Potts P D, Horiuchi J, Coleman M J, Dampney R A
Department of Physiology and Institute for Biomedical Research, F13, University of Sydney, NSW 2006, Sydney, Australia.
Brain Res. 2000 Sep 15;877(1):58-64. doi: 10.1016/s0006-8993(00)02626-3.
Previous studies in the rat have indicated that the heptapeptide angiotensin-(1-7) has an excitatory action on pressor neurons in the rostral ventrolateral medulla that is equipotent to that evoked by angiotensin II, but which is mediated by separate receptors. In this study we have compared the cardiovascular effects and mechanisms of action of angiotensin-(1-7) with angiotensin II in the rostral and caudal ventrolateral medulla of the rabbit, a species which, unlike the rat, contains a high density of angiotensin receptors, similar to that observed in humans. Microinjections of angiotensin-(1-7) into the rostral and caudal ventrolateral medulla evoked dose-dependent increases and decreases, respectively, in arterial pressure and renal sympathetic nerve activity, but in comparison to angiotensin II much higher doses (approximately 50-fold higher) were required to produce cardiovascular response of similar magnitude. The cardiovascular effects of angiotensin-(1-7) were blocked by prior injection of the selective antagonist [D-Ala(7)]-Ang-(1-7) but were also blocked by the selective AT(1) receptor antagonist losartan. The results demonstrate that in the rabbit angiotensin-(1-7) can excite pressor and depressor neurons in the ventrolateral medulla, but indicate that these effects are mediated by AT(1) receptors. The much lower potency of angiotensin-(1-7) as compared to angiotensin II may be explained as a consequence of it having a much lower affinity to AT(1) receptors. Thus, in contrast to the rat, the results do not indicate that angiotensin-(1-7) has a biologically significant action in the ventrolateral medulla of the rabbit.
以往对大鼠的研究表明，七肽血管紧张素 -（1 - 7）对延髓头端腹外侧的升压神经元具有兴奋作用，其作用强度与血管紧张素II相当，但由不同的受体介导。在本研究中，我们比较了血管紧张素 -（1 - 7）和血管紧张素II在兔延髓头端和尾端腹外侧的心血管效应及作用机制。与大鼠不同，兔体内含有高密度的血管紧张素受体，类似于人类中观察到的情况。向兔延髓头端和尾端腹外侧微量注射血管紧张素 -（1 - 7）分别引起动脉血压和肾交感神经活动呈剂量依赖性升高和降低，但与血管紧张素II相比，需要高得多的剂量（约高50倍）才能产生相似程度的心血管反应。血管紧张素 -（1 - 7）的心血管效应可被预先注射选择性拮抗剂[D - Ala(7)] - Ang -（1 - 7）阻断，但也可被选择性AT(1)受体拮抗剂氯沙坦阻断。结果表明，在兔体内，血管紧张素 -（1 - 7）可兴奋延髓腹外侧的升压和降压神经元，但表明这些效应是由AT(1)受体介导的。与血管紧张素II相比，血管紧张素 -（1 - 7）效力低得多，这可能是由于它对AT(1)受体的亲和力低得多所致。因此，与大鼠不同，结果并不表明血管紧张素 -（1 - 7）在兔延髓腹外侧具有生物学显著作用。
