Impaired isoproterenol-induced hyperpolarization in isolated mesenteric arteries of aged rats

Koji Fujii, Uran Onaka, Kenichi Goto, Abe Isao, Masatoshi Fujishima

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31 Citations (Scopus)


Stimulation of vascular β-adrenoceptors leads to membrane hyperpolarization, presumably via the β-adrenoceptor/G(s) protein/adenylate cyclase signaling cascade; the ionic mechanisms of this phenomenon remain unclear. β-Adrenoceptor-mediated vascular relaxation is impaired with aging; however, little is known concerning whether β-adrenoceptor-mediated hyperpolarization is altered with aging. We sought to determine the ionic mechanisms of isoproterenol-induced hyperpolarization in the rat mesenteric resistance artery, as well as the age-related changes in isoproterenol- induced hyperpolarization and their underlying mechanisms. Isoprotereno- induced hyperpolarization was inhibited by high-K+ solution and glibenclamide (10-6 mol/L), an inhibitor of ATP-sensitive K+ channels (K(ATP)), but not by apamin, iberiotoxin, or charybdotoxin, inhibitors of Ca2+-activated K+ channels. Isoproterenol-induced hyperpolarization was markedly less in aged rats (≥24 months) than in adults rats (12 to 20 weeks) (3 x 10-6 tool/L; -3.1 versus -9.9 mV; P<0.001; n=8 to 9). Cholera toxin (10-9 g/mL), all activator of G(s), evoked hyperpolarization only in adult rats. Hyperpolarization to forskolin, a direct activator of adenylate cyclase, was also reduced to some extent in aged rats (10-5 mol/L; -8.8 versus -13 mV; P<0.05; n=6), whereas hyperpolarization to levcromakalim, a K(ATP) opener, was comparable in both groups. These findings suggest that isoproterenol elicits hyperpolarization via an opening of K(ATP) in the rat resistance artery and that isoproterenol-induced hyperpolarization is attenuated in aged rats mainly because of a defective coupling of β- adrenoceptors to adenylate cyclase and partly because of a defect at the level of adenylate cyclase, but not because of an alteration of K(ATP) per se.

Original languageEnglish
Pages (from-to)222-228
Number of pages7
Issue number2
Publication statusPublished - Aug 1999

All Science Journal Classification (ASJC) codes

  • Internal Medicine


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