Differential effects of endothelin receptor activation on cyclic flow variations in rat mesenteric arteries

Kenichi Fujise, Lowell Stacy, Pamela Beck, Edward T H Yeh, Alice Chuang, Tommy A. Brock, James T. Willerson

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Cyclic flow variations (CFVs) represent repetitive cycles of platelet adherence-aggregation and vasoconstriction, followed by dislodgment of platelet thrombi and restoration of blood flow at the site of vascular injury. Although activation of endothelin A (ETA) and endothelin B (ETB) receptors leads to vasoconstriction and nitric oxide release, respectively, the rules of endogenous endothelin-1 (ET-1) and its receptors in CFVs are unknown. Methods and Results: A side branch of a mesenteric artery of male Wistar rats was cannulated and a short segment of the artery was mechanically injured to induce CFVs. After 20 minutes of saline infusion, either saline (negative control), BQ-123 (ETA receptor antagonist; 10 μg/min), BQ-788 (ETB receptor antagonist, 10 μg/min), or sarafotoxin S6c (ETB receptor agonist, 10 ng/min) was infused for 20 minutes from the side branch into the injured arterial segment. Percent (%) luminal stenosis as well as proximal and distal vessel diameters were observed and quantitatively measured every minute using intravital video microscopy and a micrometer-calibrated video screen. Both BQ-123 and sarafotoxin S6c significantly reduced CFVs represented by the mean luminal stenosis (BQ 123=29 ± 13% and sarafotoxin S6c=27 ± 11% reduction, respectively; P<.05 for both, compared with saline). In contrast, BQ-788 significantly increased CFVs (33 ± 6% increase, P<.05 compared with saline). Moreover, the inhibitory effect of sarafotoxin S6c on CFVs was completely abolished in the presence of N(ω)-nitro-L-arginine methyl ester (L-NAME) (a nitric oxide synthase inhibitor, 10-5 mol/L) in superfusate over the arteries (16.1 ± 5% increase, P=NS compared with saline in the presence of L-NAME). In addition, BQ-123 caused a significant increase in the diameter of the vessel distal to the injured segment (12 ± 4% increase, P<.05 compared with saline). Conclusions: Endogenous ET-1 release from sites of vascular injury contributes to CFVs and vasomotor tone in the rat mesenteric artery CFV model. ETA and ETB receptors have differential roles in CFVs: ETA receptor antagonism and ETB receptor stimulation reduce CFVs, the latter at least partially through increased nitric oxide formation.

Original languageEnglish (US)
Pages (from-to)3641-3646
Number of pages6
JournalCirculation
Volume96
Issue number10
StatePublished - Nov 18 1997
Externally publishedYes

Fingerprint

Endothelin B Receptors
Endothelin Receptors
Mesenteric Arteries
Endothelin A Receptors
Vascular System Injuries
Endothelins
NG-Nitroarginine Methyl Ester
Vasoconstriction
Nitric Oxide
Pathologic Constriction
Arteries
Video Microscopy
Endothelin-1
Platelet Aggregation
Nitric Oxide Synthase
Wistar Rats
Thrombosis
Blood Platelets
cyclo(Trp-Asp-Pro-Val-Leu)
sarafotoxins s6

Keywords

  • Arteries
  • Endothelin
  • Nitric oxide
  • Receptors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Fujise, K., Stacy, L., Beck, P., Yeh, E. T. H., Chuang, A., Brock, T. A., & Willerson, J. T. (1997). Differential effects of endothelin receptor activation on cyclic flow variations in rat mesenteric arteries. Circulation, 96(10), 3641-3646.

Differential effects of endothelin receptor activation on cyclic flow variations in rat mesenteric arteries. / Fujise, Kenichi; Stacy, Lowell; Beck, Pamela; Yeh, Edward T H; Chuang, Alice; Brock, Tommy A.; Willerson, James T.

In: Circulation, Vol. 96, No. 10, 18.11.1997, p. 3641-3646.

Research output: Contribution to journalArticle

Fujise, K, Stacy, L, Beck, P, Yeh, ETH, Chuang, A, Brock, TA & Willerson, JT 1997, 'Differential effects of endothelin receptor activation on cyclic flow variations in rat mesenteric arteries', Circulation, vol. 96, no. 10, pp. 3641-3646.
Fujise K, Stacy L, Beck P, Yeh ETH, Chuang A, Brock TA et al. Differential effects of endothelin receptor activation on cyclic flow variations in rat mesenteric arteries. Circulation. 1997 Nov 18;96(10):3641-3646.
Fujise, Kenichi ; Stacy, Lowell ; Beck, Pamela ; Yeh, Edward T H ; Chuang, Alice ; Brock, Tommy A. ; Willerson, James T. / Differential effects of endothelin receptor activation on cyclic flow variations in rat mesenteric arteries. In: Circulation. 1997 ; Vol. 96, No. 10. pp. 3641-3646.
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abstract = "Background: Cyclic flow variations (CFVs) represent repetitive cycles of platelet adherence-aggregation and vasoconstriction, followed by dislodgment of platelet thrombi and restoration of blood flow at the site of vascular injury. Although activation of endothelin A (ETA) and endothelin B (ETB) receptors leads to vasoconstriction and nitric oxide release, respectively, the rules of endogenous endothelin-1 (ET-1) and its receptors in CFVs are unknown. Methods and Results: A side branch of a mesenteric artery of male Wistar rats was cannulated and a short segment of the artery was mechanically injured to induce CFVs. After 20 minutes of saline infusion, either saline (negative control), BQ-123 (ETA receptor antagonist; 10 μg/min), BQ-788 (ETB receptor antagonist, 10 μg/min), or sarafotoxin S6c (ETB receptor agonist, 10 ng/min) was infused for 20 minutes from the side branch into the injured arterial segment. Percent ({\%}) luminal stenosis as well as proximal and distal vessel diameters were observed and quantitatively measured every minute using intravital video microscopy and a micrometer-calibrated video screen. Both BQ-123 and sarafotoxin S6c significantly reduced CFVs represented by the mean luminal stenosis (BQ 123=29 ± 13{\%} and sarafotoxin S6c=27 ± 11{\%} reduction, respectively; P<.05 for both, compared with saline). In contrast, BQ-788 significantly increased CFVs (33 ± 6{\%} increase, P<.05 compared with saline). Moreover, the inhibitory effect of sarafotoxin S6c on CFVs was completely abolished in the presence of N(ω)-nitro-L-arginine methyl ester (L-NAME) (a nitric oxide synthase inhibitor, 10-5 mol/L) in superfusate over the arteries (16.1 ± 5{\%} increase, P=NS compared with saline in the presence of L-NAME). In addition, BQ-123 caused a significant increase in the diameter of the vessel distal to the injured segment (12 ± 4{\%} increase, P<.05 compared with saline). Conclusions: Endogenous ET-1 release from sites of vascular injury contributes to CFVs and vasomotor tone in the rat mesenteric artery CFV model. ETA and ETB receptors have differential roles in CFVs: ETA receptor antagonism and ETB receptor stimulation reduce CFVs, the latter at least partially through increased nitric oxide formation.",
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T1 - Differential effects of endothelin receptor activation on cyclic flow variations in rat mesenteric arteries

AU - Fujise, Kenichi

AU - Stacy, Lowell

AU - Beck, Pamela

AU - Yeh, Edward T H

AU - Chuang, Alice

AU - Brock, Tommy A.

AU - Willerson, James T.

PY - 1997/11/18

Y1 - 1997/11/18

N2 - Background: Cyclic flow variations (CFVs) represent repetitive cycles of platelet adherence-aggregation and vasoconstriction, followed by dislodgment of platelet thrombi and restoration of blood flow at the site of vascular injury. Although activation of endothelin A (ETA) and endothelin B (ETB) receptors leads to vasoconstriction and nitric oxide release, respectively, the rules of endogenous endothelin-1 (ET-1) and its receptors in CFVs are unknown. Methods and Results: A side branch of a mesenteric artery of male Wistar rats was cannulated and a short segment of the artery was mechanically injured to induce CFVs. After 20 minutes of saline infusion, either saline (negative control), BQ-123 (ETA receptor antagonist; 10 μg/min), BQ-788 (ETB receptor antagonist, 10 μg/min), or sarafotoxin S6c (ETB receptor agonist, 10 ng/min) was infused for 20 minutes from the side branch into the injured arterial segment. Percent (%) luminal stenosis as well as proximal and distal vessel diameters were observed and quantitatively measured every minute using intravital video microscopy and a micrometer-calibrated video screen. Both BQ-123 and sarafotoxin S6c significantly reduced CFVs represented by the mean luminal stenosis (BQ 123=29 ± 13% and sarafotoxin S6c=27 ± 11% reduction, respectively; P<.05 for both, compared with saline). In contrast, BQ-788 significantly increased CFVs (33 ± 6% increase, P<.05 compared with saline). Moreover, the inhibitory effect of sarafotoxin S6c on CFVs was completely abolished in the presence of N(ω)-nitro-L-arginine methyl ester (L-NAME) (a nitric oxide synthase inhibitor, 10-5 mol/L) in superfusate over the arteries (16.1 ± 5% increase, P=NS compared with saline in the presence of L-NAME). In addition, BQ-123 caused a significant increase in the diameter of the vessel distal to the injured segment (12 ± 4% increase, P<.05 compared with saline). Conclusions: Endogenous ET-1 release from sites of vascular injury contributes to CFVs and vasomotor tone in the rat mesenteric artery CFV model. ETA and ETB receptors have differential roles in CFVs: ETA receptor antagonism and ETB receptor stimulation reduce CFVs, the latter at least partially through increased nitric oxide formation.

AB - Background: Cyclic flow variations (CFVs) represent repetitive cycles of platelet adherence-aggregation and vasoconstriction, followed by dislodgment of platelet thrombi and restoration of blood flow at the site of vascular injury. Although activation of endothelin A (ETA) and endothelin B (ETB) receptors leads to vasoconstriction and nitric oxide release, respectively, the rules of endogenous endothelin-1 (ET-1) and its receptors in CFVs are unknown. Methods and Results: A side branch of a mesenteric artery of male Wistar rats was cannulated and a short segment of the artery was mechanically injured to induce CFVs. After 20 minutes of saline infusion, either saline (negative control), BQ-123 (ETA receptor antagonist; 10 μg/min), BQ-788 (ETB receptor antagonist, 10 μg/min), or sarafotoxin S6c (ETB receptor agonist, 10 ng/min) was infused for 20 minutes from the side branch into the injured arterial segment. Percent (%) luminal stenosis as well as proximal and distal vessel diameters were observed and quantitatively measured every minute using intravital video microscopy and a micrometer-calibrated video screen. Both BQ-123 and sarafotoxin S6c significantly reduced CFVs represented by the mean luminal stenosis (BQ 123=29 ± 13% and sarafotoxin S6c=27 ± 11% reduction, respectively; P<.05 for both, compared with saline). In contrast, BQ-788 significantly increased CFVs (33 ± 6% increase, P<.05 compared with saline). Moreover, the inhibitory effect of sarafotoxin S6c on CFVs was completely abolished in the presence of N(ω)-nitro-L-arginine methyl ester (L-NAME) (a nitric oxide synthase inhibitor, 10-5 mol/L) in superfusate over the arteries (16.1 ± 5% increase, P=NS compared with saline in the presence of L-NAME). In addition, BQ-123 caused a significant increase in the diameter of the vessel distal to the injured segment (12 ± 4% increase, P<.05 compared with saline). Conclusions: Endogenous ET-1 release from sites of vascular injury contributes to CFVs and vasomotor tone in the rat mesenteric artery CFV model. ETA and ETB receptors have differential roles in CFVs: ETA receptor antagonism and ETB receptor stimulation reduce CFVs, the latter at least partially through increased nitric oxide formation.

KW - Arteries

KW - Endothelin

KW - Nitric oxide

KW - Receptors

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