Heptapeptide analogues induce greater blockade of renal than femoral vascular responses to angiotensin

We characterized blockade induced by 2 octapeptide and 2 heptapeptide analogues of angiotensin in the vascular beds of the kidney and hindlimb. Bolus injections of angiotensin II and its 1-des Asp analogue (angiotensin III) at the dose which reduced blood flow by about 50 percent and graded infusions of the analogue-antagonists were made directly into each artery and flow responses were measured with an electromagnetic flowmeter in the anesthetized dog. With the dose of antagonist which produced 50 percent inhibition of the control angiotensin response (ID 50) as the index, inhibition was slightly greater in the kidney than in the hindlimb for both the potent octapeptide antagonist {1-Sar, 8-Ala angiotensin II: kidney ID 50 = 15.3±1.7 (SD) ng/kg/min; hindlimb ID 50 = 23.3±1.8 (SD) ng/kg/min} and the weak octapeptide antagonist {1-D-Asn, 8-Ala angiotensin II: kidney ID 50 = 178.7±2.0 (SD) ng/kg/min; hindlimb ID 50 = 266.7±1.9 (SD) ng/kg/min}. In contrast, both the potent and weak heptapeptide analogues were much more effective as antagonists in the renal than the femoral vascular bed {1-des Asp, 8-Ile AII: kidney ID 50 = 14.9±1.8 (SD) ng/kg/min; hindlimb ID 50 = 36.2±1.9 (SD) ng/kg/min}; {1-des Asp, 8-Ala angiotensin II: kidney ID 50 = 408.9±1.8 (SD) ng/kg/min; hindlimb ID 50 = 1270±2.8 (SD) ng/kg/min}. The difference in the influence of the analogues in the two vascular beds may reflect either a difference in their angiotensin receptors or in the rate at which heptapeptide analogues are degraded in their transit through the renal and femoral vasculature.