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 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.
Potts
P D
PD
Department of Physiology and Institute for Biomedical Research, F13, University of Sydney, NSW 2006, Sydney, Australia.
Horiuchi
J
J
Coleman
M J
MJ
Dampney
R A
RA
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology; D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000803:Angiotensin I; C118790:angiotensin I (1-7)