Kazuo Umemura, Shinji Kikuchi, Yasuhiro Suzuki and Mitsuyoshi Nakashima
Department of Pharmacology, Hamamatsu University School of Medicine,
Hamamatsu 431-31, Japan
Abstract: Tranilast, N-(3,4-dimethoxycinnamoyl) anthranilic acid,
a widely used antiallergy drug in Japan, has been shown to inhibit transforming
growth factor-beta1 release from fibroblasts and reduce collagen
synthesis in keloid cells. In the present study, we have investigated the
effect of this drug on cardiac hypertrophy in spontaneously hypertensive
rats (SHR), with a focus on the cardiac collagen matrix, which is associated
with myocardial stiffness. Twenty-four-week-old SHRs and Wistar Kyoto rats
(WKYs) were administered tranilast (300 mg/kg) orally once a day for 4 weeks.
This treatment significantly suppressed increases in left ventricular collagen
concentration (P<0.05) and the left ventricular weight/body weights ratios
(P<0.05) in SHRs, and tranilast was ineffective on collagen concentration
and ventricular weight/body weights ratios in WKYs. Tranilast did not affect
systolic or diastolic blood pressure, end-diastolic left ventricular pressure
and heart rate in both SHRs and WKYs, and the agent did not change positive
dp/dt or cardiac output in SHRs. The pressure-volume relationship curve
was shifted to the left by the drug; the slope (k) of the logarithm of the
pressure-volume relationship curve was significantly increased (P<0.05)
in SHRs. It is concluded that the suppression of increases in cardiac collagen
and left ventricular mass by tranilast results in a corresponding prevention
of cardiac stiffness as studied in the SHR.
Keywords: Left ventricular hypertrophy, Tranilast, Cardiac collagen,
Myocardial stiffness, Spontaneously hypertensive rat