title: Effects of angiotensin II type 1 receptor antagonist on pressor responses to pulsatile compression of the rostral ventrolateral medulla in rats.
abstract: The rostral ventrolateral medulla (RVLM) is known to be a major center regulating sympathetic and cardiovascular activities. A possible association between neurovascular compression of the RVLM and essential hypertension has been indicated. The present study was performed to determine the role of angiotensin II (AngII) in the pressor and sympathetic responses to pulsatile compression of the RVLM. To determine the role of glutamate and AngII in the RVLM, L-glutamate (Glu) 2 nmol or AngII 100 pmol was injected into the RVLM with or without RVLM pretreatment of kynurenate (Glu receptor antagonist) 3nmol, candesartan (AngII type 1 (AT1) receptor antagonist) 2 nmol, or PD123319 (AngII type 2 (AT2) receptor antagonist) 1 nmol in anesthetized Wistar rats. In addition, to determine the role of glutamate and AngII in the pressor and sympathetic effects to the RVLM compression, kynurenate, candesartan, or PD123319 was locally injected before pulsatile compression of the RVLM. Finally, to determine the effects of peripherally administered AngII antagonists in these pressor and sympathetic excitatory responses, candesartan 0.25 micromol or PD123319 0.05 micromol was intravenously injected before pulsatile compression of the RVLM. Glu injected into the RVLM significantly increased mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (SNA), and these effects were reduced by RVLM pretreatment with kynurenate, but were unaffected by candesartan or PD123319. AngII injected into the RVLM and pulsatile compression of the RVLM also increased MAP and SNA. However, in contrast with Glu injections, these effects were reduced by RVLM pretreatment with candesartan or kynurenate, but were unaffected by PD123319. Pressor and sympathetic excitatory responses to RVLM compression were reduced by intravenous pretreatment with candesartan but not with PD123319. These results indicate that, upon pulsatile compression of the RVLM, AngII may activate RVLM neurons via AT1 receptors and stimulate Glu release to thereby elicit sympathetic activation and pressor effects. Candesartan may exert its hypotensive effect at least in part by affecting the RVLM neurons to reduce sympathetic outflow induced by pulsatile compression of the RVLM.
authors.affiliation: Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kido
authors.forename: Susumu
authors.initials: S
authors.lastname: Sasaki
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Oguni
authors.forename: Sanae
authors.initials: S
authors.lastname: Harada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morimoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takeda
authors.forename: Masao
authors.initials: M
authors.lastname: Nakagawa
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D007275:Injections, Intravenous; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000098:blood supply* / Q000503:physiopathology*; D011673:Pulsatile Flow / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology; D013777:Tetrazoles / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D018691:Excitatory Amino Acid Antagonists; D007093:Imidazoles; D011725:Pyridines; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C073402:PD 123319; D018698:Glutamic Acid; D007736:Kynurenic Acid; C081643:candesartan