Colas B, Slama M, Masson H, Colas J L, Collin T, Arnould M L, Hary L, Safar M, Andrejak M
Laboratoire de pharmacologie et physiopathologie cardiovasculaire, faculté de médecine, Amiens, France.
Fundam Clin Pharmacol. 2000 Jul-Aug;14(4):363-8. doi: 10.1111/j.1472-8206.2000.tb00417.x.
In vitro experiments were designed to assess the inhibitory effect of the thiazide diuretics methyclothiazide (MCTZ), the hydrochlorothiazide (HCTZ), and the thiazide-related diuretic indapamide (IND) on contractile responses to norepinephrine (NE) and arginine vasopressin (AVP) of aortic rings from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Changes in the tension of aortic ring preparations were measured isometrically. MCTZ (10(-4) M) induced endothelium-dependent inhibition of the vasoconstrictor responses to NE and AVP only in aortas from SHR, and the maximal vasoconstrictive effect of NE and AVP was decreased by 59 +/- 11% and 32.3 +/- 13%, respectively. Indapamide (10(-4) M) also induced endothelium-dependent inhibition of the contractile response to AVP in aortic rings from SHR, and the maximal vasoconstrictive effect of AVP was decreased by 33 +/- 5%. In contrast, HCTZ did not inhibit the contractile response to either NE or AVP, even at the highest concentration. This study provides evidence that methyclothiazide and indapamide inhibit the contractile response induced by norepinephrine and/or arginine vasopressin on SHR aortic preparations via an endothelium-dependent mechanism.
体外实验旨在评估噻嗪类利尿剂甲氯噻嗪（MCTZ）、氢氯噻嗪（HCTZ）以及噻嗪类相关利尿剂吲达帕胺（IND）对自发性高血压大鼠（SHR）和正常血压的Wistar Kyoto大鼠（WKY）主动脉环对去甲肾上腺素（NE）和精氨酸加压素（AVP）收缩反应的抑制作用。通过等长方式测量主动脉环制剂的张力变化。MCTZ（10⁻⁴ M）仅在SHR的主动脉中诱导对NE和AVP血管收缩反应的内皮依赖性抑制，NE和AVP的最大血管收缩效应分别降低了59±11%和32.3±13%。吲达帕胺（10⁻⁴ M）也在SHR的主动脉环中诱导对AVP收缩反应的内皮依赖性抑制，AVP的最大血管收缩效应降低了33±5%。相比之下，即使在最高浓度下，HCTZ也不抑制对NE或AVP的收缩反应。本研究提供了证据，表明甲氯噻嗪和吲达帕胺通过内皮依赖性机制抑制去甲肾上腺素和/或精氨酸加压素对SHR主动脉制剂诱导的收缩反应。
