Factors predicting the blood pressure response to renal denervation: Insights from experimental animals

My lab has studied the effects of surgical renal denervation (RDN) on blood pressure (BP) in rats with established hypertension. Among the models we investigated, we found that RDN caused the most predictable and sustained fall in BP in older SHR (>9 month old). Because it is apparent that humans with hypertension exhibit quite variable responses to RDN, and no reliable predictor of BP response (except initial pre-treatment BP) has been identified to date, we used this experimental paradigm to investigate factors that might predict a larger BP response to RDN. Higher pre-RDN BP and higher “resting” sympathetic activity (indexed from plasma norepinephrine) were weak predictors of a larger BP response to RDN. The thoroughness of denervation (indexed from kidney norepinephrine content) was a strong predictor of BP response. Since all human patients subjected to RDN are taking antihypertensive drugs, we also determined if prior antihypertensive treatment with various drugs would modify the BP response to subsequent RDN. The following drugs were found not to significantly affect the BP response to RDN: hydralazine, amlodipine, enalapril, losartan, hydrochlorothiazide, and furosemide. On the other hand, pretreatment with the centrally acting sympatholytic drug clonidine completely eliminated the BP response to RDN. Likewise, pretreatment with the beta-1 adrenergic receptor blocker atenolol prevented a sustained fall in BP in response to RDN in our model. Together these results indicate that there may be identifiable factors that can be used in the clinical setting to predict the BP response to RDN. The results also suggest that a valid assessment of renal nerve ablation as a therapy in human patients will require careful confirmation of the extent, and duration, of denervation.