Endothelium–Derived Factors in Hypertensive Blood Vessels, Especially Nitric Oxide and Hypertension

Abstract

Endothelium–dependent relaxation (EDR) in the blood vessels of spontaneously hypertensive rats (SHR) and the role of nitric oxide (NO) in the initiation of hypertension are reviewed. EDR was impaired in blood vessels of SHR depending on age and degree of hypertension when compared with those of normotensive rats. The cause of the impairment varied among the type of blood vessels: a decrease in the production of NO and endothelium–derived relaxing factor (EDRF) and an increase in the production of endothelium–derived contracting factor (EDCF) are the main causes of the impairment in large arteries, while a decrease in endothelium–dependent hyperpolarization and increased release of EDCF are the main causes of the impairment in small arteries. Interactions among these endothelium–derived factors and changes in the interactions are also causes of impairment. Superoxide may be involved in the impairment of EDR by destroying NO. The endothelium depresses smooth muscle contraction, including spontaneous tone developed in vascular smooth muscle, and the depressing effect of the endothelium is impaired in the preparations from SHR. The endothelium of blood vessels of SHR are structurally injured as demonstrated by scanning electron microscopy. Antihypertensive treatment prevented these functional and structural changes. Chronic treatment with inhibitors of NO production in normotensive rats impaired EDR and elevated blood pressure. The impairment of EDR is a secondary change due to continued hypertension, and early initiation of antihypertensive therapy is recommended.