Inhibitory effect of tranilast on hypertrophic collagen production in the spontaneously hypertensive rat heart.
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.
Umemura
K
K
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Kikuchi
S
S
Suzuki
Y
Y
Nakashima
M
M
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006332:Cardiomegaly / Q000378:metabolism* / Q000503:physiopathology; D003094:Collagen / Q000096:biosynthesis / Q000187:drug effects*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006909:Hydroxyproline / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D016277:Ventricular Function, Left / Q000187:drug effects; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D018926:Anti-Allergic Agents; D062367:ortho-Aminobenzoates; D003094:Collagen; C012293:tranilast; D006909:Hydroxyproline