Luoh H F, Chan S H
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
Brain Res. 1998 Jan 26;782(1-2):73-82. doi: 10.1016/s0006-8993(97)01198-0.
We evaluated the endogenous action of angiotensin II (AII) and its active metabolite, angiotensin III (AIII), at the nucleus tractus solitarii (NTS) in the modulation of baroreceptor reflex (BRR) response, and the subtype(s) of angiotensin receptors involved in this process. Adult, male Sprague-Dawley rats that were anesthetized and maintained with pentobarbital sodium were used. Bilateral microinjection of AII or AIII (10, 20 or 40 pmol) into the NTS significantly and dose-dependently suppressed the BRR response, which was evoked by transient hypertension induced by phenylephrine (5 micrograms/kg, i.v.). The suppressive effect of AII (40 pmol) was reversed by co-administration of the non-peptide AT1 receptor antagonist, losartan (1.6 nmol), but only partially by the non-peptide AT2 receptor antagonist, PD-123319. On the other hand, both angiotensin receptor antagonists appreciably reversed the depressive action of AIII (40 pmol). Blocking the endogenous activity of the angiotensins by microinjection into the bilateral NTS of losartan (1.6 nmol) or PD-123319 (1.6 nmol) elicited a significant enhancement of the BRR response. An interruption of the conversion of AII to AIII with the aminopeptidase A inhibitor, amastatin (3.3 nmol), attenuated, but did not eliminate, the AII-induced inhibition of the BRR response. We conclude that whereas the endogenous AIII may exert a tonic inhibitory modulation on the BRR response by acting on both the AT1 and AT2 receptor subtypes, the same action of the endogenous AII engaged only the AT1 receptor subtype at the NTS. Furthermore, at least part of the suppressive action of AII may result from its metabolic conversion to AIII.
我们评估了血管紧张素II（AII）及其活性代谢产物血管紧张素III（AIII）在孤束核（NTS）对压力感受器反射（BRR）反应的调节中的内源性作用，以及参与该过程的血管紧张素受体亚型。使用成年雄性Sprague-Dawley大鼠，用戊巴比妥钠麻醉并维持。向NTS双侧微量注射AII或AIII（10、20或40 pmol）可显著且剂量依赖性地抑制由苯肾上腺素（5微克/千克，静脉注射）诱导的短暂性高血压所诱发的BRR反应。非肽类AT1受体拮抗剂氯沙坦（1.6 nmol）共同给药可逆转AII（40 pmol）的抑制作用，但非肽类AT2受体拮抗剂PD-123319只能部分逆转。另一方面，两种血管紧张素受体拮抗剂均可明显逆转AIII（40 pmol）的抑制作用。向双侧NTS微量注射氯沙坦（1.6 nmol）或PD-123319（1.6 nmol）以阻断血管紧张素的内源性活性可显著增强BRR反应。用氨肽酶A抑制剂阿马astatin（3.3 nmol）阻断AII向AIII的转化可减弱但不能消除AII诱导的对BRR反应的抑制作用。我们得出结论，内源性AIII可能通过作用于AT1和AT2受体亚型对BRR反应发挥紧张性抑制调节作用，而内源性AII在NTS仅通过AT1受体亚型发挥相同作用。此外，AII的抑制作用至少部分可能源于其代谢转化为AIII。
