The cardiovascular effects of angiotensin-(1-7) in the rostral and caudal ventrolateral medulla of the rabbit

Previous studies in the rat have indicated that the heptapeptide angiotensi n-(1-7) has an excitatory action on presser neurons in the rostral ventrola teral medulla that is equipotent to that evoked by angiotensin II, but whic h is mediated by separate receptors. In this study we have compared the car diovascular effects and mechanisms of action of angiotensin-(1-7) with angi otensin II in the rostral and caudal ventrolateral medulla of the rabbit, a species which, unlike the rat, contains a high density of angiotensin rece ptors, similar to that observed in humans. Microinjections of angiotensin-( 1-7) into the rostral and caudal ventrolateral medulla evoked dose-dependen t increases and decreases, respectively, in arterial pressure and renal sym pathetic nerve activity, but in comparison to angiotensin II much higher do ses (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, receptor antagonist lo sartan. The results demonstrate that in the rabbit angiotensin-(1-7) can ex cite presser and depressor neurons in the ventrolateral medulla, but indica te that these effects are mediated by AT(1) receptors. The much lower poten cy 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, i n contrast to the rat, the results do not indicate that angiotensin-(1-7) h as a biologically significant action in the ventrolateral medulla of the ra bbit. (C) 2000 Elsevier Science B.V. All rights reserved.