Differential modulation of norepinephrine-induced contractile response by ryanodine and verapamil in the isolated aortic ring of spontaneously hypertensive and Wistar-Kyoto rats.
Using ryanodine and verapamil, we compared the relative contributions of SR Ca2+ release and gated Ca2+ entry in arterial contractions induced by norepinephrine (NE) between spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Aortic rings of 10 SHR and 10 WKY aged 10-12 weeks were superfused in small water-jacketed tissue chambers with physiological salt solution and isometric tension was measured. The inhibition of the NE (3 x 10(-8) M)-induced contraction of aortic rings by ryanodine (10 microM) was significantly greater in WKY (40.1 +/- 6.9%) than in SHR (2.2 +/- 9.0%) (p less than 0.01). The inhibition of the NE-induced contraction by verapamil (10 microM) in the presence or absence of ryanodine (10 microM) was significantly greater in SHR than in WKY. The residual ryanodine and verapamil-insensitive component of NE-induced contraction was significantly greater in WKY than in SHR. Caffeine (5 mM)-induced contraction in the presence of verapamil and phentolamine was significantly smaller in SHR than in WKY. These results suggest that gated Ca2+ entry plays a more important role in Ca2+ control and that ryanodine-sensitive Ca2+ store is smaller, or the ryanodine receptor is altered in these tissues of SHR compared with those of WKY.
Department of Medicine, National Cardiovascular Center, Osaka, Japan.
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Ashida
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Yoshimi
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Kawano
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Yoshida
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Kuramochi
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Omae
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D009994:Osmolar Concentration; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012433:Ryanodine / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D012433:Ryanodine; D014700:Verapamil; D009638:Norepinephrine