TACHYCARDIA HEART-FAILURE ALTERS RABBIT AORTIC SMOOTH-MUSCLE RESPONSIVENESS TO ANGIOTENSIN-II

The effects of heart failure on the responsiveness of aortic smooth mu scle tissue to various vasoactive agents were examined. Heart failure was induced in rabbits by sustained rapid ventricular pacing (400 beat s/min) for 6-7 wk. After the rabbits were killed, strips of thoracic a orta were prepared and mounted in tissue baths. Responsiveness of thes e aortic strips to potassium depolarization and cumulative additions o f vasoactive agents was determined. Aortic strips from control and tac hycardia heart failure (THF) rabbits developed similar maximum forces to stimulation by potassium depolarization (0.77 +/- 0.08 vs. 0.96 +/- 0.16 kg/cm(2)), calcium chloride (0.71 +/- 0.09 vs. 0.88 +/- 0.06 kg/ cm(2)), and phenylephrine (0.90 +/- 0.08 vs. 1.14 +/- 0.09 kg/cm(2)). The maximum relaxation to isoproterenol was also unaffected by THF (0. 08 +/- 0.02 vs. 0.07 +/- 0.01 kg/cm(2)). In contrast, the maximum resp onse of aortic strips from THF rabbits to angiotensin II was significa ntly lower than control (0.37 +/- 0.07 vs. 0.069 +/- 0.09 kg/cm(2)). W ith regard to aortic smooth muscle sensitivity, no differences in the concentrations at which 50% of the maximal response is achieved (EC(50 )) were observed between THF and control strips for calcium chloride ( 0.10 +/- 0.01 vs. 0.16 +/- 0.04 mM), isoproterenol (51.5 +/- 13.5 vs. 51.0 +/- 5.4 nM), and phenylephrine (65.2 +/- 12.3 vs. 92.5 +/- 18.0 n M). However, THF was associated with a significant increase in the EC( 50) value for angiotensin II response (2.03 +/- 0.25 vs. 0.58 +/- 0.05 nM). These results demonstrate that THF is associated with a specific and significant reduction in the sensitivity and maximal responsivene ss of aortic smooth muscle to angiotensin II. THF-induced alterations in the characteristics of angiotensin II receptors may be responsible for these changes.