Amplifier function of resistance vessels and the left ventricle in hypertension.

We have recently modeled the structural factors responsible for the increased slope of the dose-vascular resistance response curves in the hindquarter bed under both in vitro and in vivo conditions. Slope increases when the ratio of wall thickness to internal radius (ri) increases and when ri decreases, but the slope decreases with greater wall stiffness. Enhanced slope is an indicator of the vascular amplifier properties. Resistance at maximum vasodilation in hypertension is also structurally determined converting enzyme inhibitors in spontaneously hypertensive rats (SHR) suggest that the reduction in ri can be reversed, suggesting that it is due to vascular hypertrophy. The concentrically hypertrophied left ventricle is an amplifier of stroke volume. Together, the vascular and left ventricular amplifiers contribute about 70% to the elevated total peripheral resistance in renovascular hypertension. In SHR, the vascular amplifier is present early in postnatal life before the onset of hypertension, which occurs in parallel with left ventricular hypertrophy (LVH). The development of the vascular amplifiers appears to be under the control of the renin-angiotensin system, whilst LVH appears to be under sympathoadrenal control, acting through cardiac alpha-adrenoceptors. Early immunosympathectomy plus prazosin treatment specifically prevents development of LVH in SHR and also prevents hypertension. In human hypertension, cardiac hypertrophy also plays an important role; after a period of prolonged therapy, the rate of redevelopment of hypertension when the drugs are stopped depends on the degree of regression of LVH during treatment. We conclude that the early development of vascular and cardiac amplifiers in primary hypertension appears to be genetically determined and the role of the heart in pathogenesis appears to be greater than previously thought.