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Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15620
Injection of sarthran,
an angiotensin receptor antagonist, bilaterally into the rostral
ventrolateral medulla (RVLM) of
-chloralose-anesthetized rats
decreases arterial pressure (AP) to the same extent as total autonomic
blockade. This response is not reproduced by selective AT1
antagonists. To examine the pharmacological profile of the response
elicited by [Sar1, Thr8]ANG II (sarthran),
the ability of angiotensin analogs to inhibit the effect of sarthran
injected into the RVLM was tested. Coinjection of angiotensin II (ANG
II) prevented the sarthran-evoked decrease in AP, but this action of
ANG II was markedly attenuated by pretreatment of the RVLM with the
aminopeptidase inhibitor amastatin. Coinjection of
ANG(3-8) or a selective agonist of AT4
receptors prevented the effect of sarthran injected into the RVLM.
ANG(1-7) was also able to prevent the effect of
sarthran. None of the angiotensin fragments tested substantially
altered blood pressure when injected alone into the RVLM. These results
suggest that the depressor action of sarthran injected into the RVLM is
not dependent on ANG II receptors, though the nature of the site or
sites of action of sarthran within the RVLM remains uncertain.
angiotensin; angiotensin antagonist; angiotensin AT4 receptor; neural control of blood pressure
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