Presynaptic angiotensin II receptors and captopril-induced adrenergic transmission failure probably not via converting enzyme inhibition in guinea-pig pulmonary arteries.
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.
Yasuda
G
G
Second Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Shionoiri
H
H
Kubo
T
T
Misu
Y
Y
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*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D004656:Enalapril; D002216:Captopril; D015773:Enalaprilat; D009638:Norepinephrine