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Am J Physiol Heart Circ Physiol 280: H1853-H1860, 2001;
0363-6135/01 $5.00
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Vol. 280, Issue 4, H1853-H1860, April 2001

The role of ANG II and endothelin-1 in exercise-induced diastolic dysfunction in heart failure

Che-Ping Cheng, Tomohiko Ukai, Katsuya Onishi, Nobuyuki Ohte, Makoto Suzuki, Zhu-Shan Zhang, Heng-Jie Cheng, Hideo Tachibana, Akihiko Igawa, and William C. Little

Cardiology Section, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1045

The diastolic dysfunction present at rest in congestive heart failure (CHF) is exacerbated during exercise (Ex). Increases in circulating ANG II and endothelin-1 (ET-1) during Ex may contribute to this response. We assessed the effect of Ex on circulating plasma levels of ANG II and ET-1 and left ventricular (LV) dynamics before and after pacing-induced CHF at rest and during Ex in nine conscious, instrumented dogs. Before CHF, there were modest increases in circulating levels of ANG II (but not ET-1) during Ex. LV diastolic performance was enhanced during Ex with decreases in the time constant of LV relaxation (tau ), LV end-systolic volume (VES), and LV minimum pressure with a downward shift of the LV early diastolic portion of the pressure-volume (P-V) loop. This produced an increase in peak LV filling rate without an increase in mean left atrial (LA) pressure. After CHF, the resting values of ANG II and ET-1 were elevated and increased to very high levels during Ex. After CHF, mean LA pressure, tau , and LV minimum pressure were elevated at rest and increased further during Ex. Treatment with L-754,142, a potent ET-1 antagonist, or losartan, an ANG II AT1-receptor blocker, decreased these abnormal Ex responses in CHF more effectively than an equally vasodilatory dose of sodium nitroprusside. Combined treatment with both ANG II- and ET-1-receptor blockers was more effective than either agent alone. We conclude that in CHF, circulating ANG II and ET-1 increase to very high levels during Ex and exacerbate the diastolic dysfunction present at rest.

relaxation; left ventricle filling; nitroprusside; congestive heart failure; angiotensin II


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