title: Presynaptic angiotensin II receptors and captopril-induced adrenergic transmission failure probably not via converting enzyme inhibition in guinea-pig pulmonary arteries.
abstract: This study aimed to clarify whether or not captopril modifies the activity of an intrinsic, presynaptic, angiotensin II receptor system within the vasculature in superfused spiral preparations of guinea-pig pulmonary arteries preloaded with 3H-norepinephrine. Angiotensins I and II dose-dependently facilitated 3H efflux and contraction evoked by transmural field stimulation at 5 Hz. A conversion rate of angiotensin I to angiotensin II calculated from the dose-response curves was 26.7 +/- 2.6%. 1Sar-8Ile-angiotensin II alone did not decrease the evoked 3H efflux and contraction, but antagonized the facilitation induced by angiotensins I and II. Captopril (1 and 10 mumol) inhibited the facilitation by angiotensin I but produced no effect on that by angiotensin II. Captopril alone at 1 mumol attenuated the evoked 3H efflux and contraction without decreasing contractile responses to exogenously applied norepinephrine, but the higher concentrations produced no further dose-dependent attenuation. Indomethacin alone produced no increases in the evoked 3H efflux. Captopril at 1 mumol still attenuated the evoked 3H efflux in the presence of indomethacin. On the other hand, enalaprilat alone (0.1-100 mumol) produced no effect on the evoked 3H efflux and contraction. Thus, in guinea-pig pulmonary arteries, angiotensin I is intramurally converted to angiotensin II, and there are presynaptic angiotensin II receptors to facilitate norepinephrine release. However, captopril-induced presynaptic adrenergic transmission failure appears to be dependent neither on an intrinsic angiotensin system nor on a prostaglandin-related mechanism.
authors.affiliation: Second Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Yasuda
authors.forename: H
authors.initials: H
authors.lastname: Shionoiri
authors.forename: T
authors.initials: T
authors.lastname: Kubo
authors.forename: Y
authors.initials: Y
authors.lastname: Misu
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D015773:Enalaprilat; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects*; D011945:Receptors, Angiotensin / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D004656:Enalapril; D002216:Captopril; D015773:Enalaprilat; D009638:Norepinephrine