Effects of tetrandrine on cardiac and vascular remodeling.
Tetrandrine (Tet) is an alkaloid isolated from the Chinese herb Radix of Stephaniae tetrandrae S Moore. Cardiac and vascular remodeling confers a very definite risk of increased cardiovascular morbidity and mortality. Remodeling reversal has been achieved in human and experimental animals treated with some antihypertensive drugs but not all. This review will focus on cardiovascular remodeling and therapeutic effects of Tet. Three models, SHR, RHR (high renin), and DOCA-Salt HR (low renin) were used. Left ventricular and vascular remodeling had been developed in rats with 8-week untreated hypertension. Tet was administrated by ig 50 mg/kg/d for 9 weeks. Tet lowered SBP, left ventricular weight to body weight ratio, vascular media thickness, media to lumen ratio, cardiac and vascular wet weight, and collagen content. Tet decreased markedly the density and total number of dihydropyridine binding sites and also decreased Ca2+ overload in myocardium and vessels. Tet improved haemodynamic changes during remodeling special diastolic function such as LV compliance and stiffness, increased cardiac myosin ATPase activity and Na+-K+, Ca2+ ATPase activity, and normalized vascular reactivity. Tet inhibited proliferation of vascular smooth muscle cells, induced and sensitized VSMCs to pro-apoptosis stimulation, improved the endothelial function, and increased NO production. These results suggest that Tet was not only an anti-hypertensive drug but also an excellent drug to reverse cardiac and vascular remodeling.
Rao
Man-Ren
MR
Department of Cardiovascular Pharmacology, Nanjing Medical University, Nanjing 210029, China. Raomanren@263sina.com
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D044182:Benzylisoquinolines / Q000302:isolation & purification / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002319:Cardiovascular System / Q000187:drug effects*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000187:drug effects*
D000470:Alkaloids; D000959:Antihypertensive Agents; D044182:Benzylisoquinolines; C009438:tetrandrine; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium