Comparison between the vasoactive actions of endothelin and arginine vasopressin in pithed rats after pretreatment with BAY K 8644, nifedipine or pertussis toxin

R. Tabrizchi, Christopher Triggle

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Both human endothelin 1 (ET1) and rat endothelin 3 (ET3) produced dose-dependent pressor effects in the pithed rat. The pressor actions of ET3 and arginine vasopressin (AVP) were compared with one another in pithed rats in the presence of the calcium channel activator BAY K 8644 or the calcium channel antagonist nifedipine i.a. and also after pretreatment with pertussis toxin i.v. The diastolic pressure recorded in animals treated with the vehicle was 41 ± 1 mm Hg, and administration of BAY K 8644 increased the diastolic pressure to 53 ± 3 mm Hg, whereas nifedipine caused a decrease in diastolic pressure to 33 ± 2 mm Hg. AVP, ET1 and ET3 dose-dependently increased diastolic blood pressure, with AVP being the most potent and producing the greatest total increase in pressure. ET1 was more potent than ET3; however, the maximal increases produced by the endothelins were identical. The actions of ET3 but not AVP were potentiated in the presence of BAY K 8644. Furthermore, nifedipine significantly impaired responses induced by endothelin but not those produced by AVP. It was observed that animals treated with pertussis toxin 3 days before the conduction of the experiments had a significantly lower diastolic blood pressure as compared with saline-treated animals. Treatment with pertussis toxin caused the dose-diastolic pressure response curve to ET to be displaced to the right, whereas the dose-diastolic pressure response to AVP was not affected. These rsults indicate that a nifedipine-sensitive, presumably extracellular, calcium pool is partly responsible for the pressor response induced by ET, whereas the response to AVP appears to depend upon activation of a nifedipine-insensitive, presumably intracellular, source of calcium. Furthermore, it can be suggested that, in vascular smooth muscle, ET activates a pertussis toxin-sensitive G-protein that is coupled to a receptor-operated calcium or nonspecific cation channel, whereas responses induced by AVP do not appear to be mediated through a G-protein that is sensitive to pertussis toxin.

Original languageEnglish
Pages (from-to)272-276
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume253
Issue number1
Publication statusPublished - 1990
Externally publishedYes

Fingerprint

Arginine Vasopressin
Endothelins
Pertussis Toxin
Nifedipine
Endothelin-3
Blood Pressure
Endothelin-1
GTP-Binding Proteins
Calcium Channel Agonists
Calcium
Calcium-Sensing Receptors
Calcium Channel Blockers
Vascular Smooth Muscle
Cations
Pressure

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

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title = "Comparison between the vasoactive actions of endothelin and arginine vasopressin in pithed rats after pretreatment with BAY K 8644, nifedipine or pertussis toxin",
abstract = "Both human endothelin 1 (ET1) and rat endothelin 3 (ET3) produced dose-dependent pressor effects in the pithed rat. The pressor actions of ET3 and arginine vasopressin (AVP) were compared with one another in pithed rats in the presence of the calcium channel activator BAY K 8644 or the calcium channel antagonist nifedipine i.a. and also after pretreatment with pertussis toxin i.v. The diastolic pressure recorded in animals treated with the vehicle was 41 ± 1 mm Hg, and administration of BAY K 8644 increased the diastolic pressure to 53 ± 3 mm Hg, whereas nifedipine caused a decrease in diastolic pressure to 33 ± 2 mm Hg. AVP, ET1 and ET3 dose-dependently increased diastolic blood pressure, with AVP being the most potent and producing the greatest total increase in pressure. ET1 was more potent than ET3; however, the maximal increases produced by the endothelins were identical. The actions of ET3 but not AVP were potentiated in the presence of BAY K 8644. Furthermore, nifedipine significantly impaired responses induced by endothelin but not those produced by AVP. It was observed that animals treated with pertussis toxin 3 days before the conduction of the experiments had a significantly lower diastolic blood pressure as compared with saline-treated animals. Treatment with pertussis toxin caused the dose-diastolic pressure response curve to ET to be displaced to the right, whereas the dose-diastolic pressure response to AVP was not affected. These rsults indicate that a nifedipine-sensitive, presumably extracellular, calcium pool is partly responsible for the pressor response induced by ET, whereas the response to AVP appears to depend upon activation of a nifedipine-insensitive, presumably intracellular, source of calcium. Furthermore, it can be suggested that, in vascular smooth muscle, ET activates a pertussis toxin-sensitive G-protein that is coupled to a receptor-operated calcium or nonspecific cation channel, whereas responses induced by AVP do not appear to be mediated through a G-protein that is sensitive to pertussis toxin.",
author = "R. Tabrizchi and Christopher Triggle",
year = "1990",
language = "English",
volume = "253",
pages = "272--276",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
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AU - Triggle, Christopher

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N2 - Both human endothelin 1 (ET1) and rat endothelin 3 (ET3) produced dose-dependent pressor effects in the pithed rat. The pressor actions of ET3 and arginine vasopressin (AVP) were compared with one another in pithed rats in the presence of the calcium channel activator BAY K 8644 or the calcium channel antagonist nifedipine i.a. and also after pretreatment with pertussis toxin i.v. The diastolic pressure recorded in animals treated with the vehicle was 41 ± 1 mm Hg, and administration of BAY K 8644 increased the diastolic pressure to 53 ± 3 mm Hg, whereas nifedipine caused a decrease in diastolic pressure to 33 ± 2 mm Hg. AVP, ET1 and ET3 dose-dependently increased diastolic blood pressure, with AVP being the most potent and producing the greatest total increase in pressure. ET1 was more potent than ET3; however, the maximal increases produced by the endothelins were identical. The actions of ET3 but not AVP were potentiated in the presence of BAY K 8644. Furthermore, nifedipine significantly impaired responses induced by endothelin but not those produced by AVP. It was observed that animals treated with pertussis toxin 3 days before the conduction of the experiments had a significantly lower diastolic blood pressure as compared with saline-treated animals. Treatment with pertussis toxin caused the dose-diastolic pressure response curve to ET to be displaced to the right, whereas the dose-diastolic pressure response to AVP was not affected. These rsults indicate that a nifedipine-sensitive, presumably extracellular, calcium pool is partly responsible for the pressor response induced by ET, whereas the response to AVP appears to depend upon activation of a nifedipine-insensitive, presumably intracellular, source of calcium. Furthermore, it can be suggested that, in vascular smooth muscle, ET activates a pertussis toxin-sensitive G-protein that is coupled to a receptor-operated calcium or nonspecific cation channel, whereas responses induced by AVP do not appear to be mediated through a G-protein that is sensitive to pertussis toxin.

AB - Both human endothelin 1 (ET1) and rat endothelin 3 (ET3) produced dose-dependent pressor effects in the pithed rat. The pressor actions of ET3 and arginine vasopressin (AVP) were compared with one another in pithed rats in the presence of the calcium channel activator BAY K 8644 or the calcium channel antagonist nifedipine i.a. and also after pretreatment with pertussis toxin i.v. The diastolic pressure recorded in animals treated with the vehicle was 41 ± 1 mm Hg, and administration of BAY K 8644 increased the diastolic pressure to 53 ± 3 mm Hg, whereas nifedipine caused a decrease in diastolic pressure to 33 ± 2 mm Hg. AVP, ET1 and ET3 dose-dependently increased diastolic blood pressure, with AVP being the most potent and producing the greatest total increase in pressure. ET1 was more potent than ET3; however, the maximal increases produced by the endothelins were identical. The actions of ET3 but not AVP were potentiated in the presence of BAY K 8644. Furthermore, nifedipine significantly impaired responses induced by endothelin but not those produced by AVP. It was observed that animals treated with pertussis toxin 3 days before the conduction of the experiments had a significantly lower diastolic blood pressure as compared with saline-treated animals. Treatment with pertussis toxin caused the dose-diastolic pressure response curve to ET to be displaced to the right, whereas the dose-diastolic pressure response to AVP was not affected. These rsults indicate that a nifedipine-sensitive, presumably extracellular, calcium pool is partly responsible for the pressor response induced by ET, whereas the response to AVP appears to depend upon activation of a nifedipine-insensitive, presumably intracellular, source of calcium. Furthermore, it can be suggested that, in vascular smooth muscle, ET activates a pertussis toxin-sensitive G-protein that is coupled to a receptor-operated calcium or nonspecific cation channel, whereas responses induced by AVP do not appear to be mediated through a G-protein that is sensitive to pertussis toxin.

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