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Long-term administration of amlodipine prevents decompensation to diastolic heart failure in hypertensive rats

Nagahiro Nishikawa, MD^*, Tohru Masuyama, MD, PhD, FACC^*,*, Kazuhiro Yamamoto, MD, PhD, FACC^*, Yasushi Sakata, MD^*, Toshiaki Mano, MD, PhD^*, Takeshi Miwa, PhD, Motoaki Sugawara, PhD and Masatsugu Hori, MD, PhD, FACC^*

^* Department of Internal Medicine and Therapeutics (A8), Suita, Japan
Genome Information Research Center, Osaka University, Suita, Japan
Department of Cardiovascular Sciences, Tokyo Women’s Medical University, Tokyo, Japan

View larger version (17K): [in a new window]   Figure 1 Serial changes in systolic blood pressure in the control, diastolic heart failure (DHF), high-dose amlodipine (administered amlodipine of high dose [HDA]) and low-dose amlodipine (administered amlodipine of low dose [LDA]) rats. Data were obtained at the ages of 7, 13, 15, 17 and 19 weeks. Data are presented as the mean value ± SEM. *p < 0.05 vs. control group; #p < 0.05 vs. DHF group; p < 0.05 vs. high-dose amlodipine group at the same point.

View larger version (39K): [in a new window]   Figure 2 Hydroxyproline content of the left venticle (Pro-OH) and the ratio of type I to type III collagen mRNA levels (collagen I/III ratio) in the control, diastolic heart failure (DHF), high-dose amlodipine (administered amlodipine of high dose [HDA]) and low-dose amlodipine (administered amlodipine of low dose [LDA]) groups in the heart failure stage at 19 weeks (upper). *p < 0.05 vs. control group; #p < 0.05 vs. DHF group. The correlation between myocardial stiffness constant (MSC) and Pro-OH or the collagen I/III ratio was determined in pooled data taken from all of the rats (n = 22) (lower).

View larger version (161K): [in a new window]   Figure 3 Immunohistochemical staining of the myocardium from a Dahl-SS rat with type I collagen in the LV (control rat, upper left), an untreated rat (diastolic heart failure [DHF], upper right) and a rat treated with high-dose amlodipine ( administered amlodipine of high dose [HDA], lower left) and low-dose amlodipine (administered amlodipine of low dose [LDA]) at 19 weeks. An increase in type I collagen was observed in the DHF rat as compared with the control rat. A visible reduction in the level of type I collagen was noted in the order of the control, high-dose amlodipine and low-dose amlodipine rats.