ANG III (icv) caused a significant decrease in the BHR sensitivity for reflex bradycardia. In contrast, icv infusion of ANG-(1-7) induced a significant increase in BHR sensitivity for reflex bradycardia (-3.0 +/- 0.3, 1 h, and -2.8 +/- 0.1 beats.min-1.mmHg-1, 3 h vs. -2.1 +/- 0.2 beats.min-1.mmHg-1, before infusion).(ABSTRACT TRUNCATED AT 250 WORDS)


2021 ◽  
Vol 12 (7) ◽  
pp. 64-68
Author(s):  
Nitisha Chakraborty ◽  
Sankar Roy ◽  
Debajyoti Sur ◽  
Arunava Biswas ◽  
Dipasri Bhattacharya ◽  
...  

Background: Cardiovascular stress due to reflex sympathetic over activity is a great concern during laryngoscopy and endotracheal intubation. Aims and Objectives: To compare the efficacy and safety of esmolol and verapamil for attenuation of hemodynamic effects (heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure) due to laryngoscopy and endotracheal intubation in elective surgical cases. Materials and Methods: A prospective, randomized, double blinded, controlled study was conducted on 60 patients divided equally into 30 each receiving esmolol (2 mg/kg body weight) and verapamil (0.1 mg/kg body weight) respectively. Heart rate, systolic and diastolic blood pressure and mean arterial pressure were recordedat pre-operative stage, after administration of the study drugs, immediately after intubation and at 1 ,3 ,5 minutes after intubation. Data collected were statistically analyzed. Results: The mean systolic blood pressure was lower in the esmolol group at all times of estimation compared with the verapamil group and the difference was at the time of intubation (p value <0.001).The mean diastolic blood pressure was lower in the esmolol group at all times of estimation compared to the verapamil group which was not statistically significant at any time of estimation. The mean arterial pressure was significantly lower at the time of immediately after intubation (p<0.001) in esmolol as compared to verapamil group. Adverse effects in both the study groups were insignificant. Conclusion: Esmololand Verapamil can effectively attenuate the cardiovascular stress to laryngoscopy and endotracheal intubation with the former appears to be a better alternative from efficacy and safety perspectives.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Lilei Yu ◽  
XiaoYa Zhou ◽  
Songyun Wang ◽  
Zhuo Wang ◽  
Bing Huang ◽  
...  

Introduction: Obesity is associated with hypertension and increased renal sympathetic nervous activity, Our recent study indicated that autonomic denervation could be induced by nanoparticles.In addition, non-toxic fragment of tetanus toxin, known as tetanus toxin C fragment(TTC), which demonstrates extremely high affinity binding to the surfaces of neurons. Hypothesis: This study was to test the hypothesis that renal denervation with TTC-conjugated nanoparticles could attenuate hypertension associated with obesity . Methods: TTC-conjugated nanoparticles and neurotoxic agent (N-isopropylacrylamide monomer) were synthesized. We determined the hemodynamic responses to a high-fat diet in control (n = 6) and renal-denervated by nanoparticles (n = 8) chronically instrumented dogs. After a control period of 7 days, dogs were placed on a high-fat diet for 5 weeks. a modified balloon catheter will be advanced in the target renal artery segment to allow nanoparticles permeating into vascular wall, after that the moving of nanoparticles will be guided by outside magnetic filed towards renal sympathetic nerve.Blood pressure(BP),heart rate variability (HRV),serum norepinephrine (NE) were measured. Pathological examinations were performed on all retrieved samples. Results: In response to a high-fat diet, body weight increased from 17.6 ± 2.4 to 24.8 ± 1.8 kg in the control group. Heart rate increased from 92 ± 6 to 118 ± 10 beats per minute in the control group. BP increased significantly from 105 ± 5 to 139 ± 4 mm Hg in the control group. In contrast, 5 weeks of a high-fat diet in the renal denervation group did not significantly increase body weight(which went from 18.3 ± 2.5 to 19 ± 2.1 mm Hg), Heart rate (which went from 87 ± 3 to 89 ± 6 mm Hg) and BP (which went from 107 ± 3 to 109 ± 6 mm Hg). sympathetic indices of HRV, serum NE, renal sympathetic activity and the expression of c-fos protein in renal sympathetic nerve was significantly lower in the renal denervation group. A histological examination revealed the disruption of nerve fibers, necrosis of Schwann cells and neurons, and apparent denervation in denervation group. Conclusions: Our results indicate that Renal denervation by TTC-conjugated nanoparticles could attenuate hypertension associated with obesity.


2004 ◽  
Vol 286 (2) ◽  
pp. R350-R358 ◽  
Author(s):  
R. J. Stubbs ◽  
D. A Hughes ◽  
A. M. Johnstone ◽  
S. Whybrow ◽  
G. W. Horgan ◽  
...  

We assessed the effect of no exercise (Nex; control) and high exercise level (Hex; ∼4 MJ/day) and two dietary manipulations [a high-fat diet (HF; 50% of energy, 700 kJ/100 g) and low-fat diet (LF; 20% of energy, 300 kJ/100 g)] on compensatory changes in energy intake (EI) and energy expenditure (EE) over 7-day periods. Eight lean men were each studied four times in a 2 × 2 randomized design. EI was directly quantified by weight of food consumed. EE was assessed by heart rate (HR) monitoring. Body weight was measured daily. Mean daily EE was 17.6 and 11.5 MJ/day ( P < 0.001) on the pooled Hex and Nex treatments, respectively. EI was higher on HF diets (13.4 MJ/day pooled) compared with the LF diets (9.0 MJ/day). Regression analysis showed that these energy imbalances induced significant compensatory changes in EB over time of ∼0.3-0.4 MJ/day ( P < 0.05). These were due to changes in both EI and EE in the opposite direction to the perturbation in energy balance. These changes were significant, small but persistent, amounting to ∼0.2 and ∼0.35 MJ/day for EI and EE, respectively.


2019 ◽  
Vol 44 (4) ◽  
pp. 628-642 ◽  
Author(s):  
Liying Gong ◽  
Fenglin Jiang ◽  
Zhihui Zhang ◽  
Xinguo Wang ◽  
Hui Li ◽  
...  

Background/Aims: Catheter-based renal denervation (RDN) has emerged as an innovative interventional approach for reducing blood pressure (BP), suppressing ventricular substrate remodeling, and attenuating heart failure, which suggests that it might reduce kidney fibrosis in a canine model of high-fat diet-induced hypertension. This study thus sought to assess whether RDN could reduce kidney fibrosis and halt the progression of renal impairment in a canine model of high-fat diet-induced hypertension. Methods: Thirty-two beagles were randomized into either the normal control group (normal diet, n = 10) or the hypertension group (high-fat diet, n = 22). After successful establishment of the model, the hypertension model group was randomized to either the RDN group (n = 9) or the sham-surgery group (n = 8). Renal artery angiography, BP, heart rate (HR), and blood and urine biochemistry results were assessed at 1, 3, and 6 months after surgery. Canines were sacrificed at 6 months after surgery. The extent of kidney interstitial fibrosis, transforming growth factor-beta 1, alpha-smooth muscle actin, connective tissue growth factor, and E-cadherin protein were measured. Results: The group fed a high-fat diet had significantly (p ˂ 0.05) increased body weight, BP, and HR and higher levels of urine albumin, serum noradrenaline (NE), and angiotensin II (AngII) than the control group. The sham-surgery group and RDN group also had higher levels than the control group (p ˂ 0.05). Compared with the sham-surgery group, the RDN group had lower BP, urine albumin, serum NE, and AngII and less fibrotic tissue (all p ˂ 0.05). Conclusion: RDN reduced BP, slowed progression of albuminuria, and suppressed renal remodeling in a canine model of high-fat diet-induced hypertension.


1991 ◽  
Vol 260 (4) ◽  
pp. H1106-H1112 ◽  
Author(s):  
S. Itoh ◽  
M. van den Buuse

Effect of centrally administered endothelins (ETs) on cardiovascular regulation was investigated in conscious normotensive rats. ET-1, ET-2, or ET-3 was injected through a cannula into the cisterna magna, and mean arterial pressure (MAP) and heart rate (HR) were measured through a cannula in the femoral artery. Baroreceptor HR reflex was measured by monitoring the changes in HR in response to changes in MAP induced by slow intravenous injection of phenylephrine or nitroprusside. MAP and HR responses were then analyzed in individual animals by sigmoidal curve fitting. Intracisternal (ic) administration of ET-1 did not change resting MAP or HR at doses of 2.5 or 25 pmol/kg. The higher dose of ET-1 induced a significant increase of baroreflex sensitivity without a change of HR range. Sympathetic and vagal components of the baroreflex were examined by testing reflex responses after pretreatment with methylatropine (0.5 mg/kg iv) and atenolol (1.0 mg/kg iv), respectively. An increased baroreflex sensitivity was observed after ET-1 treatment in the atenolol-treated rats but not in the methylatropine-treated rats, suggesting that the peptide selectively affected the vagal component of the reflex. Intravenous 25 pmol/kg ET-1 did not cause an increase in baroreflex sensitivity. Neither ET-2 nor ET-3 (25 pmol/kg ic) induced changes in resting MAP or HR, but both significantly increased baroreflex sensitivity without changes in HR range. Order of potency of the ETs on baroreflex gain was ET-3 greater than or equal to ET-1 greater than ET-2. In conclusion, ETs at doses that do not change resting values for MAP or HR, may induce significant centrally mediated sensitization of the baroreceptor HR reflex.(ABSTRACT TRUNCATED AT 250 WORDS)


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