Effect of acidosis on the mechanism (s) of insulin-induced vasorelaxation in normal Wistar-Kyoto (WKY) rat aorta
The effect of acidosis on insulin-induced relaxation was studied in thoracic aortic rings (from Wistar–Kyoto (WKY) rats) with (+ED) or without (−ED) endothelium. The rings were mounted in normal (pH 7.4) or acidotic (pH 7.2) Krebs solution for isometric tension recording. Phenylephrine (PE, 3.0 µM...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | en |
| Published: |
Elsevier
2009
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| Subjects: | |
| Online Access: | http://eprints.um.edu.my/2417/1/Effect_of_acidosis_on_the_mechanism_%28s%29_of_insulin-induced_vasorelaxation_in_normal_Wistar-Kyoto_%28WKY%29_rat_aorta.pdf http://eprints.um.edu.my/2417/ http://www.sciencedirect.com/science/journal/01670115 |
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| Summary: | The effect of acidosis on insulin-induced relaxation was studied in thoracic aortic rings (from Wistar–Kyoto
(WKY) rats) with (+ED) or without (−ED) endothelium. The rings were mounted in normal (pH 7.4) or acidotic
(pH 7.2) Krebs solution for isometric tension recording. Phenylephrine (PE, 3.0 µM)-contracted tissues were
exposed to insulin in the presence or absence of various inhibitors. Insulin exerted similar concentrationdependent relaxation of +ED tissues in normal and acidotic pH. Endothelium denudation, significantly (pb 0.05)
reduced insulin effect in normal, but not acidotic pH. Under normal pH, treatment with L-NAME or methylene
blue significantly (pb 0.05) reduced insulin responses in the +ED (but not the −ED) tissues. The insulin effect
was also significantly (pb 0.05) inhibited by tetraethylammonium (TEA; BKCa blocker), 4-Aminopyridine (4-AP;
KV channel blocker), combined treatments (L-NAME+4-AP+TEA, in +ED tissues) or (4-AP+TEA, in −ED
tissues). In either +ED or −ED tissues, indomethacin (cyclo-oxygenase inhibitor), glibenclamide (KATP channel
blocker), barium chloride (Kir
channel blocker) or Ouabain (a Na+
/K+
-ATPase inhibitor) had no effect. Except for
methylene blue (effect on +ED tissues), none of the drug treatments inhibited insulin vasodilator effect in
acidosis (+ED or −ED tissues). These data indicate that insulin exerts an endothelium-dependent and -
independent vasodilatation in rat aorta which in normal pH is mediated via BKCa and Kv channels, including the
EDNO-cGMP cascade. Acidosis abolishes the endothelium-dependent relaxation mechanism unraveling a novel
mechanism that is as efficacious and is cGMP-, but not EDNO-, BKCa- or Kv-mediated. |
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