ANALYSIS OF RESPONSES TO ANGIOTENSIN-IV IN THE PULMONARY VASCULAR BEDOF THE CAT

Responses to angiotensin IV were investigated and compared with respon ses to angiotensin II in the pulmonary vascular bed of the intact-ches t cat under constant flow conditions. Under low resting tone condition s, intralobar injections of angiotensin IV caused dose-related increas es in lobar arterial pressure. Angiotensin II also increased lobar art erial pressure and was 100 fold more potent than angiotensin IV. Dose- response curves for both peptides were parallel, and the time-to-peak increase in lobar arterial pressure in response to angiotensin IV and angiotensin II was similar whereas the duration of the response to ang iotensin IV was significantly shorter. Following administration of the angiotensin receptor subtype 1 (AT(1)) antagonist, DuP 532 (2-n-butyl -4-chloro-5-hydroxymethyl-1- 1H-tetrazol-5-yl)biphenyl-4-yl)-methyl]im idazole), responses to angiotensin IV and angiotensin II were reduced in a similar manner, whereas pulmonary presser responses to serotonin were not altered. In contrast to the inhibitory effects of the angiote nsin AT(1) receptor antagonist, administration of PD 123,319 ((S)-1-[[ 4-(dimethyl-amino)-3-methyl-phenyl] henylacetyl)-4,5,6,7-tetrahydro-1H -imidazol[4,5-c] pyridine-6-carboxylic acid), an angiotensin AT(2) rec eptor antagonist, did not change responses to angiotensin II and angio tensin IV. The results of the present study demonstrate that angiotens in IV has significant vasoconstrictor activity in the pulmonary vascul ar bed, and suggest that presser responses to angiotensin IV are media ted by the activation of angiotensin AT(1) receptors. These data indic ate that angiotensin IV is 100-fold less potent than angiotensin II an d suggest that the hexapeptide may have a lower apparent affinity for the angiotensin AT(1) receptor than does angiotensin II in the pulmona ry vascular bed of the cat.