Endothelin-A receptors and NO mediate decrease in arterial pressure during recovery from restraint.
We investigated the role of central endothelin-A (ET(A)) receptors and nitric oxide (NO) in regulating arterial pressure during restraint stress and recovery from stress. Rats received intracerebroventricular (icv) injections of the ET(A) receptor antagonist BQ123 (24 microg/kg) and were then subjected to two restraint-rest cycles (1 h of restraint and 1 h of rest/cycle). Although mean arterial pressure (MAP) values in BQ123-treated and control rats increased at the onset of restraint and remained elevated during restraint, MAP values in BQ123-treated rats were consistently greater than in control rats. During rest periods, MAP values in control rats decreased to below baseline levels, whereas those in BQ123-treated rats remained significantly higher. NO content was decreased in the brain stems of BQ123-treated compared with control rats after the 4-h protocol. Injections (icv) of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine (L-NNA) eliminated the decreases in MAP values during rest periods in both BQ123-treated and control rats. Inhibition of neuronal NOS with icv injection of 7-nitroindazole sodium salt resulted in MAP values intermediate between control rats and rats receiving L-NNA. These results support the hypothesis that endothelin acts through ET(A) receptors in the brain, possibly via release of NO, to decrease arterial pressure during restraint and recovery from restraint.
Yip
Avery W C
AW
Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Krukoff
Teresa L
TL
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology*; D020127:Recovery of Function / Q000502:physiology; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000209:etiology / Q000503:physiopathology
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D007191:Indazoles; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat; C072247:cyclo(Trp-Asp-Pro-Val-Leu); C080122:7-nitroindazole