Mechanisms of 17 beta-oestradiol induced vasodilatation in isolated pressurized rat small arteries

L Shaw, M J Taggart, C Austin

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

1. The influence of 17 beta-oestradiol on pressurized isolated rat mesenteric and coronary small arteries was investigated. 2. 17 beta-oestradiol caused rapid (t1.0 < 5 mins) concentration-dependent relaxations of pre-contracted pressurized (50 mmHg) isolated rat mesenteric and coronary arteries. Similar responses were observed in both vessel types. Significant relaxations were only observed at concentrations exceeding 3 microM. 3. The vasodilatory responses in both types of artery were unaffected by 10 microM L-nitro arginine (L-NNA) alone or in the presence of 10 microM indomethacin, inhibitors of nitric oxide and prostaglandin synthesis respectively. They were also unaffected by the pre-contracting agent used i.e. high K+ or U46619 (a thromboxane analogue). 4. Neither the oestrogen receptor antagonist ICI 182,780 (10 microM) nor the protein synthesis inhibitor cycloheximide (100 microM) had any effect on the responses of mesenteric arteries to 17 beta-oestradiol. 5. 17 alpha-oestradiol had only a minor effect on mesenteric arterial diameter over a concentration range similar to the effective vasodilatory range for 17 beta-oestradiol. 6. Membrane impermeant 17 beta-oestradiol conjugated to bovine serum albumin (beta-oestradiol-17-hemisuccinate-BSA) (E-H-BSA) resulted in a vasodilatation of pressurized arteries. 7. Wortmannin, an inhibitor of myosin light chain kinase, near maximally relaxed pressurized mesenteric arteries although the time course for the response was significantly slower than that for 17 beta-oestradiol. 8. These results taken together suggest that the acute effects of 17 beta-oestradiol on isolated pressurized arterial tone may be due to effects directly on the vascular smooth muscle via non-genomic mechanisms that involve a stereospecific interaction at the plasma membrane.

Original languageEnglish
Pages (from-to)555-65
Number of pages11
JournalBritish Journal of Pharmacology
Volume129
Issue number3
DOIs
Publication statusPublished - 29 Feb 2000

Keywords

  • Androstadienes/pharmacology
  • Animals
  • Coronary Vessels/drug effects
  • Cycloheximide/pharmacology
  • Endothelium, Vascular/drug effects
  • Enzyme Inhibitors/pharmacology
  • Estradiol/analogs & derivatives
  • Fulvestrant
  • In Vitro Techniques
  • Male
  • Mesenteric Arteries/drug effects
  • Nitric Oxide Synthase/antagonists & inhibitors
  • Nitric Oxide Synthase Type III
  • Pressure
  • Protein Synthesis Inhibitors/pharmacology
  • Rats
  • Rats, Inbred WKY
  • Receptors, Estrogen/agonists
  • Vasodilation/drug effects
  • Wortmannin
  • omega-N-Methylarginine/pharmacology

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