Chen Ying-Yu, Doggrell Sheila A
Cardiovascular Pharmacology Group, Faculty of Medicine and Health Science, The University of Auckland, New Zealand.
J Pharm Pharmacol. 2002 Apr;54(4):515-22. doi: 10.1211/0022357021778790.
The objective of this study was to determine the responsiveness, affinity constants and beta-adrenoceptor reserves for isoprenaline on the isolated aorta in the maturation of normotensive and hypertensive rats. The effects of a very slowly reversible antagonist, bromoacetylal-prenololmenthane (BAAM), on the relaxant responses of the aortae of 5- and 14-week-old Wistar Kyoto normotensive rats (WKY) and spontaneously hypertensive rats (SHRs) to isoprenaline were determined. Five-week-old SHRs are pre-hypertensive and the aortic rings are less responsive to isoprenalinethan age-matched WKY (pD2 values: WKY, 8.40; SHRs, 8.03). Similar relaxant responses to forskol in were obtained on the aortae of 5- and 14-week-old WKY and SHRs. The K(A) value for isoprenaline at the aortic beta2-adrenoceptors of the 5-week-old WKY was 2.1 x 10(-7) M, and similar values were obtained on the aortae of 5-week-old SHR and 14-week-old WKY and SHRs. In the maturation of the WKY aortae from 5 to 14 weeks, there was a reduction in the maximum response, a major loss of sensitivity and a loss of beta2-adrenoceptor reserve for isoprenaline. On 5-week-old SHR aorta, the sensitivity to isoprenaline was 2.5-fold lower, and the beta2-adrenoceptor reserve was less than on age-matched WKY. In the development of hypertension on the SHR aorta from 5 to 14 weeks, there was a reduction in the maximum response to isoprenaline. At 14 weeks, the sensitivity and the beta-adrenoceptor reserve to isoprenaline were similar, but the maximum responses were lower on the SHR than WKY. As there are differences in pre-hypertensive SHR and age-matched WKY aortic responses to isoprenaline, it is no longer valid to consider that the loss of responsiveness to isoprenaline in hypertension is solely owing to the hypertension. There are no changes in affinity, but major changes in the sensitivity, maximum responses and aortic beta2-adrenoceptor reserves to isoprenaline in the maturation of normotensive and pre-hypertensive aortae.
本研究的目的是确定在正常血压和高血压大鼠成熟过程中，异丙肾上腺素对离体主动脉的反应性、亲和常数和β-肾上腺素能受体储备。测定了一种非常缓慢可逆的拮抗剂溴乙酰阿普洛尔薄荷烷（BAAM）对5周龄和14周龄Wistar Kyoto正常血压大鼠（WKY）和自发性高血压大鼠（SHR）主动脉对异丙肾上腺素舒张反应的影响。5周龄的SHR处于高血压前期，其主动脉环对异丙肾上腺素的反应性低于年龄匹配的WKY（pD2值：WKY为8.40；SHR为8.03）。在5周龄和14周龄的WKY和SHR主动脉上，对福斯高林获得了相似的舒张反应。5周龄WKY主动脉β2-肾上腺素能受体上异丙肾上腺素的K(A)值为2.1×10(-7)M，在5周龄SHR、14周龄WKY和SHR的主动脉上获得了相似的值。在WKY主动脉从5周龄到14周龄的成熟过程中，最大反应降低，敏感性大幅丧失，对异丙肾上腺素的β2-肾上腺素能受体储备丧失。在5周龄SHR主动脉上，对异丙肾上腺素的敏感性低2.5倍，β2-肾上腺素能受体储备低于年龄匹配的WKY。在SHR主动脉从5周龄到14周龄高血压发展过程中，对异丙肾上腺素的最大反应降低。在14周龄时，对异丙肾上腺素的敏感性和β-肾上腺素能受体储备相似，但SHR的最大反应低于WKY。由于高血压前期SHR和年龄匹配的WKY主动脉对异丙肾上腺素的反应存在差异，因此认为高血压中对异丙肾上腺素反应性丧失仅归因于高血压不再成立。在正常血压和高血压前期主动脉成熟过程中，对异丙肾上腺素的亲和力没有变化，但敏感性、最大反应和主动脉β2-肾上腺素能受体储备有重大变化。
