Renal nerves in the pathogenesis of hypertension in experimental animals and humans

R. E. Katholi Efferent renal innervation is composed of postganglionic sympathetic fibers to the renal arterioles, juxtaglomerular apparatus, and renal tubules. Increased efferent renal sympathetic nerve activity results in increased renal vascular resistance, renin release, and sodium retention. These responses from enhanced renal sympathetic activity contribute to normal cardiovascular homeostasis but could also facilitate the development of hypertension by shifting the arterial pressure-renal sodium excretion curve to the right. Accordingly, interruption of the renal nerves should prevent the development of hypertension in animal models in which increased sympathetic nervous system activity has been implicated. Renal denervation delays the development of hypertension and results in greater sodium excretion in the Okamoto and New Zealand spontaneously hypertensive rat and in the DOCA-salt-treated rat, suggesting that these responses are due, at least in part, to loss of efferent renal nerve activity. Similar sympathetically mediated renal vasoconstriction has been implicated in the pathogenesis of early essential hypertension in man. Recent studies indicate that the kidney is a sensory organ with mechano-receptive and chemoreceptive afferent renal nerves involved in renorenal and cardiovascular regulation. Renal denervation in established one-kidney one-clip and two-kidney one-clip Goldblatt hypertension in the rat and chronic coarctation in the dog results in an attenuation of the hypertension. The depressor effect of renal denervation in these models is not due to change in renin activity or sodium excretion but is associated with decreased activity of the sympathetic nervous system. These findings suggest that the afferent renal nerves contribute to the pathogenesis of renovascular hypertension by enhancing the activity of the sympathetic nervous system. The role of the afferent renal nerves in renovascular hypertension in humans warrants further study.