Insulin versus Lipid Emulsion in a Rabbit Model of Severe Propranolol Toxicity: A Pilot Study

Background and objective. Beta-blocker overdose may result in intractable cardiovascular collapse despite conventional antidotal treatments. High dose insulin/glucose (ING), and more recently intravenous lipid emulsion (ILE), have been proposed as potentially beneficial therapies in beta blocker intoxication. We compare efficacy of the novel antidotes ING, with ILE, in a rabbit model of combined enteric/intravenous propranolol toxicity.Methods. Sedated, mechanically ventilated and invasively monitored New Zealand White rabbits underwent mini-laparotomy and enterostomy formation with 40 mg/kg propranolol instilled into the proximal small bowel. At 30 minutes propranolol infusion was commenced at 4 mg/kg/hr and continued to a target mean arterial pressure (MAP) of 50% baseline MAP. Animals were resuscitated with insulin at 3 U/kg plus 0.5 g/kg glucose (ING group), or 10 mL/kg 20% Intralipid (ILE group).Results. Rate pressure product (RPP; RPP = heart rate × mean arterial pressure) was greatest in the ING group at 60 minutes (P<.05). A trend toward greater heart rate was observed in the ING group (P=.06). No difference was observed in survival between groups (4/5 ING versus 2/5 ILE;P=.524).Conclusions. High dose insulin resulted in greater rate pressure product compared with lipid emulsion in this rabbit model of severe enteric/intravenous propranolol toxicity.

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Effects of delta-opioid receptor agonist pretreatment on the cardiotoxicity of bupivacaine in rats

BMC Anesthesiology ◽

10.1186/s12871-022-01568-x ◽

2022 ◽

Vol 22 (1) ◽

Author(s):

Chenran Wang ◽

Shen Sun ◽

Jing Jiao ◽

Xinhua Yu ◽

Shaoqiang Huang

Keyword(s):

Heart Rate ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Opioid Receptor ◽

Receptor Agonist ◽

Lipid Emulsion ◽

Delta Opioid Receptor ◽

Heart Rate Reduction ◽

Rate Reduction ◽

Opioid Receptor Agonist

Abstract Background Delta-opioid receptor is widely expressed in human and rodent hearts, and has been proved to protect cardiomyocytes against ischemia/reperfusion and heart failure. The antagonist of delta-opioid receptor could block the rescue effect of lipid emulsion against local anesthetic cardiotoxicity. However, no evidence is available for the direct effect of delta-opioid-receptor agonists on the cardiotoxicity of local anesthetics. Methods Anesthetized Sprague Dawley rats were divided into five groups. Group NS received 2 ml·kg−1·min−1 normal saline, group LE received 2 ml·kg−1·min−1 30% lipid emulsion and group BW received 0.1, 1.0, or 5.0 mg/kg BW373U86, a delta-opioid-receptor agonist, for 5 min. Then 0.5% bupivacaine was infused intravenously at a rate of 3.0 mg·kg−1·min−1 until asystole. The time of arrhythmia, 50% mean arterial pressure-, 50% heart rate-reduction and asystole were recorded, and the dose of bupivacaine at each time point was calculated. Results All three different doses of BW373U86 did not affect the arrhythmia, 50% mean arterial pressure-reduction, 50% heart rate-reduction and asystole dose of bupivacaine compared with group NS. 30% LE significantly increased the bupivacaine threshold of 50% mean arterial pressure-reduction (17.9 [15.4–20.7] versus 7.2 [5.9–8.7], p = 0.018), 50% heart rate-reduction (18.7 ± 4.2 versus 8.8 ± 1.7, p < 0.001) and asystole (26.5 [21.0–29.1] versus 11.3 [10.7–13.4], p = 0.008) compared with group NS. There was no difference between group LE and group NS in the arrhythmia dose of bupivacaine (9.9 [8.9–11.7] versus 5.6 [4.5–7.0], p = 0.060). Conclusions Our data show that BW373U86 does not affect the cardiotoxicity of bupivacaine compared with NS control in rats. 30% LE pretreatment protects the myocardium against bupivacaine-induced cardiotoxicity.

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Hypertension induced by blockade of ETB receptors in conscious nonhuman primates: role of ETAreceptors

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00346.2002 ◽

2002 ◽

Vol 283 (4) ◽

pp. H1555-H1561 ◽

Cited By ~ 26

Author(s):

Glenn A. Reinhart ◽

Lee C. Preusser ◽

Sandra E. Burke ◽

Jerry L. Wessale ◽

Craig D. Wegner ◽

...

Keyword(s):

Heart Rate ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Nonhuman Primates ◽

High Dose ◽

Cynomolgus Monkeys ◽

Selective Antagonist ◽

Sustained Hypertension ◽

Endothelin B

The role of endothelin-B (ETB) receptors in circulatory homeostasis is ambiguous, reflecting vasodilator and constrictor effects ascribed to the receptor and diuretic and natriuretic responses that could oppose the hypertensive effects of ET excess. With the use of conscious, telemetry-instrumented cynomolgus monkeys, we characterized the hypertension produced by ETB blockade and the role of ETA receptors in mediating this response. Mean arterial pressure (MAP) and heart rate (HR) were measured 24 h/day for 24 days under control conditions and during administration of the ETB-selective antagonist A-192621 (0.1, 1.0, and 10 mg/kg bid, 4 days/dose) followed by coadministration of the ETAantagonist atrasentan (5 mg/kg bid) + A-192621 (10 mg/kg bid) for another 4 days. High-dose ETB blockade increased MAP from 79 ± 3 (control) to 87 ± 3 and 89 ± 3 mmHg on the first and fourth day, respectively; HR was unchanged, and plasma ET-1 concentration increased from 2.1 ± 0.3 pg/ml (control) to 7.24 ± 0.99 and 11.03 ± 2.37 pg/ml. Atrasentan + A-192621 (10 mg/kg) decreased MAP from hypertensive levels (89 ± 3) to 75 ± 2 and 71 ± 4 mmHg on the first and fourth day, respectively; plasma ET-1 and HR increased to 26.64 ± 3.72 and 28.65 ± 2.89 pg/ml and 113 ± 5 (control) to 132 ± 5 and 133 ± 7 beats/min. Thus systemic ETB blockade produces a sustained hypertension in conscious nonhuman primates, which is mediated by ETA receptors. These data suggest an importance clearance function for ETB receptors, one that influences arterial pressure homeostasis indirectly by reducing plasma ET-1 levels and minimizing ETA activation.

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Abstract P234: 2-Methoxyestradiol Attenuates Angiotensin II Induced Hypertension: A Novel Paradigm

Hypertension ◽

10.1161/hyp.70.suppl_1.p234 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Yong Zhang ◽

Benard Ogola ◽

Laxmi Iyer ◽

Vardan Karamyan ◽

Thomas Thekkumkara

Keyword(s):

Heart Rate ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Heart Weight ◽

Rate Pressure Product ◽

Kidney Cortex ◽

Control Group ◽

Binding Studies ◽

Wky Rats ◽

Induced Hypertension

Estrogen metabolite 2-methoxyestradiol (2ME2) has therapeutic potential in a number of cardiovascular disorders, including hypertension. However, specific or potential targets remains to be determined. In this study, animals were surgically implanted with PA-C40 telemetry in the intra-aortic vessel and 2ME2 (20 mg/kg/day, i.p. injection) effects in AngII infused Wistar-Koyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were determined. In WKY rats 2ME2 treatment resulted in significant reduction in AngII induced blood pressure (BP) compared to vehicle control (systolic; 143.69 ± 2.68 vs. 169.75 ± 1.93 mm Hg, diastolic; 99.91 ± 2.49 vs. 120.16 ± 1.25 mm Hg, and mean arterial pressure; 118.94 ± 2.52 vs. 142.73 ± 1.47 mm Hg). We observed a decrease in heart rate in 2ME2 exposed animals compared to control group (272.67 ± 9.88 vs. 329.12 ± 6.14 BPM). In addition, 2ME2 mediated reduction in workload of the heart when we calculated the rate pressure product or pressure rate index by 13.46 ± 2.32 indicating that 2ME2 can reduce AngII induced hemodynamic stress of the heart. [ 3 H]AngII binding studies showed that in kidney cortex AT1R expression was inhibited by 2ME2 treatment compared to control (2112 ± 71 vs. 3341 ± 248 DPM/mg protein). In a separate 5-week study, 2ME2-treated SHRs displayed significant reduction in diastolic BP (114.31 ± 0.66 vs. 123.28 ± 0.70 mm Hg) and mean arterial pressure (146.35 ± 0.67 vs. 151.54 ± 0.89 mm Hg) without significant change in systolic BP compare to the vehicle treated animals. Moreover, we found significant decrease in heart rate in 2ME2-treated animals (290.03 ± 2.69 vs. 312.92 ± 1.50 BPM). Analyses of kidney cortical tissue revealed downregulation of AT1R expression after 2ME2 treatments (20227 ± 2211 vs. 9515 ± 2115 DPM/mg protein). Consistent with the reduction in BP, the indicators of cardiac hypertrophy including heart weight (1.28 ± 0.08 vs. 0.99 ± 0.02 gram), cardiac collagen deposit and α-smooth muscle actin (α-SMC) positive myofibroblasts were decreased. The data demonstrate for the first time that 2ME2 control BP through downregulation of AT1R in kidney and heart rate, which may provide an insight to the mechanism(s) of cardioprotective effects of 2ME2 through the blockade of AngII induced hypertension.

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Comparison of Intravenous Lignocaine and Dexmedetomidine for Attenuation of Hemodynamic Stress Response to Laryngoscopy and Endotracheal Intubation

Journal of Evolution of Medical and Dental Sciences ◽

10.14260/jemds/2021/240 ◽

2021 ◽

Vol 10 (16) ◽

pp. 1123-1129

Author(s):

Deepti N. Anandani ◽

Manisha S. Kapdi ◽

Ami D. Patel ◽

Pratik Jain

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Stress Response ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Systolic Blood Pressure ◽

Diastolic Blood Pressure ◽

Endotracheal Intubation ◽

Normal Saline ◽

Rate Pressure Product

BACKGROUND The purpose of the present study was to evaluate the efficacy of intravenous lignocaine 1.5 mg / kg & intravenous dexmedetomidine 1 mcg / kg for attenuating the haemodynamic response to laryngoscopy & endotracheal intubation in patients undergoing elective surgery under general anaesthesia. METHODS In this prospective randomised, comparative, clinical study, 60 patients were randomly divided into 2 groups, among them 30 patients were given infusion of 1.5 mg / kg IV lignocaine, diluted to 10 ml with normal saline, 3 minutes before intubation & 30 patients were given infusion of dexmedetomidine 1 mcg / kg diluted to 25 ml in normal saline over 10 minutes through infusion pump before induction. The heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, rate pressure product, oxygen saturation were measured at baseline, after study drug intubation at L + 1, L + 3, L + 5, L + 7 & L + 10 (L is onset of laryngoscopy). Statistical analysis was done by using descriptive & inferential statistics using chisquare test, Students paired & unpaired t test to find out the significance of the five variables namely mean heart rate (HR), mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP), mean arterial pressure (MAP) and mean rate pressure product (RPP). RESULTS Dexmedetomidine provided better blunting of stress response during laryngoscopy and intubation without causing clinically significant respiratory depression, bradycardia or hypotension. It is better in achieving a low RPP, which is a good predictor of myocardial oxygen consumption. Dexmedetomidine provides better cardio-protection in patients against pressure response than lignocaine. CONCLUSIONS In these 60 patients, dexmedetomidine (1 mcg / kg) was found to be superior to lignocaine (1.5 mg / kg) for attenuation of pressor response. KEY WORDS Laryngoscopy, Endotracheal Intubation, Dexmedetomidine, Lignocaine, Rate Pressure Product

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Use of Gabapentin, Esmolol or Their Combination to Attenuate Haemodynamic Response to Laryngoscopy and Intubation

Kathmandu University Medical Journal ◽

10.3126/kumj.v9i4.6336 ◽

2012 ◽

Vol 9 (4) ◽

pp. 238-243 ◽

Cited By ~ 1

Author(s):

G S Shrestha ◽

M N Marhatta ◽

R Amatya

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Systolic Blood Pressure ◽

Normal Saline ◽

Study Drug ◽

Haemodynamic Response ◽

Rate Pressure Product ◽

Significant Difference

Background Laryngoscopy and intubation increases blood pressure and heart rate. Objective The study aims to investigate the effect and safety of gabapentin, esmolol or their combination on the haemodynamic response to laryngoscopy and intubation. Methods A total of 72 patients undergoing elective surgery were randomly allocated to one of the four groups. First study drug was administered orally as gabapentin 1200mg or placebo. Second study drug was administered intravenously as esmolol 1.5mg/kg or normal saline. Heart rate, rate pressure product, systolic blood pressure and mean arterial pressure were recorded at baseline and at zero, one, three and five minutes after tracheal intubation. Results Baseline values were compared with the values at various time intervals within the same group. In group PE (placebo, esmolol), there was significant decrease in heart rate and rate pressure product at five minutes. In group GN (gabapentin, normal saline), there was significant decrease in systolic blood pressure and mean arterial pressure at five minutes. In group GE (gabapentin, esmolol), there was significant decrease in heart rate at zero, three and five minutes. Systolic blood pressure, mean arterial pressure and rate pressure product was significantly lower at three and five minutes. In group PN (placebo, normal saline), there was significant increase in heart rate at zero, one, three and five minutes; systolic blood pressure at zero and one minutes; mean arterial pressure at zero and one minutes & rate pressure product at zero, one and three minutes. In group GN (gabapentin, normal saline), there was significant increase in heart rate at zero, one and three minutes & rate pressure product at zero, one and three minutes. In group PE (placebo, esmolol), there was significant increase in systolic blood pressure at zero and one minutes & mean arterial pressure at zero and one minutes. However, in group GE (gabapentin, esmolol) none of the variables showed statistically significant increase at any time. Inter-group comparison was made for each time point. At zero minute, there was significant difference in heart rate between groups PN and GE, GN and PE & GN and GE Significant difference was also noted in rate pressure product between PN and GE at zero minute. At one minute there was difference in heart rate between PN and PE, PN and GE, GN and PE & between GN and GE. Significant difference was observed in rate pressure product between PN and PE & between PN and GE at one minute. No significant side effects of the study drugs were observed. ConclusionsCombination of gabapentin and esmolol in this study design is safe and better attenuates both the pressor and tachycardic response to laryngoscopy and intubation, than either agent alone.DOI: http://dx.doi.org/10.3126/kumj.v9i4.6336 Kathmandu Univ Med J 2011;9(4):238-43

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Role of intravenous esmolol, fentanyl and lignocaine for attenuation of stress response in tracheal intubation - a comparative study

Journal of the Bangladesh Society of Anaesthesiologists ◽

10.3329/jbsa.v26i1.19810 ◽

2014 ◽

Vol 26 (1) ◽

pp. 12-19

Author(s):

Nurul Islam ◽

Amirul Islam ◽

Idris Ali ◽

Mohiuddin Shumon ◽

Mozaffor Hossain ◽

...

Keyword(s):

Heart Rate ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Endotracheal Intubation ◽

Haemodynamic Response ◽

Rate Pressure Product ◽

Mean Values ◽

Group A ◽

The Mean ◽

Group B

Background Endotracheal intubation is an essential part of safe airway management but this stimulates the patients airway reflexes and predictably leads to haemodynamic derangement. Many drugs have been suggested in modifying in haemodynamic responses to laryngoscopy and intubation. Objectives To assess efficacy of three drugs - esmolol, fentanyl and lignocaine and to assess which one is more effective to attenuate haemodynamic response to direct laryngoscopy and endotracheal intubation. Methods A total number of 90 patients ASA class I and II were selected randomly as per inclusion and exclusion criteria in three groups, 30 patients in each group. Group A received esmolol 1.5mg/kg in the volume of 10ml (with distil water) 2min before intubation, group B received fentanyl 1.5mg/kg IV 5min before intubation and group C received lignocaine 1.5mg/kg IV 90 sec before intubation. Per-operative data were recorded at 1min, 2min, 5min and 10min after intubation. Results The mean heart rate, systolic, diastolic,mean arterial pressure before starting anaesthesia were similar in group-A (esmolol), B(fentanyl) and C(lignocaine). The mean values of heart rate and rate pressure product were significantly lower in group A(Esmolol) at 1 and 2 minute than group B(fentanyl) and at 1, 2 and 5 minute than group C(lignocaine). The mean values of systolic, diastolic and mean arterial pressure were slightly lower in group A(esmolol) at 5 minute than group B(fentanyl) and significantly lower at 1, 2 and 5 minute than group C(lignocaine). Conclusion Esmolol 1.5mg/kg is superior to lignocaine 1.5mg/kg for attenuation of haemodynamic response (HR, SBP, DBP, RPP and MAP) to laryngoscopy and endotracheal intubation and also superior to fentanyl for attenuation of HR and RPP. DOI: http://dx.doi.org/10.3329/jbsa.v26i1.19810 Journal of Bangladesh Society of Anaesthesiologists 2013; 26(1): 12-19

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Effect of Dexmedetomidine on Perioperative Stress Response and Immune Function in Patients With Tumors

Technology in Cancer Research & Treatment ◽

10.1177/1533033820977542 ◽

2020 ◽

Vol 19 ◽

pp. 153303382097754

Author(s):

Lihong Zheng ◽

Juan Zhao ◽

Likun Zheng ◽

Shuangfeng Jing ◽

Xiaoting Wang

Keyword(s):

Heart Rate ◽

Stress Response ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Immune Function ◽

Spontaneous Respiration ◽

General Anesthetics ◽

Ifn Γ ◽

Group D ◽

Perioperative Stress

Objective: This study aims to investigate the effect of dexmedetomidine on perioperative stress response and immune function in patients with tumors. Methods: Sixty patients who underwent selective radical gastrectomy for cancer were randomly divided into 3 groups: remifentanil group (group R), dexmedetomidine group (group D), and sufentanil group (group S). Remifentanil, dexmedetomidine, and sufentanil were used as general anesthetics. Endotracheal intubation and mechanical ventilation were performed after the spontaneous respiration disappeared. Then, the data were recorded, and blood samples were collected at all time points. Results: The heart rate significantly increased ( P < 0.05) at T1 in group S, and both heart rate and mean arterial pressure significantly increased ( P < 0.05) in group R when compared to group D. The heart rate significantly increased ( P < 0.05) at T2 in group S and group R. Furthermore, the heart rate significantly increased ( P < 0.05) at T3 and T4 in group S and group R. Intra-group comparison: The heart rate at T1–T4 and mean arterial pressure at T1–T4 significantly increased ( P < 0.05) in group S, and the heart rate at T1 and T4, and mean arterial pressure at T2–T4 significantly increased ( P < 0.05) in group R when compared to T0. The serum IL-6, IFN-γ, and β-EP significantly increased ( P < 0.05) at T0’ in group S and group R when compared to group D. Blood glucose, and serum IL-10, IFN-γ, and β-EP significantly increased ( P < 0.05), while IL-18 significantly decreased ( P < 0.05) at T1’ in group S and group R. Conclusion: Continuous infusion of dexmedetomidine in combination with the inhalation of sevoflurane is superior to sevoflurane + remifentanil or sufentanil in patients undergoing tumor surgery.

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Preclinical Pharmacology in the Rhesus Monkey of CW 1759-50, a New Ultra-short Acting Nondepolarizing Neuromuscular Blocking Agent, Degraded and Antagonized by L-Cysteine

Anesthesiology ◽

10.1097/aln.0000000000002408 ◽

2018 ◽

Vol 129 (5) ◽

pp. 970-988 ◽

Cited By ~ 2

Author(s):

John J. Savarese ◽

Hiroshi Sunaga ◽

Jeff D. McGilvra ◽

Matthew R. Belmont ◽

Matthew T. Murrell ◽

...

Keyword(s):

Heart Rate ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Neuromuscular Blockade ◽

Blocking Agent ◽

Neuromuscular Blocking ◽

Neuromuscular Blocking Agent ◽

Duration Of Action ◽

Short Acting ◽

Circulatory Effects

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Structure–activity studies were performed to identify a new neuromuscular blocking agent retaining the ultra-short acting characteristics of gantacurium, including degradation and reversal by l-cysteine, but lacking its histaminoid properties in man. CW 1759-50 has emerged from this program. Methods Adduction of CW 1759-50 with l-cysteine was studied by high-performance liquid chromatography and mass spectrometry. Institutional Animal Care and Use Committee–approved comparisons of CW 1759-50 to gantacurium were performed in rhesus monkeys. ED95 for neuromuscular blockade was established. Spontaneous recovery was compared to reversal by l-cysteine in paired studies of boluses or infusions. In addition, changes in mean arterial pressure and heart rate after very large doses of 15 to 60 × ED95 were compared. Results The half-time of adduction of l-cysteine to CW 1759-50 in vitro was 2.3 min. The ED95 of CW 1759-50 was 0.069 ± 0.02 mg/kg; ED95 of gantacurium was 0.081 ± 0.05 mg/kg (P = 0.006). Duration of action (recovery to 95% twitch height after 98 to 99% blockade) was as follows: CW 1759-50, 8.2 ± 1.5 min; and gantacurium, 7.4 ± 1.9 min; (n = 8 and 9, P = 0.355). Administration of l-cysteine (30 mg/kg) shortened recovery (i.e., induced reversal) from CW 1759-50 after boluses or infusions (P always less than 0.0001). Recovery intervals (5 to 95% twitch) ranged from 6.1 to 6.7 min (and did not differ significantly) after boluses of 0.10 to 0.50 mg/kg, as well as control infusions (P = 0.426 by analysis of variance). Dose ratios comparing changes of 30% in mean arterial pressure or heart rate to ED95 for neuromuscular blockade (ED 30% Δ [mean arterial pressure or heart rate]/ED95) were higher for CW 1759-50 than for gantacurium. Conclusions CW 1759-50, similar to gantacurium, is an ultra-short acting neuromuscular blocking agent, antagonized by l-cysteine, in the monkey. The circulatory effects, however, are much reduced in comparison with gantacurium, suggesting a trial in humans.

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Hypotensive and Regional Haemodynamic Effects of Exercise, Fasted and after Food, in Human Sympathetic Denervation

Clinical Science ◽

10.1042/cs0940049 ◽

1998 ◽

Vol 94 (1) ◽

pp. 49-55 ◽

Cited By ~ 11

Author(s):

Sharmini Puvi-Rajasingham ◽

Gareth D. P. Smith ◽

Adeola Akinola ◽

Christopher J. Mathias

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Superior Mesenteric Artery ◽

Vascular Resistance ◽

Mesenteric Artery ◽

Autonomic Failure ◽

Sympathetic Denervation ◽

Stroke Distance

1. In human sympathetic denervation due to primary autonomic failure, food and exercise in combination may produce a cumulative blood pressure lowering effect due to simultaneous splanchnic and skeletal muscle dilatation unopposed by corrective cardiovascular reflexes. We studied 12 patients with autonomic failure during and after 9 min of supine exercise, when fasted and after a liquid meal. Standing blood pressure was also measured before and after exercise. 2. When fasted, blood pressure fell during exercise from 162 ± 7/92 ± 4 to 129 ± 9/70 ± 5 mmHg (mean arterial pressure by 22 ± 5%), P < 0.0005. After the meal, blood pressure fell from 159 ± 8/88 ± 6 to 129 ± 6/70 ± 4 mmHg (mean arterial pressure by 22 ± 3%), P < 0.0001, and further during exercise to 123 ± 6/61 ± 3 mmHg (mean arterial pressure by 9 ± 3%), P < 0.01. The stroke distance—heart rate product, an index of cardiac output, did not change after the meal. During exercise, changes in the stroke distance—heart rate product were greater when fasted. 3. Resting forearm and calf vascular resistance were higher when fasted. Calf vascular resistance fell further after exercise when fasted. Resting superior mesenteric artery vascular resistance was lower when fed; 0.19 ± 0.02 compared with 032 ± 0.06, P < 0.05. After exercise, superior mesenteric artery vascular resistance had risen by 82%, to 0.53 ± 0.12, P < 0.05 (fasted) and by 47%, to 0.29 ± 0.05, P < 0.05 (fed). 4. On standing, absolute levels of blood pressure were higher when fasted [83 ± 7/52 ± 7 compared with 71 ± 2/41 ± 3 (fed), each P < 0.05]. Subjects were more symptomatic on standing post-exercise when fed. 5. In human sympathetic denervation, exercise in the fed state lowered blood pressure further than when fasted and worsened symptoms of postural hypotension.

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Angiotensin II induces insulin resistance independent of changes in interstitial insulin

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1999.277.5.e920 ◽

1999 ◽

Vol 277 (5) ◽

pp. E920-E926 ◽

Cited By ~ 24

Author(s):

Joyce M. Richey ◽

Marilyn Ader ◽

Donna Moore ◽

Richard N. Bergman

Keyword(s):

Insulin Resistance ◽

Heart Rate ◽

Blood Flow ◽

Angiotensin Ii ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Glucose Uptake ◽

Peripheral Resistance ◽

Glucose Turnover ◽

Ang Ii

We set out to examine whether angiotensin-driven hypertension can alter insulin action and whether these changes are reflected as changes in interstitial insulin (the signal to which insulin-sensitive cells respond to increase glucose uptake). To this end, we measured hemodynamic parameters, glucose turnover, and insulin dynamics in both plasma and interstitial fluid (lymph) during hyperinsulinemic euglycemic clamps in anesthetized dogs, with or without simultaneous infusions of angiotensin II (ANG II). Hyperinsulinemia per se failed to alter mean arterial pressure, heart rate, or femoral blood flow. ANG II infusion resulted in increased mean arterial pressure (68 ± 16 to 94 ± 14 mmHg, P < 0.001) with a compensatory decrease in heart rate (110 ± 7 vs. 86 ± 4 mmHg, P < 0.05). Peripheral resistance was significantly increased by ANG II from 0.434 to 0.507 mmHg ⋅ ml−1⋅ min ( P < 0.05). ANG II infusion increased femoral artery blood flow (176 ± 4 to 187 ± 5 ml/min, P < 0.05) and resulted in additional increases in both plasma and lymph insulin (93 ± 20 to 122 ± 13 μU/ml and 30 ± 4 to 45 ± 8 μU/ml, P < 0.05). However, glucose uptake was not significantly altered and actually had a tendency to be lower (5.9 ± 1.2 vs. 5.4 ± 0.7 mg ⋅ kg−1⋅ min−1, P > 0.10). Mimicking of the ANG II-induced hyperinsulinemia resulted in an additional increase in glucose uptake. These data imply that ANG II induces insulin resistance by an effect independent of a reduction in interstitial insulin.

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