Doggrell S A, Surman A J
Department of Pharmacology and Clinical Pharmacology, School of Medicine, University of Auckland, New Zealand.
J Hypertens. 1995 Sep;13(9):1023-9. doi: 10.1097/00004872-199509000-00013.
To test the hypothesis that vascular beta 2-adrenoceptor hyporesponsiveness in spontaneously hypertensive rats (SHR) is not induced by increased blood pressure or venous hypertrophy.
We compared the attenuating effects or isoprenaline, sodium nitroprusside and verapamilon the portal veins from Wistar-Kyoto (WKY) rats and SHR. studied the effects of slowly reversible beta-adrenoceptor antagonists, bromoacetylalprenololmenthane (BAAM) and ICI 147798, on the isoprenaline responses in order to determine the affinity and fractional beta 2-adrenoceptor occupancy-response relationships for isoprenaline.
The SHR portal veins did not develop hypertrophy. There was a small reduction in the sensitivity to isoprenaline and a marked reduction in the maximum attenuation of hypertension caused by isoprenaline. The sensitivity and efficacy of sodium nitroprusside and verapamil were not altered by hypertension. BAAM and ICI 147798 inhibited the isoprenaline responses and reduced the maximum attenuation to isoprenaline. In the WKY rat portal vein the dissociation constant (KA) values for isoprenaline were independent of BAAM concentration, and was 1.78 +/- 0.32 x 10(-7) mol/l. Similar isoprenaline KA values were obtained from the ICI 147798 data and in the SHR portal vein. In the WKY rat portal vein, from the BAAM data, it was calculated that isoprenaline produced 50, 95 and 100% maximum responses by occupying 6 +/- 1, 20 +/- 3 and 43 +/- 5% (n = 21) of the available beta 2-adrenoceptors, respectively. Similar occupancy-response relationships were obtained in the WKY rat portal vein from the ICI 147798 data. At each level of isoprenaline response the receptor reserve was significantly smaller in the SHR than it was in the WKY rat portal vein. Thus, from the BAAM data, isoprenaline produced 50, 95 and 100% maximum responses by occupying 14 +/- 3, 33 +/- 6 and 58 +/- 7% (n = 15) of the available SHR portal vein beta 2-adrenoceptors, respectively.
The SHR portal vein displays a selective beta 2-adrenoceptor hyporesponsiveness in the absence of a raised blood pressure or hypertrophy. This beta 2-adrenoceptor-associated hyporesponsiveness consisted of a marked loss of maximum attenuation in response to isoprenaline and of beta 2-adrenoceptor reserve for isoprenaline responses.
验证自发性高血压大鼠（SHR）血管β2 -肾上腺素能受体反应性降低并非由血压升高或静脉肥厚所致这一假说。
我们比较了异丙肾上腺素、硝普钠和维拉帕米对Wistar - Kyoto（WKY）大鼠和SHR门静脉的舒张作用。研究了缓慢可逆性β -肾上腺素能拮抗剂溴乙酰阿普洛尔薄荷烷（BAAM）和ICI 147798对异丙肾上腺素反应的影响，以确定异丙肾上腺素的亲和力以及β2 -肾上腺素能受体占有率与反应的关系。
SHR门静脉未出现肥厚。对异丙肾上腺素的敏感性略有降低，异丙肾上腺素引起的高血压最大降幅显著减小。硝普钠和维拉帕米的敏感性和效能不受高血压影响。BAAM和ICI 147798抑制异丙肾上腺素反应并降低对异丙肾上腺素的最大降幅。在WKY大鼠门静脉中，异丙肾上腺素的解离常数（KA）值与BAAM浓度无关，为1.78±0.32×10⁻⁷mol/L。从ICI 147798数据以及SHR门静脉中获得了相似的异丙肾上腺素KA值。在WKY大鼠门静脉中，根据BAAM数据计算得出，异丙肾上腺素分别占据可用β2 -肾上腺素能受体的6±1%、20±3%和43±5%（n = 21）时产生50%、95%和100%的最大反应。从ICI 147798数据在WKY大鼠门静脉中获得了相似的占有率 - 反应关系。在每个异丙肾上腺素反应水平，SHR中的受体储备均显著低于WKY大鼠门静脉。因此，根据BAAM数据，异丙肾上腺素分别占据可用SHR门静脉β2 -肾上腺素能受体的14±3%、33±6%和58±7%（n = 15）时产生50%、95%和100%的最大反应。
在血压未升高或未出现肥厚的情况下，SHR门静脉表现出选择性β2 -肾上腺素能受体反应性降低。这种与β2 -肾上腺素能受体相关的反应性降低包括对异丙肾上腺素反应的最大降幅显著丧失以及异丙肾上腺素反应的β2 -肾上腺素能受体储备丧失。
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