Tachycardia heart failure alters rabbit aortic smooth muscle responsiveness to angiotensin II.
The effects of heart failure on the responsiveness of aortic smooth muscle tissue to various vasoactive agents were examined. Heart failure was induced in rabbits by sustained rapid ventricular pacing (400 beats/min) for 6-7 wk. After the rabbits were killed, strips of thoracic aorta were prepared and mounted in tissue baths. Responsiveness of these aortic strips to potassium depolarization and cumulative additions of vasoactive agents was determined. Aortic strips from control and tachycardia heart failure (THF) rabbits developed similar maximum forces to stimulation by potassium depolarization (0.77 +/- 0.08 vs. 0.96 +/- 0.16 kg/cm2), calcium chloride (0.71 +/- 0.09 vs. 0.88 +/- 0.06 kg/cm2), and phenylephrine (0.90 +/- 0.08 vs. 1.14 +/- 0.09 kg/cm2). The maximum relaxation to isoproterenol was also unaffected by THF (0.08 +/- 0.02 vs. 0.07 +/- 0.01 kg/cm2). In contrast, the maximum response of aortic strips from THF rabbits to angiotensin II was significantly lower than control (0.37 +/- 0.07 vs. 0.069 +/- 0.09 kg/cm2). With regard to aortic smooth muscle sensitivity, no differences in the concentrations at which 50% of the maximal response is achieved (EC50) 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 nM). However, THF was associated with a significant increase in the EC50 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 responsiveness of aortic smooth muscle to angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
Porsa
E
E
Department of Medicine, University of Texas Health Science Center at San Antonio.
Freeman
G L
GL
Herlihy
J T
JT
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology; D002303:Cardiac Output, Low / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D013610:Tachycardia / Q000150:complications*
D000804:Angiotensin II; D010656:Phenylephrine; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium