Age-related involvement of the endothelium in beta-adrenoceptor-mediated relaxation of rat aorta.
The signalling pathway involved in beta-adrenoceptor relaxation was studied in aortas from rats either 8 or 54 weeks of age. The vasorelaxation produced by isoprenaline was almost completely abolished by endothelium removal in 54-week aortas, whereas in 8-week aortas, the effect was much smaller. The nitric oxide synthase inhibitor N-methyl-1-arginine acetate (L-NMMA) partially attenuated the isoprenaline induced relaxation to a similar extent in both age groups when the endothelium was intact, suggesting that although nitric oxide was involved, it could not explain the age-related difference. The K(+) channel inhibitor, tetraethylammonium inhibited isoprenaline vasorelaxation to a larger degree in 54-week compared to 8-week aortas indicating that K(+) channels were responsible for the age-related differences. We suggest that as the animals age, the smooth muscle cyclic AMP signalling system declines, and that this is compensated for by an alternate pathway involving the opening of K(+) channels.
van der Zypp
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Department of Medical Laboratory Science, RMIT University, PO Box 2476V, 3001, Melbourne, Australia. andrea.vanderzypp@rmit.edu.au
Kang
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Majewski
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D001030:Apamin / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010455:Peptides / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D010455:Peptides; D015221:Potassium Channels; D011943:Receptors, Adrenergic, beta; D018999:Charybdotoxin; D010656:Phenylephrine; D001030:Apamin; D019323:omega-N-Methylarginine; D001262:Atenolol; C064719:iberiotoxin; D019001:Nitric Oxide Synthase; D007545:Isoproterenol