Effects of tetrandrine on cardiac and vascular remodeling.
Abstract
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.
Keywords:
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.