Cardiovascular effects of angiotensin-(1-7) injected into the dorsal medulla of rats.
The amino terminal angiotensin heptapeptide, Asp-Arg-Val-Tyr-Ile-His-Pro [ANG-(1-7)], is the major product formed during incubation of 125I-labeled ANG I or 125I-labeled ANG II with homogenates obtained from canine dorsomedial medulla oblongata. To determine whether ANG-(1-7) has central-mediated cardiovascular effects, this heptapeptide was microinjected into the dorsal medulla of chloralose-urethan-anesthetized rats. Unilateral injections of ANG-(1-7) into the medial nucleus tractus solitarii caused depressor and bradycardic effects at doses between 0.1 and 12.5 ng. Similar hypotensive responses accompanied with bradycardia were produced by injections of ANG-(1-7) into the dorsal motor nucleus of the vagus. In both nuclei, the monophasic depressor responses elicited by ANG-(1-7) were qualitatively similar to those found with injections of ANG II. Biphasic depressor-pressor responses of variable magnitude were produced by the injection of either angiotensin peptide at a high dose (250 ng). Because ANG-(1-7) has no direct vascular or dipsogenic effects, our findings suggest important differences in the receptor requirements for vascular and neural tissue of the dorsal medulla. Moreover, the data support the concept of tissue specific formation and action of angiotensin peptides in the brain.
Campagnole-Santos
M J
MJ
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio 44195.
Diz
D I
DI
Santos
R A
RA
Khosla
M C
MC
Brosnihan
K B
KB
Ferrario
C M
CM
D000803:Angiotensin I; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)