Effects of pertussis and cholera toxins on α-adrenoceptor function in rat tail artery

Differences in hypertension

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The α1- and α2-adrenoceptor-stimulated contractile responses of rat tail artery rings were compared in Sprague-Dawley (SD), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY) rats that were untreated, treated with pertussis toxin, or treated with cholera toxin. The maximal responses, expressed as milligrams of tension, induced by clonidine (an α2-adrenoceptor agonist) and cirazoline (a selective α1-adrenoceptor agonist) were significantly greater in SHR than in SD or WKY, and the tissues were more sensitive to the agonists in SHR or SD than in WKY. Yohimbine (0.1 μM), a selective α2-adrenoceptor antagonist, shifted the dose-response curves for clonidine to the right. The effects of yohimbine were greater in SD than in WKY or SHR, but not different between WKY and SHR. Prazosin (0.05 μM), a selective α1-adrenoceptor antagonist, shifted the dose-response curves of cirazoline to the right, but the effects of prazosin were not different among these three strains of rats. Nifedipine (0.05 μM) completely blocked the response to clonidine in SD and WKY; however,in SHR, approximately one-third of the response to clonidine was resistant to nifedipine. Nifedipine, at 0.05 μM, only partially inhibited responses to cirazoline in SD, SHR, and WKY, and no differences were noted between the strains. Pertussis toxin pretreatment (50 μg/kg, 3 days before experiment) almost completely blocked the responses to clonidine, but only partially inhibited those to cirazoline. After pertussis toxin pretreatment, the responses (maximal effects and EC50s) to clonidine and cirazoline were not significantly different in arteries from the three strains of rats. A combination of pertussis toxin and nifedipine resulted in an additive inhibition of the responses induced by cirazoline. cholera toxin pretreatment (0.3 mg/kg, 3 days before experiment), however, had no effects on the contractile responses induced by either clonidine or cirazoline, or on the inhibitory effects of nifedipine in SHR, SD, and WKY. These results indicate that (i) the maximal responses to α1- and α2-adrenoceptor agonists are enhanced in rat tail artery rings from SHR; (ii) tissues from SH and SD rats are also more sensitive to cirazoline and clonidine than are tissues from WKY: (iii) responses to clonidine, but not cirazoline, in tissues from the SHR are less sensitive to nifedipine than tissues from SD and WKY; (iv) a G-protein sensitive to pertussis but not cholera toxin is involved in the regulation of both α1- and α2-adrenoceptor signal transduction processes in rat tail artery smooth muscle; and (v) pretreatment with pertussis toxin reduces the enhanced response levels of SHR tissues so that the maximal contractile responses to both α1- and α2-adrenoceptor agonists are equivalent in arteries from the three strains of rats.

Original languageEnglish
Pages (from-to)791-799
Number of pages9
JournalCanadian Journal of Physiology and Pharmacology
Volume71
Issue number10-11
Publication statusPublished - 1993
Externally publishedYes

Fingerprint

Cholera Toxin
Pertussis Toxin
Clonidine
Adrenergic Receptors
Tail
Arteries
Nifedipine
Hypertension
Yohimbine
Prazosin
cirazoline
Inbred WKY Rats
Whooping Cough
GTP-Binding Proteins
Smooth Muscle
Sprague Dawley Rats
Signal Transduction

Keywords

  • α-adrenoceptor
  • α-adrenoceptor
  • cholera toxin
  • pertussis toxin
  • rat tail artery ring

ASJC Scopus subject areas

  • Physiology
  • Pharmacology

Cite this

@article{f7440e56187244c9957384cc4cadb1ce,
title = "Effects of pertussis and cholera toxins on α-adrenoceptor function in rat tail artery: Differences in hypertension",
abstract = "The α1- and α2-adrenoceptor-stimulated contractile responses of rat tail artery rings were compared in Sprague-Dawley (SD), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY) rats that were untreated, treated with pertussis toxin, or treated with cholera toxin. The maximal responses, expressed as milligrams of tension, induced by clonidine (an α2-adrenoceptor agonist) and cirazoline (a selective α1-adrenoceptor agonist) were significantly greater in SHR than in SD or WKY, and the tissues were more sensitive to the agonists in SHR or SD than in WKY. Yohimbine (0.1 μM), a selective α2-adrenoceptor antagonist, shifted the dose-response curves for clonidine to the right. The effects of yohimbine were greater in SD than in WKY or SHR, but not different between WKY and SHR. Prazosin (0.05 μM), a selective α1-adrenoceptor antagonist, shifted the dose-response curves of cirazoline to the right, but the effects of prazosin were not different among these three strains of rats. Nifedipine (0.05 μM) completely blocked the response to clonidine in SD and WKY; however,in SHR, approximately one-third of the response to clonidine was resistant to nifedipine. Nifedipine, at 0.05 μM, only partially inhibited responses to cirazoline in SD, SHR, and WKY, and no differences were noted between the strains. Pertussis toxin pretreatment (50 μg/kg, 3 days before experiment) almost completely blocked the responses to clonidine, but only partially inhibited those to cirazoline. After pertussis toxin pretreatment, the responses (maximal effects and EC50s) to clonidine and cirazoline were not significantly different in arteries from the three strains of rats. A combination of pertussis toxin and nifedipine resulted in an additive inhibition of the responses induced by cirazoline. cholera toxin pretreatment (0.3 mg/kg, 3 days before experiment), however, had no effects on the contractile responses induced by either clonidine or cirazoline, or on the inhibitory effects of nifedipine in SHR, SD, and WKY. These results indicate that (i) the maximal responses to α1- and α2-adrenoceptor agonists are enhanced in rat tail artery rings from SHR; (ii) tissues from SH and SD rats are also more sensitive to cirazoline and clonidine than are tissues from WKY: (iii) responses to clonidine, but not cirazoline, in tissues from the SHR are less sensitive to nifedipine than tissues from SD and WKY; (iv) a G-protein sensitive to pertussis but not cholera toxin is involved in the regulation of both α1- and α2-adrenoceptor signal transduction processes in rat tail artery smooth muscle; and (v) pretreatment with pertussis toxin reduces the enhanced response levels of SHR tissues so that the maximal contractile responses to both α1- and α2-adrenoceptor agonists are equivalent in arteries from the three strains of rats.",
keywords = "α-adrenoceptor, α-adrenoceptor, cholera toxin, pertussis toxin, rat tail artery ring",
author = "Li, {X. F.} and Christopher Triggle",
year = "1993",
language = "English",
volume = "71",
pages = "791--799",
journal = "Canadian Journal of Physiology and Pharmacology",
issn = "0008-4212",
publisher = "National Research Council of Canada",
number = "10-11",

}

TY - JOUR

T1 - Effects of pertussis and cholera toxins on α-adrenoceptor function in rat tail artery

T2 - Differences in hypertension

AU - Li, X. F.

AU - Triggle, Christopher

PY - 1993

Y1 - 1993

N2 - The α1- and α2-adrenoceptor-stimulated contractile responses of rat tail artery rings were compared in Sprague-Dawley (SD), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY) rats that were untreated, treated with pertussis toxin, or treated with cholera toxin. The maximal responses, expressed as milligrams of tension, induced by clonidine (an α2-adrenoceptor agonist) and cirazoline (a selective α1-adrenoceptor agonist) were significantly greater in SHR than in SD or WKY, and the tissues were more sensitive to the agonists in SHR or SD than in WKY. Yohimbine (0.1 μM), a selective α2-adrenoceptor antagonist, shifted the dose-response curves for clonidine to the right. The effects of yohimbine were greater in SD than in WKY or SHR, but not different between WKY and SHR. Prazosin (0.05 μM), a selective α1-adrenoceptor antagonist, shifted the dose-response curves of cirazoline to the right, but the effects of prazosin were not different among these three strains of rats. Nifedipine (0.05 μM) completely blocked the response to clonidine in SD and WKY; however,in SHR, approximately one-third of the response to clonidine was resistant to nifedipine. Nifedipine, at 0.05 μM, only partially inhibited responses to cirazoline in SD, SHR, and WKY, and no differences were noted between the strains. Pertussis toxin pretreatment (50 μg/kg, 3 days before experiment) almost completely blocked the responses to clonidine, but only partially inhibited those to cirazoline. After pertussis toxin pretreatment, the responses (maximal effects and EC50s) to clonidine and cirazoline were not significantly different in arteries from the three strains of rats. A combination of pertussis toxin and nifedipine resulted in an additive inhibition of the responses induced by cirazoline. cholera toxin pretreatment (0.3 mg/kg, 3 days before experiment), however, had no effects on the contractile responses induced by either clonidine or cirazoline, or on the inhibitory effects of nifedipine in SHR, SD, and WKY. These results indicate that (i) the maximal responses to α1- and α2-adrenoceptor agonists are enhanced in rat tail artery rings from SHR; (ii) tissues from SH and SD rats are also more sensitive to cirazoline and clonidine than are tissues from WKY: (iii) responses to clonidine, but not cirazoline, in tissues from the SHR are less sensitive to nifedipine than tissues from SD and WKY; (iv) a G-protein sensitive to pertussis but not cholera toxin is involved in the regulation of both α1- and α2-adrenoceptor signal transduction processes in rat tail artery smooth muscle; and (v) pretreatment with pertussis toxin reduces the enhanced response levels of SHR tissues so that the maximal contractile responses to both α1- and α2-adrenoceptor agonists are equivalent in arteries from the three strains of rats.

AB - The α1- and α2-adrenoceptor-stimulated contractile responses of rat tail artery rings were compared in Sprague-Dawley (SD), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY) rats that were untreated, treated with pertussis toxin, or treated with cholera toxin. The maximal responses, expressed as milligrams of tension, induced by clonidine (an α2-adrenoceptor agonist) and cirazoline (a selective α1-adrenoceptor agonist) were significantly greater in SHR than in SD or WKY, and the tissues were more sensitive to the agonists in SHR or SD than in WKY. Yohimbine (0.1 μM), a selective α2-adrenoceptor antagonist, shifted the dose-response curves for clonidine to the right. The effects of yohimbine were greater in SD than in WKY or SHR, but not different between WKY and SHR. Prazosin (0.05 μM), a selective α1-adrenoceptor antagonist, shifted the dose-response curves of cirazoline to the right, but the effects of prazosin were not different among these three strains of rats. Nifedipine (0.05 μM) completely blocked the response to clonidine in SD and WKY; however,in SHR, approximately one-third of the response to clonidine was resistant to nifedipine. Nifedipine, at 0.05 μM, only partially inhibited responses to cirazoline in SD, SHR, and WKY, and no differences were noted between the strains. Pertussis toxin pretreatment (50 μg/kg, 3 days before experiment) almost completely blocked the responses to clonidine, but only partially inhibited those to cirazoline. After pertussis toxin pretreatment, the responses (maximal effects and EC50s) to clonidine and cirazoline were not significantly different in arteries from the three strains of rats. A combination of pertussis toxin and nifedipine resulted in an additive inhibition of the responses induced by cirazoline. cholera toxin pretreatment (0.3 mg/kg, 3 days before experiment), however, had no effects on the contractile responses induced by either clonidine or cirazoline, or on the inhibitory effects of nifedipine in SHR, SD, and WKY. These results indicate that (i) the maximal responses to α1- and α2-adrenoceptor agonists are enhanced in rat tail artery rings from SHR; (ii) tissues from SH and SD rats are also more sensitive to cirazoline and clonidine than are tissues from WKY: (iii) responses to clonidine, but not cirazoline, in tissues from the SHR are less sensitive to nifedipine than tissues from SD and WKY; (iv) a G-protein sensitive to pertussis but not cholera toxin is involved in the regulation of both α1- and α2-adrenoceptor signal transduction processes in rat tail artery smooth muscle; and (v) pretreatment with pertussis toxin reduces the enhanced response levels of SHR tissues so that the maximal contractile responses to both α1- and α2-adrenoceptor agonists are equivalent in arteries from the three strains of rats.

KW - α-adrenoceptor

KW - α-adrenoceptor

KW - cholera toxin

KW - pertussis toxin

KW - rat tail artery ring

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