Selepressin and Arginine Vasopressin Do Not Display Cardiovascular Risk in Atherosclerotic Rabbit.

Boucheix O, Blakytny R, Haroutunian G, Henriksson M, Laporte R, Milano S, Reinheimer TM

PloS one27 Oct 2016Cited by 4 (Europe PMC)

PMID27788216PMCIDPMC5082805DOI10.1371/journal.pone.0165422PepBankPUB-27788216

Summary

BackgroundSeptic shock remains associated with significant mortality rates. Arginine vasopressin (AVP) and analogs with V1A receptor agonist activity are increasingly used to treat fluid-resistant vasodilatory hypotension, including catecholamine-refractory septic shock. Clinical studies have been restricted to healthy volunteers and catecholamine-refractory septic shock patients excluding subjects with cardiac co-morbidities because of presumed safety issues. The novel selective V1A receptor agonist selepressin, with short half-life, has been designed to avoid V2 receptor-related complications and long-term V1A receptor activation. Cardiovascular safety of selepressin, AVP, and the septic shock standard of care norepinephrine was investigated in a rabbit model of early-stage atherosclerosis.MethodsAtherosclerosis was established in New Zealand White rabbits using a 1% cholesterol-containing diet. Selepressin, AVP, or norepinephrine was administered as cumulative intravenous infusion rates to atherosclerotic and non-atherosclerotic animals.ResultsSelepressin and AVP induced a slight dose-dependent increase in arterial pressure (AP) associated with a moderate decrease in heart rate, no change in stroke volume, and a moderate decrease in aortic blood flow (ABF). In contrast, norepinephrine induced a marked dose-dependent increase in AP associated with a lesser decrease in the heart rate, an increase in stroke volume, and a moderate increase in ABF. For all three vasopressors, there was no difference in responses between atherosclerotic and non-atherosclerotic animals.ConclusionFurther studies should be considered using more advanced atherosclerosis models, including with septic shock, before considering septic shock clinical trials of patients with comorbidities. Here, selepressin and AVP treatments did not display relevant cardiovascular risk in early-stage rabbit atherosclerosis.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

8 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Safety outcome
In rabbits with and without early-stage atherosclerosis, selepressin induced a slight dose-dependent increase in arterial pressure.
In plain wordsIn rabbits with and without early atherosclerosis, selepressin slightly increased blood pressure in a dose-dependent manner.
Peptide
Selepressin
Outcome
IncreaseArterial pressure
Study
rabbitn: not reported in source
New Zealand White rabbits with and without early-stage diet-induced atherosclerosis
Outcome group
Blood pressure · Cardiovascular
Studied dose
Dose not stated · intravenous infusionAs given in this study (rabbit).
Source sentences
Summary
Selepressin and AVP induced a slight dose-dependent increase in arterial pressure (AP) associated with a moderate decrease in heart rate, no change in stroke volume, and a moderate decrease in aortic blood flow (ABF).
3 context sentences(design, population, supporting numbers)
Summary · context
Cardiovascular safety of selepressin, AVP, and the septic shock standard of care norepinephrine was investigated in a rabbit model of early-stage atherosclerosis.
Summary · context
Atherosclerosis was established in New Zealand White rabbits using a 1% cholesterol-containing diet.
Summary · context
Selepressin, AVP, or norepinephrine was administered as cumulative intravenous infusion rates to atherosclerotic and non-atherosclerotic animals.
Show in the study text Report a problemFND-2778821601
02AnimalAnimal study (in vivo)Safety outcome
In rabbits with and without early-stage atherosclerosis, selepressin moderately decreased heart rate.
In plain wordsIn rabbits with and without early atherosclerosis, selepressin moderately decreased heart rate.
Peptide
Selepressin
Outcome
DecreaseHeart rate
Study
rabbitn: not reported in source
New Zealand White rabbits with and without early-stage diet-induced atherosclerosis
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated · intravenous infusionAs given in this study (rabbit).
Source sentences
Summary
Selepressin and AVP induced a slight dose-dependent increase in arterial pressure (AP) associated with a moderate decrease in heart rate, no change in stroke volume, and a moderate decrease in aortic blood flow (ABF).
3 context sentences(design, population, supporting numbers)
Summary · context
Cardiovascular safety of selepressin, AVP, and the septic shock standard of care norepinephrine was investigated in a rabbit model of early-stage atherosclerosis.
Summary · context
Atherosclerosis was established in New Zealand White rabbits using a 1% cholesterol-containing diet.
Summary · context
Selepressin, AVP, or norepinephrine was administered as cumulative intravenous infusion rates to atherosclerotic and non-atherosclerotic animals.
Show in the study text Report a problemFND-2778821602
03AnimalAnimal study (in vivo)Safety outcome
In rabbits with and without early-stage atherosclerosis, selepressin did not change stroke volume.
In plain wordsIn rabbits with and without early atherosclerosis, selepressin did not change the blood volume pumped per heartbeat.
Peptide
Selepressin
Outcome
No significant changeStroke volume
Study
rabbitn: not reported in source
New Zealand White rabbits with and without early-stage diet-induced atherosclerosis
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated · intravenous infusionAs given in this study (rabbit).
Source sentences
Summary
Selepressin and AVP induced a slight dose-dependent increase in arterial pressure (AP) associated with a moderate decrease in heart rate, no change in stroke volume, and a moderate decrease in aortic blood flow (ABF).
3 context sentences(design, population, supporting numbers)
Summary · context
Cardiovascular safety of selepressin, AVP, and the septic shock standard of care norepinephrine was investigated in a rabbit model of early-stage atherosclerosis.
Summary · context
Atherosclerosis was established in New Zealand White rabbits using a 1% cholesterol-containing diet.
Summary · context
Selepressin, AVP, or norepinephrine was administered as cumulative intravenous infusion rates to atherosclerotic and non-atherosclerotic animals.
Show in the study text Report a problemFND-2778821603
04AnimalAnimal study (in vivo)Safety outcome
In rabbits with and without early-stage atherosclerosis, selepressin moderately decreased aortic blood flow.
In plain wordsIn rabbits with and without early atherosclerosis, selepressin moderately decreased aortic blood flow.
Peptide
Selepressin
Outcome
DecreaseAortic blood flow
Study
rabbitn: not reported in source
New Zealand White rabbits with and without early-stage diet-induced atherosclerosis
Outcome group
Vascular function · Cardiovascular
Studied dose
Dose not stated · intravenous infusionAs given in this study (rabbit).
Source sentences
Summary
Selepressin and AVP induced a slight dose-dependent increase in arterial pressure (AP) associated with a moderate decrease in heart rate, no change in stroke volume, and a moderate decrease in aortic blood flow (ABF).
3 context sentences(design, population, supporting numbers)
Summary · context
Cardiovascular safety of selepressin, AVP, and the septic shock standard of care norepinephrine was investigated in a rabbit model of early-stage atherosclerosis.
Summary · context
Atherosclerosis was established in New Zealand White rabbits using a 1% cholesterol-containing diet.
Summary · context
Selepressin, AVP, or norepinephrine was administered as cumulative intravenous infusion rates to atherosclerotic and non-atherosclerotic animals.
Show in the study text Report a problemFND-2778821604
05AnimalAnimal study (in vivo)Safety outcome
In rabbits, selepressin arterial pressure responses did not differ between atherosclerotic and non-atherosclerotic animals.
In plain wordsIn rabbits, selepressin blood pressure responses did not differ between animals with and without atherosclerosis.
Peptide
Selepressin
Outcome
No significant changeArterial pressure response by atherosclerosis status
Study
rabbitn: not reported in source
New Zealand White rabbits with and without early-stage diet-induced atherosclerosis
Comparator
Non-atherosclerotic rabbits
Outcome group
Blood pressure · Cardiovascular
Studied dose
Dose not stated · intravenous infusionAs given in this study (rabbit).
Source sentences
Summary
For all three vasopressors, there was no difference in responses between atherosclerotic and non-atherosclerotic animals.
4 context sentences(design, population, supporting numbers)
Summary · context
Selepressin and AVP induced a slight dose-dependent increase in arterial pressure (AP) associated with a moderate decrease in heart rate, no change in stroke volume, and a moderate decrease in aortic blood flow (ABF).
Summary · context
Cardiovascular safety of selepressin, AVP, and the septic shock standard of care norepinephrine was investigated in a rabbit model of early-stage atherosclerosis.
Summary · context
Atherosclerosis was established in New Zealand White rabbits using a 1% cholesterol-containing diet.
Summary · context
Selepressin, AVP, or norepinephrine was administered as cumulative intravenous infusion rates to atherosclerotic and non-atherosclerotic animals.
Show in the study text Report a problemFND-2778821605
06AnimalAnimal study (in vivo)Safety outcome
In rabbits, selepressin heart rate responses did not differ between atherosclerotic and non-atherosclerotic animals.
In plain wordsIn rabbits, selepressin heart rate responses did not differ between animals with and without atherosclerosis.
Peptide
Selepressin
Outcome
No significant changeHeart rate response by atherosclerosis status
Study
rabbitn: not reported in source
New Zealand White rabbits with and without early-stage diet-induced atherosclerosis
Comparator
Non-atherosclerotic rabbits
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated · intravenous infusionAs given in this study (rabbit).
Source sentences
Summary
For all three vasopressors, there was no difference in responses between atherosclerotic and non-atherosclerotic animals.
4 context sentences(design, population, supporting numbers)
Summary · context
Selepressin and AVP induced a slight dose-dependent increase in arterial pressure (AP) associated with a moderate decrease in heart rate, no change in stroke volume, and a moderate decrease in aortic blood flow (ABF).
Summary · context
Cardiovascular safety of selepressin, AVP, and the septic shock standard of care norepinephrine was investigated in a rabbit model of early-stage atherosclerosis.
Summary · context
Atherosclerosis was established in New Zealand White rabbits using a 1% cholesterol-containing diet.
Summary · context
Selepressin, AVP, or norepinephrine was administered as cumulative intravenous infusion rates to atherosclerotic and non-atherosclerotic animals.
Show in the study text Report a problemFND-2778821606
07AnimalAnimal study (in vivo)Safety outcome
In rabbits, selepressin stroke volume responses did not differ between atherosclerotic and non-atherosclerotic animals.
In plain wordsIn rabbits, selepressin responses in blood volume per heartbeat did not differ between animals with and without atherosclerosis.
Peptide
Selepressin
Outcome
No significant changeStroke volume response by atherosclerosis status
Study
rabbitn: not reported in source
New Zealand White rabbits with and without early-stage diet-induced atherosclerosis
Comparator
Non-atherosclerotic rabbits
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated · intravenous infusionAs given in this study (rabbit).
Source sentences
Summary
For all three vasopressors, there was no difference in responses between atherosclerotic and non-atherosclerotic animals.
4 context sentences(design, population, supporting numbers)
Summary · context
Selepressin and AVP induced a slight dose-dependent increase in arterial pressure (AP) associated with a moderate decrease in heart rate, no change in stroke volume, and a moderate decrease in aortic blood flow (ABF).
Summary · context
Cardiovascular safety of selepressin, AVP, and the septic shock standard of care norepinephrine was investigated in a rabbit model of early-stage atherosclerosis.
Summary · context
Atherosclerosis was established in New Zealand White rabbits using a 1% cholesterol-containing diet.
Summary · context
Selepressin, AVP, or norepinephrine was administered as cumulative intravenous infusion rates to atherosclerotic and non-atherosclerotic animals.
Show in the study text Report a problemFND-2778821607
08AnimalAnimal study (in vivo)Safety outcome
In rabbits, selepressin aortic blood flow responses did not differ between atherosclerotic and non-atherosclerotic animals.
In plain wordsIn rabbits, selepressin aortic blood flow responses did not differ between animals with and without atherosclerosis.
Peptide
Selepressin
Outcome
No significant changeAortic blood flow response by atherosclerosis status
Study
rabbitn: not reported in source
New Zealand White rabbits with and without early-stage diet-induced atherosclerosis
Comparator
Non-atherosclerotic rabbits
Outcome group
Vascular function · Cardiovascular
Studied dose
Dose not stated · intravenous infusionAs given in this study (rabbit).
Source sentences
Summary
For all three vasopressors, there was no difference in responses between atherosclerotic and non-atherosclerotic animals.
4 context sentences(design, population, supporting numbers)
Summary · context
Selepressin and AVP induced a slight dose-dependent increase in arterial pressure (AP) associated with a moderate decrease in heart rate, no change in stroke volume, and a moderate decrease in aortic blood flow (ABF).
Summary · context
Cardiovascular safety of selepressin, AVP, and the septic shock standard of care norepinephrine was investigated in a rabbit model of early-stage atherosclerosis.
Summary · context
Atherosclerosis was established in New Zealand White rabbits using a 1% cholesterol-containing diet.
Summary · context
Selepressin, AVP, or norepinephrine was administered as cumulative intravenous infusion rates to atherosclerotic and non-atherosclerotic animals.
Show in the study text Report a problemFND-2778821608

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

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Version 2Current
27 Oct 2026, 18:20 UTC
Study results updated
Version 1
27 Oct 2026, 16:32 UTC
First added · source update from Europe PMC

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