title: Pressor response to pulsatile compression of the rostral ventrolateral medulla mediated by nitric oxide and c-fos expression.
abstract: It has been reported that neurovascular compression of the rostral ventrolateral medulla might be causally related to essential hypertension. Recently, we found that pulsatile compression of the rostral ventrolateral medulla increases sympathetic nerve activity and elevates arterial pressure via activation of glutamate receptors in rats. We also found that increases in sympathetic and cardiovascular activities by microinjection of L-glutamate into the rostral ventrolateral medulla are mediated by c-fos expression-related substance(s) following activation of the nitric oxide-cyclic GMP pathway. Herein, we investigated whether responses to pulsatile compression are mediated by local activation of the nitric oxide-cyclic GMP pathway and/or c-fos expression-related substance(s) in rats. Increases in arterial pressure (15+/-1 mmHg), heart rate (9+/-1 b.p.m.), and sympathetic nerve activity (% change: 8.5+/-1.1%) induced by pulsatile compression were partially but significantly inhibited after local microinjection of a nitric oxide synthase inhibitor, L-N(G)-nitroarginine methyl ester (8+/-2 mmHg, 1+/-1 b.p.m., 4.0+/-1.3%; P<0.05 vs compression without pretreatment) or 7-nitroindazole (7+/-2 mmHg, 2+/-1 b.p.m., 4.0+/-1. 5%; P<0.05), or a soluble guanylate cyclase inhibitor, methylene blue (9+/-1 mmHg, 4+/-1 b.p.m., 4.1+/-1.4%; P<0.05). In addition, increases in arterial pressure, heart rate, and sympathetic nerve activity by pulsatile compression were significantly reduced 6 h after microinjection of antisense oligodeoxynucleotide to c-fos mRNA (2+/-2 mmHg, 2+/-1 b.p.m., 1.0+/-1.0%; P<0.05 vs sense oligodeoxynucleotide). These results suggest that increases in sympathetic and cardiovascular activities induced by pulsatile compression of the rostral ventrolateral medulla are mediated, at least in part, by local activation of the nitric oxide-cyclic GMP pathway and c-fos expression-related substance(s) in rats.
authors.affiliation: Second Department of Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. morimot@koto.kpu-m.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Morimoto
authors.forename: S
authors.initials: S
authors.lastname: Sasaki
authors.forename: S
authors.initials: S
authors.lastname: Miki
authors.forename: T
authors.initials: T
authors.lastname: Kawa
authors.forename: H
authors.initials: H
authors.lastname: Itoh
authors.forename: T
authors.initials: T
authors.lastname: Nakata
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: M
authors.initials: M
authors.lastname: Nakagawa
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016762:Genes, fos / Q000235:genetics / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D009569:Nitric Oxide; D018698:Glutamic Acid; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester