title: The inhibitory effect of ouabain on the response of slowly adapting pulmonary stretch receptors to hyperinflation in the rabbit.
abstract: The combined effects of ouabain (Na(+)-K(+) ATPase inhibitor) and hyperinflation (inflation volume=three tidal volumes) on slowly adapting pulmonary stretch receptors (SARs) were studied before and after administration of nifedipine (an L-type Ca(2+) channel blocker) and KB-R7943 (a reverse-mode Na(+)-Ca(2+) exchanger blocker) in anesthetized, artificially ventilated rabbits after bilateral vagotomy. Before ouabain administration, hyperinflation stimulated SAR activity. After 20 min of ouabain administration (30 microg/kg) the SARs increased discharge rates in normal inflation. Under these conditions, hyperinflation initially stimulated SAR activity but subsequently inhibited the activity at peak inflation. Additional administration of 60 microg/kg ouabain (total dose=90 microg/kg) caused a further stimulation of SAR activity, but 20 min later both normal inflation and hyperinflation resulted in a greater inhibition of the receptor activity. The hyperinflation-induced SAR inhibition in the presence of ouabain (30 microg/kg) was not significantly altered by administration of either nifedipine (2 and 4 mg/kg) or KB-R7943 (1 and 3 mg/kg). In another series of experiments, we further examined the combined effects of ouabain and hyperinflation in veratridine (a Na(+) channel opener, 40 microg/kg)-treated animals. After recovery from the veratridine effect on SAR activity, which vigorously stimulated the receptor activity, ouabain treatment (30 microg/kg) that silenced the receptor activity at peak inflation greatly inhibited hyperinflation-induced SAR stimulation. These results suggest that hyperinflation-induced SAR inhibition in the presence of ouabain may be related to a Na(+) overload, but not to a Ca(2+) influx via activation of L-type Ca(2+) channels, in the SAR endings.
authors.affiliation: Department of Physiology, Nippon Dental University, School of Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan. matsu-s@tky.ndu.ac.jp
authors.forename: Shigeji
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Mizuho
authors.initials: M
authors.lastname: Ikeda
authors.forename: Shinki
authors.initials: S
authors.lastname: Yoshida
authors.forename: Toshimi
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Itoh
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Fujimi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanimoto
authors.forename: Chikako
authors.initials: C
authors.lastname: Saiki
authors.forename: Mamoru
authors.initials: M
authors.lastname: Takeda
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D009411:Nerve Endings / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology*; D011661:Pulmonary Stretch Receptors / Q000187:drug effects*; D011817:Rabbits; D012121:Respiration, Artificial; D012964:Sodium / Q000502:physiology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014628:Vagotomy; D014701:Veratridine / Q000494:pharmacology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D010042:Ouabain; D014701:Veratridine; D012964:Sodium; D013890:Thiourea; D009543:Nifedipine