scholarly journals Insulin-regulated aminopeptidase deficiency impairs cardiovascular adaptations and placental development during pregnancy

2020 ◽  
Vol 134 (23) ◽  
pp. 3213-3228
Author(s):  
Sarah L. Walton ◽  
Katrina M. Mirabito Colafella ◽  
Aneesa Ansari ◽  
Siew Yeen Chai ◽  
Kate M. Denton
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Knockout Mice ◽  
Late Gestation ◽  
Wild Type ◽  
Placental Development ◽  
Junctional Zone ◽  
Fluid Handling ◽  
Arterial Pressure Regulation

Abstract Insulin-regulated aminopeptidase (IRAP), an enzyme that cleaves vasoactive peptides including oxytocin and vasopressin, is suggested to play a role in pregnancy and the onset of preeclampsia. Our aim was to examine the contribution of IRAP to arterial pressure regulation and placental development during pregnancy in mice. Mean arterial pressure and heart rate were measured via radiotelemetry in 12-week-old female wild-type and IRAP knockout mice. Females were time-mated with males of the same genotype. Placentae were collected at embryonic day 18.5 for histological analysis. Basal heart rate was ∼40 bpm lower in IRAP knockout females compared with wild-type females. The increase in heart rate across gestation was greater in IRAP knockout females than wild-type females. Neither basal nor gestational mean arterial pressure was different between wildtype and IRAP knockout females. Urine output and water intake of IRAP knockout mice were ∼45% less than wild-type mice at late gestation. IRAP deficiency had no effect on fetal weight. Morphological assessment of placentae revealed that IRAP deficiency was associated with reduced labyrinth surface area and accumulation of glycogen in the junctional zone. Our data demonstrate that IRAP deficiency alters maternal fluid handling and impairs placental labyrinth expansion at late gestation, indicating that IRAP contributes to the normal adaptions to pregnancy.

Hemodynamic and hormonal responses to hemorrhage in conscious rabbits at mid- and late gestation

1998 ◽  
Vol 275 (4) ◽  
pp. R1082-R1090 ◽  
Author(s):  
Virginia L. Brooks ◽  
Rebecca R. Quesnell ◽  
Colleen M. Kane ◽  
Lanny C. Keil
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Plasma Renin ◽  
Late Gestation ◽  
Ang Ii ◽  
Pressure Regulation ◽  
Hormonal Responses ◽  
Conscious Rabbits ◽  
The Relationship ◽  
Arterial Pressure Regulation

This study tests the hypothesis that conscious rabbits late in pregnancy (P), but not at midgestation (MP), are less able to maintain arterial pressure during hemorrhage. Blood volume (BV) was elevated ( P < 0.05) by an average of 13 ± 4 (MP) and 35 ± 3% (P). Rabbits were bled in both the nonpregnant (NP) and P state at 2% of the initial BV per minute. The hemorrhage was stopped after arterial pressure decreased. In NP rabbits, arterial pressure was well maintained near control pressures of 70 ± 2 mmHg until 38 ± 2% of the initial BV was removed and then rapidly fell to reach a nadir at 35 ± 2 mmHg. In contrast, in P rabbits, basal arterial pressure was lower (61 ± 2 mmHg; P < 0.05) and gradually decreased to below control after <25% of the initial BV was removed. Moreover, the rapid hypotensive phase was triggered with a lower percent BV removal (33 ± 2%; P < 0.05). Basal heart rate was higher during P (149 ± 5 vs. 189 ± 9 beats/min; P < 0.05), and reflex increases were delayed. The slope of the relationship between arterial pressure and vasopressin was not modified during P, although the line was shifted to a lower pressure ( P < 0.05). Larger increases in plasma renin activity and ANG II concentration were produced during hemorrhage in P rabbits. In contrast, no differences in the changes in arterial pressure, heart rate, and vasopressin were found between NP and MP rabbits during hemorrhage, although increases in renin and ANG II were greater at MP ( P < 0.05). In summary, although P conscious rabbits are less able to maintain blood pressure during hemorrhage, this change is not evident at MP. These data suggest that the factors that mediate the P-induced alterations in arterial pressure regulation are not operative until late in gestation.

scholarly journals Bombesin-like receptor 3 regulates blood pressure and heart rate via a central sympathetic mechanism

2016 ◽  
Vol 310 (7) ◽  
pp. H891-H898 ◽  
Author(s):  
Dalya M. Lateef ◽  
Cuiying Xiao ◽  
Robert J. Brychta ◽  
André Diedrich ◽  
Jurgen Schnermann ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Resting Heart Rate ◽  
Wild Type ◽  
Adrenergic Agonist ◽  
Free Living ◽  
And Control ◽  
G Protein Coupled

Bombesin-like receptor 3 (BRS-3) is an orphan G protein-coupled receptor that regulates energy expenditure, food intake, and body weight. We examined the effects of BRS-3 deletion and activation on blood pressure and heart rate. In free-living, telemetered Brs3 null mice the resting heart rate was 10% lower than wild-type controls, while the resting mean arterial pressure was unchanged. During physical activity, the heart rate and blood pressure increased more in Brs3 null mice, reaching a similar heart rate and higher mean arterial pressure than control mice. When sympathetic input was blocked with propranolol, the heart rate of Brs3 null mice was unchanged, while the heart rate in control mice was reduced to the level of the null mice. The intrinsic heart rate, measured after both sympathetic and parasympathetic blockade, was similar in Brs3 null and control mice. Intravenous infusion of the BRS-3 agonist MK-5046 increased mean arterial pressure and heart rate in wild-type but not in Brs3 null mice, and this increase was blocked by pretreatment with clonidine, a sympatholytic, centrally acting α2-adrenergic agonist. In anesthetized mice, hypothalamic infusion of MK-5046 also increased both mean arterial pressure and heart rate. Taken together, these data demonstrate that BRS-3 contributes to resting cardiac sympathetic tone, but is not required for activity-induced increases in heart rate and blood pressure. The data suggest that BRS-3 activation increases heart rate and blood pressure via a central sympathetic mechanism.

scholarly journals Plasma hyperosmolality and arterial pressure regulation during heating in dehydrated and awake rats

1998 ◽  
Vol 275 (5) ◽  
pp. R1703-R1711 ◽  
Author(s):  
Yasufumi Nakajima ◽  
Hiroshi Nose ◽  
Akira Takamata
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Skin Blood Flow ◽  
Plasma Osmolality ◽  
Cardiovascular Responses ◽  
Pressure Regulation ◽  
Highly Correlated ◽  
Arterial Pressure Regulation

To gain better insights into the effect of dehydration on thermal and cardiovascular regulation during hyperthermia, we examined these regulatory responses during body heating in rats under isosmotic hypovolemia and hyperosmotic hypovolemia. Rats were divided into four groups: normovolemic and isosmotic (C), hypovolemic and isosmotic [L, plasma volume loss (ΔPV) = −20% of control], hypovolemic and less hyperosmotic [HL1, increase in plasma osmolality (ΔPosm) = 23 mosmol/kgH2O, ΔPV = −16%], and hypovolemic and more hyperosmotic (HL2, ΔPosm = 52 mosmol/kgH2O, ΔPV = −17%). Hyperosmolality was attained by subcutaneous injection of hypertonic saline and hypovolemia by intra-arterial injection of furosemide before heating. Then rats were placed in a thermocontrolled box (35°C air temperature, ∼20% relative humidity) for 1–2 h until rectal temperatures (Tre) reached 40.0°C. Mean arterial pressure in L decreased with rise in Tre( P < 0.001), whereas mean arterial pressure remained constant in the other groups. Maximal tail skin blood flow in L, HL1, and HL2 was decreased to ∼30% of that in C ( P < 0.001). Tre threshold for tail skin vasodilation (TVD) was not changed in L, whereas the threshold shifted higher in the HL groups. Trethreshold for TVD was highly correlated with Posm( r = 0.94, P < 0.001). Heart rate in the HL groups increased with rise in Tre( P < 0.001), whereas it remained unchanged in C and L. Cardiovascular responses to heating were not influenced by V1 antagonist in C, L, and HL2. Thus isotonic hypovolemia attenuates maximal tail skin blood flow, whereas hypertonic hypovolemia causes an upward shift of Tre threshold for TVD and an increase in heart rate during hyperthermia. These results suggest that plasma hyperosmolality stimulates pressor responses in the hypovolemic condition that subsequently contribute to arterial pressure regulation during heat stress.

scholarly journals Arterial Pressure and Heart Rate Increase during REM Sleep in Adenosine A2A-Receptor Knockout Mice, but not in Wild-Type Mice

2005 ◽  
Vol 30 (10) ◽  
pp. 1856-1860 ◽  
Author(s):  
Mie Sakata ◽  
Hiroyoshi Sei ◽  
Naomi Eguchi ◽  
Yusuke Morita ◽  
Yoshihiro Urade
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Rem Sleep ◽  
Knockout Mice ◽  
Rate Increase ◽  
Adenosine A2a Receptor ◽  
Wild Type ◽  
Heart Rate Increase ◽  
A2a Receptor ◽  
Adenosine A2a

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

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.

scholarly journals 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

2018 ◽  
Vol 129 (5) ◽  
pp. 970-988 ◽  
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.

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

1998 ◽  
Vol 94 (1) ◽  
pp. 49-55 ◽  
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.

Angiotensin II induces insulin resistance independent of changes in interstitial insulin

1999 ◽  
Vol 277 (5) ◽  
pp. E920-E926 ◽  
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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