Resistance control in hypertension.

In hypertension the small arteries undergo structural changes that increase vascular resistance, both in vivo and in vitro. The hallmark of a physiological vascular amplifier is that enhanced resistance responses must occur about the resting value. For this to happen, the average radius of the resistance vessels must be narrower than normal; increased wall thickness without narrowing does not result in this type of amplification. In primary hypertension in spontaneously hypertensive rats (SHR), the structural changes in the resistance vessels precede the elevation in blood pressure. This is consistent with the hypothesis that these changes cause hypertension. The role of the sympathetic nervous system in early vascular development is unclear, in view of the absence of regression of amplifier properties in the hindlimb vessels after extensive immunosympathectomy. However, short periods of enalapril treatment in young animals attenuate the development of hypertension and normalize hindlimb resistance properties, suggesting that the renin-angiotensin system may have a role in early vascular growth. Studies in tissue culture suggest that both systems could play a role in smooth muscle growth, in conjunction with growth factors such as platelet-derived growth factor (PDGF)-like peptides and endothelin. The early structural change that occurs in hypertension is probably a variant of normal development of the resistance vasculature, with greater secretion of 'normal' growth factors and/or enhanced responsiveness of the vascular smooth muscle.