Hypernoradrenergic innervation: its relationship to functional and hyperplastic changes in the vasculature of the...

There is now compelling evidence indicating that there is a greater sympathetic innervation of blood vessels in the spontaneously hypertensive rat (SHR) when compared with the innervation of corresponding vessels in the normotensive genetic control rat (WKY). In selected vascular beds in the SHR, increased sympathetic innervation occurs immediately after birth and prior to the expression of hypertension in the animal. In contrast, the available evidence suggests that the sympathetic innervation of cardiac tissue in SHR and WKY are similar in young and adult rats. The functional significance of the enhanced sympathetic innervation of blood vessels in the SHR with regard to the development or maintenance of hypertension relates in two ways to the well-established phenomena of vascular smooth muscle cell hypertrophy and hyperplasia, which are thought to be the pathophysiological basis for the increased peripheral vascular resistance and elevated blood pressure in this animal model of hypertension. First, the enhanced innervation of blood vessels in the SHR leads to an augmented release of the vasoconstrictor transmitter noradrenaline (NA). The predicted consequences of this augmented release of NA upon vascular contraction are modulated by the presence of a larger number of sites for neuronal inactivation (i.e. reuptake sites) of NA by virtue of the presence of the increased innervation. Second, and of more significance, is the inter-relationship between hypernoradrenergic innervation and vascular smooth muscle hyperplasia, as the early appearance of such changes is a powerful indicator for the subsequent expression of hypertension in the SHR. In view of the substantial evidence that implicates vascular smooth muscle cells in regulating the degree of their sympathetic innervation and confirms the influence of sympathetic nerves upon vascular smooth muscle hyperplastic change, attention is drawn to the role of trophic factors in providing the setting for the development of hypertension in the SHR.