Pharmacological profile of depressor response elicited by sarthran in rat ventrolateral medulla.
Injection of sarthran, an angiotensin receptor antagonist, bilaterally into the rostral ventrolateral medulla (RVLM) of alpha-chloralose-anesthetized rats decreases arterial pressure (AP) to the same extent as total autonomic blockade. This response is not reproduced by selective AT(1) antagonists. To examine the pharmacological profile of the response elicited by [Sar(1), Thr(8)]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 AT(4) 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.
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Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15620, USA.
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D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D010455:Peptides; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
C090830:AT4 receptor; D057911:Angiotensin Receptor Antagonists; D000900:Anti-Bacterial Agents; D000959:Antihypertensive Agents; D018756:GABA Antagonists; D010455:Peptides; D011480:Protease Inhibitors; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D009118:Muscimol; C014805:angiotensin II, Sar(1)-Thr(8)-; C016977:amastatin; D019808:Losartan