Endothelium-dependent regulation of resistance arteries: alterations with aging and hypertension

Small arteries with a diameter of 200 microns or less play an important role in the regulation of peripheral vascular resistance. Dysregulation of vascular tone of these arteries may contribute significantly to high blood pressure. The contractile state of blood vessels is regulated by peripheral neurons, vascular smooth muscle, and the endothelium. In perfused mesenteric resistance arteries of the rat, removal of the endothelium markedly augments the sensitivity and maximal response to norepinephrine and endothelin-1. Acetylcholine causes profound endothelium-dependent relaxation of resistance arteries contracted with norepinephrine or endothelin-1. The potency of the muscarinic agonist is particularly pronounced with intraluminal application. The inhibitory effects of the endothelium against contractions induced by norepinephrine and endothelin-1 are reduced with aging and hypertension. The endothelium-dependent relaxation in response to intraluminal, but not extraluminal, acetylcholine is blunted in mesenteric resistance arteries of hypertensive rats and in the forearm circulation of hypertensive patients studied in vivo. The sensitivity of vascular smooth muscle to the effects of endothelin decreases with advancing age and in the spontaneously hypertensive rat. Thus, endothelium-derived vasoactive substances can profoundly affect vascular tone of resistance arteries studied in vitro and in vivo. The inhibitory effects of the endothelium against vasoconstrictor stimuli decreases with aging and hypertension, indicating a dysfunction of these regulatory mechanisms under these conditions.