Holck M I
Pharmaceutical Research Department, F. Hoffmann-La Roche & Co. Ltd., Basle, Switzerland.
Eur J Pharmacol. 1988 Mar 22;148(1):9-15. doi: 10.1016/0014-2999(88)90448-7.
The relationship between alpha 1-adrenoceptor reserve and the sensitivity of vasoconstrictor responses to Ca2+ entry blockade was investigated in isolated aortas from age-matched (13-15 weeks) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Noradrenaline (NA) elicited contractile responses with a greater potency (log EC50) in aorta from WKY (-8.7) than in those from SHR (-8.05). The dihydropyridine Ca2+ entry blocker, Ro 18-3981 (10(-6) M), suppressed the maximal NA responses more in aorta of SHR (-54%) than WKY (-14%). The dissociation constant (KA) of NA was similar in aortas of both strains. However, the difference between KA and EC50 values was greater in aorta of WKY (7.2 X) than in those from SHR (1.4 X). Pretreatment of WKY aorta with the irreversible alpha-blocker phenoxybenzamine (10(-9) M) enhanced the inhibitory effect of Ro 18-3981 (10(-6) M) against NA-induced contractions (-14 to -47%). Thus, a smaller alpha 1-adrenoceptor reserve could explain the greater sensitivity of NA-induced contractions in SHR aorta to Ca2+ entry blockade.
在年龄匹配（13 - 15周）的自发性高血压大鼠（SHR）和正常血压的Wistar - Kyoto大鼠（WKY）的离体主动脉中，研究了α1 - 肾上腺素能受体储备与血管收缩反应对Ca2 +内流阻断敏感性之间的关系。去甲肾上腺素（NA）在WKY大鼠主动脉（-8.7）中引起的收缩反应效力（log EC50）比SHR大鼠主动脉（-8.05）更高。二氢吡啶类Ca2 +内流阻滞剂Ro 18 - 3981（10^(-6) M）在SHR主动脉（-54%）中比在WKY主动脉（-14%）中更能抑制NA的最大反应。NA在两种品系主动脉中的解离常数（KA）相似。然而，KA与EC50值之间的差异在WKY主动脉（7.2倍）中比在SHR主动脉（1.4倍）中更大。用不可逆的α - 阻滞剂酚苄明（10^(-9) M）预处理WKY主动脉可增强Ro 18 - 3981（10^(-6) M）对NA诱导收缩的抑制作用（从-14%至-47%）。因此，较小的α1 - 肾上腺素能受体储备可以解释SHR主动脉中NA诱导收缩对Ca2 +内流阻断的更高敏感性。
