Differential Modulation of Norepinephrine-Induced Contractile Response by Ryanodine and Verapamil in the Isolated Aortic Ring of Spontaneously Hypertensive and Wistar-Kyoto Rats

Abstract

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(3×10^-8 M)-induced contraction of aortic rings by ryanodine (10 µM) was significantly greater in WKY (40.1 ± 6.9 %) than in SHR (2.2 ± 9.0 %) (p < 0. 01). The inhibition of the NE-induced contraction by verapamil (10 µM) in the presence or absence of ryanodine (10 µM) 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.

Key Words:

• Sarcoplasmic reticulum
• Ryanodine
• Verapamil
• Arterial smooth muscle
• SHR