ANALYSIS OF RESPONSES TO ANGIOTENSIN PEPTIDES IN THE HINDQUARTERS VASCULAR BED OF THE CAT

Responses to angiotensin I, II, III, and IV, des-Asp(1)-angiotensin I, and (p-amino-Phe(6))-angiotensin II were compared in the hindquarters vascular bed of the cat. The peptides produced dose-related increases in perfusion pressure, and dose-response curves to all six peptides w ere parallel. Des-Asp(1)-angiotensin I, angiotensin I, II, and III pro duced similar increases in perfusion pressure and were similar to 300- fold more potent than (p-amino-Phe(6))-angiotensin II, 100-fold more p otent than angiotensin IV, 30-fold more potent than norepinephrine, an d 10-fold more potent than U-46619. The time courses of the response t o des-Asp(1)-angiotensin I, angiotensin I, II, and III were similar, a nd responses were not altered by a time-delay coil. DuP-532, an AT(1) receptor antagonist, reduced responses to the six angiotensin peptides . PD-123,319 did not alter responses to the angiotensin peptides. The angiotensin-converting enzyme inhibitor captopril reduced responses to angiotensin I and des-Asp(1)-angiotensin I. These results show that d es-Asp(1)-angiotensin I as well as angiotensin I, II, III, and IV have similar efficacy and that responses to the peptides and (p-amino-Phe( 6))-angiotensin II are mediated by AT(1) receptors. These results sugg est that AT(2) receptors have little role in modulating responses and that angiotensin IV has a lower affinity for the AT(1) receptor than d oes angiotensin II or III. The results also indicate that complete rap id local conversion of the substrates into active peptides occurs near the site of action within the hindquarters vascular bed.