Bohmann C, Rist W, Schollmeyer P, Rump L C
Medizinische Universitätsklinik Freiburg, Innere Medizin IV, Freiburg, Germany.
Cardiovasc Res. 1995 Dec;30(6):857-65.
The aim of the present study was to evaluate the role of vascular alpha 1- and alpha 2-adrenoceptors in kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY).
SHR and WKY kidneys (12-14 weeks) were isolated and perfused with Krebs-Henseleit solution. Concentration-response curves for the alpha 1-adrenoceptor agonist methoxamine and the alpha 2-adrenoceptor agonist UK 14304 were constructed alone and in the presence of the alpha 1-adrenoceptor antagonist prazosin, the alpha 2-adrenoceptor antagonist idazoxan and exogenous angiotensin II.
Methoxamine induced a maximal pressor response of 247 +/- 9 mmHg with an EC50 of 1.3 +/- 0.1 microM in SHR and of 193 +/- 4 mmHg with an EC50 of 1.1 +/- 0.1 microM in WKY. The concentration-response curve for methoxamine was shifted to the right by prazosin with a pA2 value of 9.29 (SHR) and 9.26 (WKY) and by idazoxan with a pA2 value of 6.45 (SHR) and 6.33 (WKY). UK 14304 induced a maximal pressor response of 41 +/- 12 mmHg in SHR and of 37 +/- 8 mmHg in WKY. Angiotensin II (0.1 nM) did not significantly alter pressor responses to methoxamine but caused a marked shift to the left of the concentration-response curve for UK 14304. UK 14304 then induced a maximal pressor response of 92 +/- 13 mmHg with an EC50 of 0.07 +/- 0.01 microM in SHR and of 78 +/- 14 mmHg with an EC50 of 0.14 +/- 0.01 microM in WKY. In the presence of angiotensin II (0.1 nM) the concentration-response curve for UK 14304 was shifted to the right by prazosin with a pKB of 6.36 (SHR) and 6.33 (WKY) and by idazoxan with a pKB of 7.68 (SHR) and 7.65 (WKY).
The results demonstrate a predominant role of vasoconstrictory alpha 1-adrenoceptors over alpha 2-adrenoceptors in SHR and WKY isolated kidneys. Low physiological concentrations of angiotensin II unmask functional vascular alpha 2-adrenoceptors which are slightly more sensitive in SHR than in WKY kidneys.
本研究旨在评估血管α1 - 和α2 - 肾上腺素能受体在自发性高血压大鼠（SHR）和正常血压的Wistar Kyoto大鼠（WKY）肾脏中的作用。
分离SHR和WKY大鼠（12 - 14周龄）的肾脏，并用Krebs - Henseleit溶液进行灌注。单独以及在存在α1 - 肾上腺素能受体拮抗剂哌唑嗪、α2 - 肾上腺素能受体拮抗剂咪唑克生和外源性血管紧张素II的情况下，构建α1 - 肾上腺素能受体激动剂甲氧明和α2 - 肾上腺素能受体激动剂UK 14304的浓度 - 反应曲线。
甲氧明在SHR中诱导的最大升压反应为247±9 mmHg，EC50为1.3±0.1 μM；在WKY中诱导的最大升压反应为193±4 mmHg，EC50为1.1±0.1 μM。哌唑嗪使甲氧明的浓度 - 反应曲线右移，SHR的pA2值为9.29，WKY的pA2值为9.26；咪唑克生也使曲线右移，SHR的pA2值为6.45，WKY的pA2值为6.33。UK 14304在SHR中诱导的最大升压反应为41±12 mmHg，在WKY中为37±8 mmHg。血管紧张素II（0.1 nM）未显著改变对甲氧明的升压反应，但使UK 14304的浓度 - 反应曲线明显左移。之后，UK 14304在SHR中诱导的最大升压反应为92±13 mmHg，EC50为0.07±0.01 μM；在WKY中诱导的最大升压反应为78±14 mmHg，EC50为0.14±0.01 μM。在存在血管紧张素II（0.1 nM）的情况下，哌唑嗪使UK 14304的浓度 - 反应曲线右移，SHR的pKB为6.36，WKY的pKB为6.33；咪唑克生也使曲线右移，SHR的pKB为7.68，WKY的pKB为7.65。
结果表明，在SHR和WKY分离的肾脏中，血管收缩性α1 - 肾上腺素能受体比α2 - 肾上腺素能受体起主要作用。低生理浓度的血管紧张素II可揭示功能性血管α2 - 肾上腺素能受体，其在SHR肾脏中比在WKY肾脏中稍敏感。
