Chronic effects of ANG II antagonist in heart failure: improvement of cGMP generation from ANP

The American Journal of Physiology
Y MaedaM Kinoshita

Abstract

To evaluate the effects of endogenous angiotensin II (ANG II) on the development of congestive heart failure (CHF), we examined cardiorenal and hormonal factors after chronic administration of the ANG II type 1 receptor antagonist TCV-116 in dogs with CHF induced by rapid right ventricular pacing. After 8 days of pacing, TCV-116 administration [1 (group 1) or 3 mg.kg-1.day-1 (group 2)] was started and continued until the 22nd day. TCV-116 was found to have protected the deterioration of cardiorenal functions and the activation of neurohormonal factors. Although there was no significant difference in the pulmonary capillary wedge pressure or plasma atrial natriuretic peptide (ANP) level between the TCV-116-treated groups (354 +/- 85 and 364 +/- 29 pg/ml for groups 1 and 2, respectively) and the vehicle group (385 +/- 20 pg/ml), the plasma guanosine 3',5'-cyclic monophosphate (cGMP) levels, a second messenger of ANP, were twofold higher in TCV-116-treated groups (49.4 +/- 10.2 and 50.6 +/- 7.7 pmol/ml for groups 1 and 2, respectively) than in the vehicle group (24 +/- 4.0 pmol/ml), with a high correlation between the plasma ANP and cGMP levels (r = 0.90; P < 0.05). These findings indicate that endogenous ANG II has important role...Continue Reading

Citations

Nov 19, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Kaoru FunabikiTakeshi Nakano

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