Arterial pressure response to endothelin-1 and sarafotoxin 6c in rescued endothelin-B-deficient rats

D. M. Pollock, V. Portik-Dobos, C. Procter, C. E. Gariepy, M. Yanagisawa

Research output: Contribution to journalArticle

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Abstract

The spotting lethal rat carries a naturally occurring deletion of the endothelin-B- (ET(B)) receptor gene that prevents expression of functional ET(B)-receptors. Gariepy and colleagues used tissue-specific ET(B) transgene expression to support normal enteric nervous system development. To determine functional consequences of ET(B)-receptor deficiency, studies were conducted to characterize the pressor response to endothelin-1 (ET-1) and the ET(B) agonist, sarafotoxin 6c (S6c) in transgenic rats homozygous for the ET(B)-deficiency (sl/sl). Similar transgenic rats heterozygous for the ET(B) deficiency were used as controls (sl/+). All rats were anesthetized with Inactin (100 mg/kg, i.p.) and a tracheostomy performed. The right carotid artery and right jugular veins were catheterized for measuring mean arterial pressure (MAP) and infusion of peptides, respectively. Following baseline measurement of MAP, hexamethonium was infused (10 mg/kg) to block sympathetic reflex responses. After a 10-15 min stabilization period, ET-1 or S6c was infused at 0.1, 0.3 and 1.0 nmol/kg at 10 min intervals. MAP in the two groups of anesthetized rats was similar during the baseline period. The sl/+ rats showed a classic dose-dependent pressor response to ET-1; a transient vasodilation followed by prolonged vasoconstriction. In contrast, the vasodilation was absent in sl/sl rats. Furthermore, ET-1 was more potent in sl/sl compared to the sl/+ rats. The response to S6c was qualitatively similar to ET-1 in the sl/+ rats. However, the sl/sl rats also had a significant pressor response to the ET(B) agonist, S6c. These studies provide in vivo evidence that the rescued ET(B)-deficient rat lacks functional vasodilatory ET(B) responses in response to ET-1 but retains the vasoconstrictor response to ET(B)-receptor agonists.

Original languageEnglish (US)
JournalJournal of Cardiovascular Pharmacology
Volume36
Issue number5 SUPPL. 1
DOIs
StatePublished - 2000

Fingerprint

Endothelins
Endothelin-1
Arterial Pressure
Endothelin B Receptors
Transgenic Rats
Vasodilation
Enteric Nervous System
sarafotoxins s6
Hexamethonium
Metrorrhagia
Tracheostomy
Jugular Veins
Vasoconstrictor Agents
Vasoconstriction
Transgenes
Carotid Arteries
Reflex
Gene Expression
Peptides

Keywords

  • Endothelin (ET) receptors
  • Endothelin-1 (ET-1)
  • ET(B)-receptors
  • Sarafotoxin 6c (S6c)
  • Transgenic rat

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Arterial pressure response to endothelin-1 and sarafotoxin 6c in rescued endothelin-B-deficient rats. / Pollock, D. M.; Portik-Dobos, V.; Procter, C.; Gariepy, C. E.; Yanagisawa, M.

In: Journal of Cardiovascular Pharmacology, Vol. 36, No. 5 SUPPL. 1, 2000.

Research output: Contribution to journalArticle

Pollock, D. M. ; Portik-Dobos, V. ; Procter, C. ; Gariepy, C. E. ; Yanagisawa, M. / Arterial pressure response to endothelin-1 and sarafotoxin 6c in rescued endothelin-B-deficient rats. In: Journal of Cardiovascular Pharmacology. 2000 ; Vol. 36, No. 5 SUPPL. 1.
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T1 - Arterial pressure response to endothelin-1 and sarafotoxin 6c in rescued endothelin-B-deficient rats

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AU - Portik-Dobos, V.

AU - Procter, C.

AU - Gariepy, C. E.

AU - Yanagisawa, M.

PY - 2000

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AB - The spotting lethal rat carries a naturally occurring deletion of the endothelin-B- (ET(B)) receptor gene that prevents expression of functional ET(B)-receptors. Gariepy and colleagues used tissue-specific ET(B) transgene expression to support normal enteric nervous system development. To determine functional consequences of ET(B)-receptor deficiency, studies were conducted to characterize the pressor response to endothelin-1 (ET-1) and the ET(B) agonist, sarafotoxin 6c (S6c) in transgenic rats homozygous for the ET(B)-deficiency (sl/sl). Similar transgenic rats heterozygous for the ET(B) deficiency were used as controls (sl/+). All rats were anesthetized with Inactin (100 mg/kg, i.p.) and a tracheostomy performed. The right carotid artery and right jugular veins were catheterized for measuring mean arterial pressure (MAP) and infusion of peptides, respectively. Following baseline measurement of MAP, hexamethonium was infused (10 mg/kg) to block sympathetic reflex responses. After a 10-15 min stabilization period, ET-1 or S6c was infused at 0.1, 0.3 and 1.0 nmol/kg at 10 min intervals. MAP in the two groups of anesthetized rats was similar during the baseline period. The sl/+ rats showed a classic dose-dependent pressor response to ET-1; a transient vasodilation followed by prolonged vasoconstriction. In contrast, the vasodilation was absent in sl/sl rats. Furthermore, ET-1 was more potent in sl/sl compared to the sl/+ rats. The response to S6c was qualitatively similar to ET-1 in the sl/+ rats. However, the sl/sl rats also had a significant pressor response to the ET(B) agonist, S6c. These studies provide in vivo evidence that the rescued ET(B)-deficient rat lacks functional vasodilatory ET(B) responses in response to ET-1 but retains the vasoconstrictor response to ET(B)-receptor agonists.

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