EFFECTS OF DES-ASP-ANGIOTENSIN-I ON THE ELECTRICALLY STIMULATED CONTRACTION OF THE RABBIT PULMONARY-ARTERY

In the presence of 3 x 10(-6) M captopril, 5 x 10(-7) M des-Asp-angiotensin I was found to inhibit the electrically (1 and 2 Hz) induced contraction of the rabbit pulmonary artery but had no significant effect on the noradrenaline-stimulated contraction. 2.8 x 10(-6) M indomethacin and 10(-6) M losartan but not 10(-6) M (S) 1-{[4-(dimethylamino)-3-methylphenyl]methyl}-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo-1H-imidazo[4,5-c]pyridine-6-carboxylic acid, ditrifluoroacetate, dihydrate (PD123319) attenuated the inhibition. The inhibition of the electrically stimulated contraction by 5 x 10(-7) M des-Asp-angiotensin I coincided with a significant drop in the accompanying evoked H-3 overflow from re-uptaken [H-3]noradrenaline. The results indicate that des-Asp-angiotensin I acts presynaptically on a subtype of angiotensin receptor that involves the release of prostaglandin(s). In addition, this receptor subtype is susceptible to blockade by angiotensin AT(1)- but not AT(2)-specific receptor antagonists. It was suggested that this receptor subtype is identifiable with the recently described angiotensin AT(1B) receptor subtype found in the brain, pituitary and adrenal glomerulosa. These findings demonstrated a direct action of sub-micromolar concentrations of des-Asp-angiotensin I on a blood vessel and indicate that the nonapeptide is an active angiotensin per se.