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

2002 ◽  
Vol 283 (4) ◽  
pp. H1555-H1561 ◽  
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.

Endothelin and ETA receptors in long-term arterial pressure homeostasis in conscious nonhuman primates

2000 ◽  
Vol 279 (5) ◽  
pp. R1701-R1706 ◽  
Author(s):  
Glenn A. Reinhart ◽  
Lee C. Preusser ◽  
Terry J. Opgenorth ◽  
Craig D. Wegner ◽  
Bryan F. Cox
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Receptor Antagonist ◽  
Nonhuman Primate ◽  
Nonhuman Primates ◽  
Cynomolgus Monkeys ◽  
Endothelin 1 ◽  
Posttreatment Period

This study was designed to quantify the long-term contribution of endogenous endothelin-1 (ET-1) and ETA receptors to the regulation of arterial pressure under normal conditions in nonhuman primates. Therefore, mean arterial pressure (MAP) and heart rate were measured 24 h/day with the use of telemetry techniques in conscious cynomolgus monkeys under control conditions, during administration of an ETA selective receptor antagonist (ABT-627; 5 mg/kg, 2 times a day by mouth, 4 days), and a 6-day posttreatment period. Systemic ETA blockade reduced MAP (24 h) from 89 ± 3 to 82 ± 2 and 79 ± 2 mmHg on days 1 and 4, respectively. Subsequently, MAP remained suppressed for 3 days posttreatment. Heart rate increased from 111 ± 5 to 122 ± 4 and 128 ± 6 beats/min on days 1and 4 of ABT-627, respectively, and remained above control for 3 days posttreatment. Plasma ET-1 concentration increased from 1.0 ± 0.3 to 1.9 ± 0.4 pg/ml in response to ABT-627 ( day 4) but decreased to control values 4 days posttreatment. These data demonstrate a physiologically important role for endogenous ET-1 and ETA receptors in the long-term regulation of arterial pressure and plasma ET-1 levels in the conscious nonhuman primate.

scholarly journals Identifying the role of group III/IV muscle afferents in the carotid baroreflex control of mean arterial pressure and heart rate during exercise

2018 ◽  
Vol 596 (8) ◽  
pp. 1373-1384 ◽  
Author(s):  
Thomas J. Hureau ◽  
Joshua C. Weavil ◽  
Taylor S. Thurston ◽  
Ryan M. Broxterman ◽  
Ashley D. Nelson ◽  
...  
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Muscle Afferents ◽  
Baroreflex Control ◽  
Group Iii ◽  
Carotid Baroreflex

Role of vasopressin in blood pressure regulation in conscious water-deprived dogs

1983 ◽  
Vol 244 (1) ◽  
pp. R74-R77 ◽  
Author(s):  
J. Schwartz ◽  
I. A. Reid
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Plasma Renin Activity ◽  
Water Deprivation ◽  
Plasma Renin ◽  
Renin Activity ◽  
Pressure Regulation

The role of vasopressin in the regulation of blood pressure during water deprivation was assessed in conscious dogs with two antagonists of the vasoconstrictor activity of vasopressin. In water-replete dogs, vasopressin blockade caused no significant changes in mean arterial pressure, heart rate, plasma renin activity (PRA), or plasma corticosteroid concentration. In the same dogs following 48-h water deprivation, vasopressin blockade increased heart rate from 85 +/- 6 to 134 +/- 15 beats/min (P less than 0.0001), increased cardiac output from 2.0 +/- 0.1 to 3.1 +/- 0.1 1/min (P less than 0.005), and decreased total peripheral resistance from 46.6 +/- 3.1 to 26.9 +/- 3.1 U (P less than 0.001). Plasma renin activity increased from 12.4 +/- 2.2 to 25.9 +/- 3.4 ng ANG I X ml-1 X 3 h-1 (P less than 0.0001) and plasma corticosteroid concentration increased from 3.2 +/- 0.7 to 4.9 +/- 1.2 micrograms/dl (P less than 0.05). Mean arterial pressure did not change significantly. When the same dogs were again deprived of water and pretreated with the beta-adrenoceptor antagonist propranolol, the heart rate and PRA responses to the antagonists were attenuated and mean arterial pressure decreased from 103 +/- 2 to 91 +/- 3 mmHg (P less than 0.001). These data demonstrate that vasopressin plays an important role in blood pressure regulation during water deprivation in conscious dogs.

Role of cardiac output in the pressor responses to graded muscle ischemia in man

1978 ◽  
Vol 45 (4) ◽  
pp. 574-580 ◽  
Author(s):  
F. Bonde-Petersen ◽  
L. B. Rowell ◽  
R. G. Murray ◽  
G. G. Blomqvist ◽  
R. White ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Vascular Conductance ◽  
Total Occlusion ◽  
Muscle Ischemia ◽  
Pressor Responses ◽  
Leg Exercise

Ten men repeatedly performed leg exercise (100–150 W) for 7 min with 30-min recovery periods interspersed. Both legs were made ischemic by total occlusion (OCCL), first for 3 min immediately after exercise and second for 30 s before exercise ended and 3 min into recovery. In addition legs were occluded for 3 min at rest (seated). OCCL at rest increased mean arterial pressure (MAP) by 9 Torr but did not affect cardiac output (CO) or heart rate (HR). OCCL at the end of exercise significantly raised MAP and HR above control values during 3-min recovery but CO was unaffected. OCCL 30 s before the end of exercise further increased MAP and HR significantly during recovery; MAP, CO, and HR were significantly increased above control values (CO by 2.1 1-min-1) during the 3rd min of recovery. We conclude that a strong reflex from ischemic legs maintains normal or elevated CO during leg OCCL. Thus CO was too high relative to total vascular conductance so that MAP was elevated.

Role of the vasoconstrictor and antidiuretic activities of vasopressin in inhibition of renin secretion in conscious dogs

1986 ◽  
Vol 250 (1) ◽  
pp. F92-F96 ◽  
Author(s):  
J. Schwartz ◽  
I. A. Reid
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Plasma Renin Activity ◽  
Arginine Vasopressin ◽  
Plasma Renin ◽  
Renin Secretion ◽  
Conscious Dogs ◽  
Specific Antagonist

The nature of the activity of vasopressin that is responsible for the inhibition of renin secretion was studied in normally hydrated conscious dogs using intravenous infusions of vasopressin and analogues of vasopressin with selective antidiuretic and vasoconstrictor activity. Vasopressin (1.0 ng . kg-1 . min-1) increased mean arterial pressure (MAP) from 106 +/- 2 to 115 +/- 3 mmHg (P less than 0.05) and decreased heart rate (HR) from 81 +/- 6 to 56 +/- 5 beats/min (P less than 0.001). Plasma renin activity (PRA) decreased from 4.4 +/- 1.1 to 2.4 +/- 0.8 ng . ml-1 . 3 h-1 (P less than 0.05). A specific antagonist of the vasoconstrictor activity of vasopressin, d(CH2)5MeTyrAVP (10 micrograms/kg), completely blocked the cardiovascular and renin responses to vasopressin. A selective vasoconstrictor agonist, 2-phenylalanine-8-ornithine oxytocin (1.0 ng . kg-1 . min-1), increased MAP from 112 +/- 4 to 128 +/- 6 mmHg (P less than 0.001) and decreased HR from 69 +/- 3 to 47 +/- 4 beats/min (P less than 0.001). PRA decreased from 5.5 +/- 1.1 to 2.7 +/- 0.2 ng . ml-1 X 3 h-1 (P less than 0.001). In contrast, a selective antidiuretic agonist, 1-deamino-8-D-arginine vasopressin (1.0 ng . kg-1 . min-1) did not alter PRA, MAP, or HR. These results demonstrate that the acute inhibition of renin secretion by vasopressin in normally hydrated conscious dogs is due to vasoconstrictor rather than antidiuretic activity.

scholarly journals Central and peripheral contributors to skeletal muscle hyperemia: response to passive limb movement

2010 ◽  
Vol 108 (1) ◽  
pp. 76-84 ◽  
Author(s):  
John McDaniel ◽  
Anette S. Fjeldstad ◽  
Steve Ives ◽  
Melissa Hayman ◽  
Phil Kithas ◽  
...  
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Stroke Volume ◽  
Limb Movement ◽  
Leg Blood Flow ◽  
Passive Exercise

The central and peripheral contributions to exercise-induced hyperemia are not well understood. Thus, utilizing a reductionist approach, we determined the sequential peripheral and central responses to passive exercise in nine healthy men (33 ± 9 yr). Cardiac output, heart rate, stroke volume, mean arterial pressure, and femoral blood flow of the passively moved leg and stationary (control) leg were evaluated second by second during 3 min of passive knee extension with and without a thigh cuff that occluded leg blood flow. Without the thigh cuff, significant transient increases in cardiac output (1.0 ± 0.6 l/min, Δ15%), heart rate (7 ± 4 beats/min, Δ12%), stroke volume (7 ± 5 ml, Δ7%), passive leg blood flow (411 ± 146 ml/min, Δ151%), and control leg blood flow (125 ± 68 ml/min, Δ43%) and a transient decrease in mean arterial pressure (3 ± 3 mmHg, 4%) occurred shortly after the onset of limb movement. Although the rise and fall rates of these variables differed, they all returned to baseline values within 45 s; therefore, continued limb movement beyond 45 s does not maintain an increase in cardiac output or net blood flow. Similar changes in the central variables occurred when blood flow to the passively moving leg was occluded. These data confirm the role of peripheral factors and reveal an essential supportive role of cardiac output in the hyperemia at the onset of passive limb movement. This cardiac output response provides an important potential link between the physiology of active and passive exercise.

[Nphe1]nociceptin(1–13)-NH2 antagonizes nociceptin-induced hypotension, bradycardia, and hindquarters vasodilation in the anesthetized rat

2002 ◽  
Vol 80 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Y Chen ◽  
M Chang ◽  
Z Z Wang ◽  
L X Chen ◽  
Q Yang ◽  
...  
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Cardiovascular System ◽  
Induced Hypotension ◽  
Selective Antagonist ◽  
Vascular Bed ◽  
Nociceptin Receptor

The purpose of this study was to investigate the effects of [Nphe1]nociceptin(1–13)-NH2 on nociceptin-induced decreases in mean arterial pressure (MAP), heart rate (HR), and hindquarters vascular bed resistance (HVBR) of the anesthetized rat. The results showed that i.c.v. or i.v. [Nphe1]nociceptin(1–13)-NH2 (1.5–12 nmol/kg and 5-120 nmol/kg, respectively) could antagonize the depressor effects of i.c.v. or i.v. nociceptin (3 and 30 nmol/kg, respectively) on MAP and HR. Furthermore, [Nphe1]nociceptin(1–13)-NH2 (5–120 nmol/kg) could reverse nociceptin (30 nmol/kg)-induced decrease of HVBR. However, [Nphe1]nociceptin(1–13)-NH2 had no significant effects on similar effects induced by morphine. Our results suggest that [Nphe1]nociceptin(1–13)-NH2 acts as a selective antagonist of the nociceptin receptor in the cardiovascular system of the rat.Key words: nociceptin, [Nphe1]nociceptin(1–13)-NH2, morphine, mean arterial pressure, heart rate, hindquarters vascular bed resistance.

β-Endorphin, An Endogenous Depressor Agent in the Rat?

1981 ◽  
Vol 61 (s7) ◽  
pp. 339s-342s ◽  
Author(s):  
M. A. Petty ◽  
J. M. A. Sitsen ◽  
W. De Jong
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Subcutaneous Administration ◽  
Nucleus Tractus Solitarii ◽  
Variable Effect ◽  
A Site ◽  
Renal Hypertensive Rats

1. The role of opiates in cardiovascular regulation has been investigated. 2. In urethane-anaesthetized renal hypertensive rats (two-kidney, one-clip Goldblatt model), intracerebroventricular β-endorphin (10 μg) caused a greater fall in mean arterial pressure than in sham-operated controls. 3. Unilateral injection of β-endorphin into the nucleus tractus solitarii of the urethane-anaesthetized rat resulted in a U-shaped dose—response relationship, with a fall in mean arterial pressure and heart rate occurring at low doses. Doses above 10 ng caused a rise in pressure, accompanied by a variable effect on heart rate. 4. The fall in blood pressure and heart rate was prevented by prior subcutaneous administration of naloxone. Naloxone caused an increase in blood pressure when administered alone. 5. These results suggest a depressor role of an endogenous brain opiate, possibly β-endorphin; a site of action is probably the nucleus tractus solitarii.

scholarly journals Central and peripheral hemodynamic responses to passive limb movement: the role of arousal

2012 ◽  
Vol 302 (1) ◽  
pp. H333-H339 ◽  
Author(s):  
Massimo Venturelli ◽  
M. Amann ◽  
J. McDaniel ◽  
J. D. Trinity ◽  
A. S. Fjeldstad ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Stroke Volume ◽  
Visual Feedback ◽  
Passive Movement ◽  
Afferent Feedback ◽  
Hemodynamic Responses

The exact role of arousal in central and peripheral hemodynamic responses to passive limb movement in humans is unclear but has been proposed as a potential contributor. Thus, we used a human model with no lower limb afferent feedback to determine the role of arousal on the hemodynamic response to passive leg movement. In nine people with a spinal cord injury, we compared central and peripheral hemodynamic and ventilatory responses to one-leg passive knee extension with and without visual feedback (M+VF and M-VF, respectively) as well as in a third trial with no movement or visual feedback but the perception of movement (F). Ventilation (V̇e), heart rate, stroke volume, cardiac output, mean arterial pressure, and leg blood flow (LBF) were evaluated during the three protocols. V̇e increased rapidly from baseline in M+VF (55 ± 11%), M-VF (63 ± 13%), and F (48 ± 12%) trials. Central hemodynamics (heart rate, stroke volume, cardiac output, and mean arterial pressure) were unchanged in all trials. LBF increased from baseline by 126 ± 18 ml/min in the M+VF protocol and 109 ± 23 ml/min in the M-VF protocol but was unchanged in the F protocol. Therefore, with the use of model that is devoid of afferent feedback from the legs, the results of this study reveal that, although arousal is invoked by passive movement or the thought of passive movement, as evidenced by the increase in V̇e, there is no central or peripheral hemodynamic impact of this increased neural activity. Additionally, this study revealed that a central hemodynamic response is not an obligatory component of movement-induced LBF.

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

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Martyn Harvey ◽  
Grant Cave ◽  
Daniel Lahner ◽  
Jan Desmet ◽  
Gaynor Prince ◽  
...  
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Beta Blocker ◽  
Lipid Emulsion ◽  
Rabbit Model ◽  
Rate Pressure Product ◽  
High Dose ◽  
Mechanically Ventilated ◽  
Proximal Small Bowel

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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