Our principal objectives derive from our recent observation (1) and those of others that there exists a greater number of sympathetic nerves in blood vessels from the spontaneously hypertensive rat (SHR) during the established phase of hypertension. We intend (a) determining when the enhanced innervation occurs i.e. either during the normal period of innervation of blood vessels or at a time subsequent to innervation, (b) exploring the trophic factors responsible for sympathetic innervation in blood vessels from hypertensive and normotensive rats, and (c) establishing the relationship between hyper-noradrenergic innervation and the development of hypertension in this model. The techniques employed will include radioenzymatic assay of norepinephrine in blood vessels, bioassay for nerve growth factor, transplant and explant procedures, and the use of complimentary DNA probes for the measurement of messenger RNA for nerve growth factor. This is, to our knowledge, the first multidisciplinary study of its type, and it is consistent with our long term goals of understanding the function and development of vascular neuroeffector processes in normal and disease states. The relationship between the proposed studies and the clinical setting deserves comment. Based upon studies of identical twins and familial aggregation, the existence of genetic causative factors are evident in human essential hypertension just as they are in the SHR (2,3,4). Moreover, pioneering studies indicated that the basal blood pressure in humans has an important neurogenically maintained component (5); these findings are consistent with more recent studies that have demonstrated the existence of hyperadrenergic patients within the essential hypertensive population (6). Our study is designed to explore the relationship between molecular events that control the innervation of blood vessels and the development of hypertension in a genetic model of the disease. We hope the outcome of this study will provide a new basis from which to view the causes and development of hypertension in humans from the standpoint of genetic expression and cell regulation.
