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(Hypertension. 1999;34:222-228.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Impaired Isoproterenol-Induced Hyperpolarization in Isolated Mesenteric Arteries of Aged Rats

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

From the Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

Correspondence to Koji Fujii, MD, PhD, Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. E-mail fujii{at}intmed2.med.kyushu-u.ac.jp

Abstract—Stimulation of vascular ß-adrenoceptors leads to membrane hyperpolarization, presumably via the ß-adrenoceptor/G_s protein/adenylate cyclase signaling cascade; the ionic mechanisms of this phenomenon remain unclear. ß-Adrenoceptor–mediated vascular relaxation is impaired with aging; however, little is known concerning whether ß-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. Isoproterenol-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) (3x10^-6 mol/L; -3.1 versus -9.9 mV; P<0.001; n=8 to 9). Cholera toxin (10^-9 g/mL), an 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 ß-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.

Key Words: receptors, adrenergic, beta • hyperpolarization • potassium channels • aging • muscle, smooth, vascular

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