Blood pressure responses of endothelin-1 1-31 within the rostral ventrolateral medulla through conversion to endothelin-1 1-21.
Endothelin-1 1-31 (ET-1 1-31), a novel member of the endothelin family comprising 31 amino acids and derived from the selective hydrolysis of big ET-1 by chymase, directly activates endothelin receptors or converts to ET-1 1-21 by ET converting enzyme (ECE). The cardiovascular effects of central ET-1 1-31 are not identified. The present study was designed to investigate the cardiovascular actions of ET-1 1-31 within the rostral ventrolateral medulla (RVLM) in anesthetized rats. Bilateral injection of ET-1 1-31 (0.5, 1, and 2 pmol for each side) into the rostral ventrolateral medulla produced an initial pressor and/or a long-lasting hypotensive action but did not affect HR. Unilateral microinjection of 2 and 4 pmol of ET-1 1-31 into the rostral ventrolateral medulla only produced a significant (P < 0.05) transient increase in blood pressure by an average of 13 and 12 mm Hg, respectively, whereas unilateral microinjection of 8 pmol of ET-1 1-31 produced a sustained fall in blood pressure (from 92 +/- 6 to 69 +/- 8 mm Hg, P < 0.05). The transient pressor effect of unilaterally injecting ET-1 1-31 (4 pmol) into the rostral ventrolateral medulla was completely abolished by pretreatment with either ETA receptor antagonist BQ123 (83 +/- 2 versus 84 +/- 5 mm Hg, P > 0.05) or ET converting enzyme inhibitor phosphoramidon (99 +/- 5 versus 99 +/- 7 mm Hg, P > 0.05) but not ETB receptor antagonist IRL1038 (89 +/- 6 versus 96 +/- 7 mm Hg, P < 0.05). In addition, prior injection of phosphoramidon also completely abolished the long-lasting hypotension of intra-RVLM ET-1 1-31 (8 pmol) but did not modify the depressor action of intra-RVLM ET-1 1-21 (from 100 +/- 6 to 76 +/- 8 mm Hg, P < 0.05). In conclusion, the current results suggest that the cardiovascular effects of intra-RVLM ET-1 1-31 might be the result of conversion of ET-1 1-31 to ET-1 1-21 through activation of ETA receptors.
Lu
Yan
Y
Department of Physiology, Second Military Medical University, Shanghai, China.
Wang
Wei-Zhong
WZ
Liao
Zhuan
Z
Yan
Xiao-Hong
XH
Tang
Chao-Shu
CS
Yuan
Wen-Jun
WJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006020:Glycopeptides / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000502:physiology
D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D006020:Glycopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; C419584:endothelin-1 (1-21); C114932:endothelin-1 (1-31); C072247:cyclo(Trp-Asp-Pro-Val-Leu); C008890:phosphoramidon