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When introduced clinically 6 years ago, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication. The initial two studies, SYMPLICITY HTN-1 and HTN-2, demonstrated great magnitudes of blood pressure reduction within 6 mo of the procedure and were based on a number of assumptions that may not have been true, including strict adherence to medication and absence of white-coat hypertension. The SYMPLICITY HTN-3 trial controlled for all possible factors believed to influence the outcome, including the addition of a sham arm, and ultimately proved the demise of the initial overly optimistic expectations. This trial yielded a much lower blood pressure reduction compared with the previous SYMPLICITY trials. Since its publication in 2014, there have been many analyses to try and understand what accounted for the differences. Of all the variables examined that could influence blood pressure outcomes, the extent of the denervation procedure was determined to be inadequate. Beyond this, the physiological mechanisms that account for the heterogeneous fall in arterial pressure following renal denervation remain unclear, and experimental studies indicate dependence on more than simply reduced renal sympathetic activity. These and other related issues are discussed in this paper. Our perspective is that renal denervation works if done properly and used in the appropriate patient population. New studies with new approaches and catheters and appropriate controls will be starting later this year to reassess the efficacy and safety of renal denervation in humans.

HALL,JOHN E., ARTHUR C. GUYTON,THOMAS E. JACKSON, THOMAS G. COLEMAN, THOMAS E. LOHMEIER, AND NICK C. TRIPPODO. Control of glomerular filtration rate by reninangiotensin system. Am. J. Physiol. 233(5): F366-F372, 1977 or Am. J. Physiol.: Renal Fluid Electrolyte Physiol. 2(5): F366-F372, 1977. -The role of the renin-angiotensin system (RAS) in autoregulating renal blood flow (RBF) and glomerular filtration rate (GFR) during reductions in renal artery pressure (RAP) was examined in the following groups of anesthetized dogs: group I, normal controls, n, 10; group II, normal dogs after intrarenal infusion of angiotensin II antagonist (AIIA), n, 7; group III, sodium-depleted controls, n, 7; group IV, sodium-depleted dogs after intrarenal infusion of AIIA, n, 10. In groups I and III, RBF and GFR did not change significantly between RAP’s of 85-127 mmHg, and decreased only 5-14% below control values at an RAP of approx. 70 mmHg. After AIIA in normal dogs (group II), RBF increased above control values when RAP was lowered; GFR remained relatively constant in group II as RAP was reduced to 85 mmHg, but decreased to 71 t 5% of the control value at 70 mmHg. After AIIA in sodium-depleted dogs (group IV), RBF autoregulation was well maintained, but GFR decreased progressively to 43 t 6% of the control value when RAP was reduced in steps to 70 mmHg. Although filtration fraction (FF) and calculated efferent arteriolar resistance in groups I and III remained relatively constant when RAP was reduced, in groups II and IV (in which the RAS was nonfunctional because of angiotensin II blockade) FF and efferent arteriolar resistance decreased progressively at all RAP’s below control. These observations are consistent with the hypothesis that the RAS plays an important role in controlling GFR through an efferent arteriolar constrictor mechanism, especially during high renin states such as sodium depletion.