The sympathetic nervous system in clinical and experimental hypertension.

In summary, many lines of evidence indicate that the sympathetic nervous system, via the renal nerves, plays an important role in the pathogenesis of renovascular hypertension in humans and laboratory animals. Patients with established renovascular hypertension have increased sympathetic nervous system activity, as evidenced by increased plasma and urinary norepinephrine levels, elevated excretion of catecholamine metabolites, and an exaggerated depressor response to centrally acting sympatholytic agents. The observation that converting enzyme inhibitors can cause both blood pressure and urinary norepinephrine excretion to return to normal in patients with renovascular hypertension is consistent with the interpretation that activation of the sympathetic nervous system in these subjects is, at least in part, angiotensin-induced. The sympathetic nervous system, via the efferent renal nerves, plays a role in the pathogenesis of hypertension in a number of experimental models. In the spontaneously hypertensive rat of the Okamoto strain (SHR) and in the DOCA/NaCl hypertensive model, increased renal efferent nerve activity contributes to the development of hypertension by causing increased renal sodium retention. In both of these experimental models, renal denervation delays the development and blunts the severity of hypertension. This delay is associated with increased urinary sodium excretion, suggesting a renal efferent mechanism. In contrast to the predominantly efferent renal nerve mechanisms observed in the DOCA-NaCl and SHR models, studies of the effects of renal denervation in one-kidney, one-clip and two-kidney, one-clip Goldblatt hypertensive rats suggest that renal afferent nerves are important in these models of hypertension. Total renal denervation in rats with established 1K, 1C and 2K, 1C hypertension attenuates the severity of the hypertension without altering sodium intake or excretion, renin activity, water intake, or renal function. Thus, efferent renal nerve activity does not appear to be involved in the development of maintenance of 1K, 1C or 2K, 1C hypertension. In contrast with the findings in SHR and DOCA-NaCl rats, these studies provide indirect evidence that the renal afferent nerves play a role in the pathogenesis of this form of experimental hypertension. The major effect of renal denervation in these models appears to be an interruption of renal afferent nerve activity, which by a direct feedback mechanism attenuates systemic sympathetic tone, thereby lowering blood pressure.(ABSTRACT TRUNCATED AT 400 WORDS)