Possible mechanism of the vasodepressor effect of endokinin a/b in anesthetized rats.
We investigated the mechanism of the vasodepressor effect of endokinin A/B. An intravenous (IV) bolus of endokinin A/B (0.05-0.3 nmol/kg) dose-dependently decreased mean arterial pressure in thiobutabarbital-anesthetized rats. The magnitude of the response was unaffected by IV pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, inhibitor of nitric oxide synthase), methylene blue (inhibitor of soluble guanylyl cyclase), indomethacin (cyclooxygenase inhibitor), or tetraethylammonium (TEA, nonspecific K+ channel blocker). L-NAME reduced the half-recovery time of the vasodepressor effect of endokinin A/B relative to responses in rats pretreated with either saline or norepinephrine, which caused a similar pressor effect as did L-NAME. Methylene blue, but not TEA or indomethacin, reduced the recovery time of the vasodepressor effect of endokinin A/B. Therefore, the vasodepressor effect of endokinin A/B is mediated via the nitric oxide/L-arginine pathway and activation of soluble guanylyl cyclase but not by production of prostanoids or opening of TEA-sensitive K+ channels.
Abdelrahman
Aly Mohamed
AM
Department of Pharmacology, College of Medicine and Health Sciences, Sultan Qaboos University, Sultanate of Oman.
Syyong
Harley
H
Tjahjadi
Anindita
A
Pang
Catherine Cheuk Ying
CC
D000758:Anesthesia; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001120:Arginine / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects*; D003864:Depression, Chemical; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists; D011453:Prostaglandins / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D015320:Tachykinins / Q000494:pharmacology*; D019789:Tetraethylammonium / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011453:Prostaglandins; D011498:Protein Precursors; C486037:TAC4 protein, human; D015320:Tachykinins; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D019789:Tetraethylammonium; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D006162:Guanylate Cyclase; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D007213:Indomethacin