Kurahashi K, Akimoto Y, Usui H, Jino H
Pharmacology Division, Kyoto University, Japan.
Life Sci. 1992;51(9):695-702. doi: 10.1016/0024-3205(92)90243-i.
Nifedipine-resistant Ca(++)-induced contractions (NR-Ca(++)-contraction) were compared in the tail arteries from SHRs and WKYs (5 and 13 week old). NR-Ca(++)-contraction of tail artery was defined as follows: Ca(++)-induced contraction in the presence of norepinephrine (NE) (10(-5) M) or 5-hydroxytryptamine (5-HT) (10(-5) M) in Ca(++)-free medium containing EGTA (0.1 mM) and nifedipine (10(-6) M). NR-Ca(++)-contractions in arteries from 5 week old SHRs and WKYs were not different. In contrast, NR-Ca(++)-contractions in arteries from 13 week old SHRs were about 2-fold greater than in arteries from 13 week old WKYs. In arteries from 13 week old WKYs and SHRs, nitroglycerin (10(-5) M) significantly reduced the NR-Ca(++)-contraction in the presence of 5-HT but not in the presence of NE. The reduction was inhibited by the presence of methylene blue (3 x 10(-6) M). 8-Bromo-cGMP (10(-4) M) reduced significantly the NR-Ca(++)-contraction in the presence of 5-HT in arteries from 13 week old SHRs and WKYs. The present experiments clearly demonstrated that the NR-Ca(++)-contractions (both in the presence of NE and 5-HT) in 13 week old SHRs were significantly greater than those in arteries from 13 week old WKYs. These results suggest that in addition to an increase in voltage-operated Ca++ mobilization reported by others, an increase in NR-Ca++ mobilization may contribute to the development of hypertension in SHR.
比较了自发性高血压大鼠(SHRs)和Wistar-Kyoto大鼠(WKYs)(5周龄和13周龄)尾动脉中硝苯地平抵抗性Ca(++)诱导的收缩(NR-Ca(++)收缩)。尾动脉的NR-Ca(++)收缩定义如下:在含有乙二醇双四乙酸(EGTA)(0.1 mM)和硝苯地平(10(-6) M)的无Ca(++)培养基中,去甲肾上腺素(NE)(10(-5) M)或5-羟色胺(5-HT)(10(-5) M)存在时Ca(++)诱导的收缩。5周龄SHRs和WKYs动脉中的NR-Ca(++)收缩无差异。相反,13周龄SHRs动脉中的NR-Ca(++)收缩比13周龄WKYs动脉中的约大2倍。在13周龄WKYs和SHRs的动脉中,硝酸甘油(10(-5) M)在5-HT存在时显著降低NR-Ca(++)收缩,但在NE存在时则不然。亚甲蓝(3×10(-6) M)存在时可抑制这种降低。8-溴环鸟苷酸(10(-4) M)在13周龄SHRs和WKYs动脉中5-HT存在时显著降低NR-Ca(++)收缩。本实验清楚地表明,13周龄SHRs中的NR-Ca(++)收缩(在NE和5-HT存在时)显著大于13周龄WKYs动脉中的收缩。这些结果表明,除了其他人报道的电压依赖性Ca++动员增加外,NR-Ca++动员增加可能也有助于SHR高血压的发展。