Endogenous Opioids and Reversal of Renovascular Hypertension

The rapid fall in blood pressure after removal of the constricting clip in two-kidney one-clip hypertension in rats has been well demonstrated [1–3] although the precise mechanism is still not fully understood. Studies on the hemodynamic effects of unclipping suggest that this fall is due to the lowering of total peripheral resistance [4, 5] that occurs while hypertensive structural changes are still present [6], thus implying that vessel tone has become subnormal. Surgical reversal during pharmacological inhibition of the renin-angiotensin system indicated that this pressor mechanism was not fully responsible for the maintenance, or its suppression, of the reversal of this form of hypertension [3]. Sodium retention does not appear to be responsible for the elevated blood pressure [1, 2]. The role of changes in the activity of the sympathetic nervous system in the maintenance of the elevated blood pressure and in its surgical reversal is more controversial [7, 8]. Attention therefore has been directed to possible vasodepressor mechanisms. It is therefore of interest that a recent study has postulated that compounds released in the renal venous effluent after unclipping suppressed tonic efferent sympathetic nervous system activity and also had and effect on behavior, consistent with a central opiate-like action [9]. In other studies, induction of hypertension in the two-kidney one-clip model was associated with altered activity of the endogenous opioid system [10]. Endogenous opioids have been shown to have profound cardiovascular effects in other pathophysiological states [11–13]. In addition to hemodynamic changes invoked by unclipping, cardiovascular effects of any anesthetic used during this procedure will contribute to the initial rapid fall in blood pressure, and therefore obfuscate the true time course of the reversal of hypertension.