Effects of chronic sympatho-inhibition on renal excretory function in renovascular hypertension

Abstract

Objective Treatment of renovascular hypertension with drugs that directly target the renin-angiotensin system may compromise glomerular filtration and renal excretory function, leading to renal failure. Centrally acting sympathoinhibitory agents also inhibit the reninangiotensin system, so we determined whether this treatment modality alters renal excretory function in rabbits with renovascular hypertension.Methods Rabbits were equipped with bilateral renal artery flow probes and a renal nerve electrode. Hypertension was induced with a renal artery clip (2K1C) or rabbits were sham-clipped. After 2 weeks, a subcutaneous minipump was implanted to deliver rilmenidine (2.5 mg/kg per day) or vehicle for 3 weeks. Haemodynamic variables and renal function were studied under control conditions and during intravenous infusion of isotonic saline (154 mmol/l NaCl) at increasing rates of 4, 12 and 36 ml/kg per hour.Results Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were greater in 2K1C rabbits than sham-clipped rabbits, but total urine flow, sodium excretion and glomerular filtration rate were similar in the two groups. In 2K1C rabbits, rilmenidine reduced MAP to close to control levels and reduced RSNA (40%), but did not significantly alter basal renal blood flow, glomerular filtration rate, urine flow or sodium excretion. The natriuretic response to isotonic saline load in 2K1C rabbits was not significantly altered by rilmenidine.Conclusion These observations show that chronic treatment of rabbits with renal artery stenosis with a centrally acting sympathoinhibitory agent, despite normalizing MAP, does not compromise renal excretory function. Thus, this treatment modality may be particularly useful in renovascular hypertension. J Hypertens 29:945-952 Q 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Journal of Hypertension 2011, 29:945-952

Role of Renal Nerves in the Treatment of Renovascular Hypertensive Rats withL-Arginine

“…Increases in efferent RSNA reduce RBF and urinary sodium excretion by activating α 1-adrenoceptors [ 37 ]. Burke et al demonstrated that the kidney function appears to be well preserved in animals that have had one kidney clipped and the blood pressure normalized by sympathetic inhibition [ 38 ]. Franquini et al [ 39 ] demonstrated that renal denervation induced an increase in urine volume and sodium excretion.…”

Renal sympathetic activation from long-term low-dose angiotensin II infusion in rabbits

“…Thus circulating angiotensin II (AngII) has been proposed as a major signal to the central nervous system (CNS) contributing to the neurogenic component in hypertension [16][17][18]. Indeed, using a rabbit model of renovascular hypertension (2K1C), we found that inhibition of the SNS with chronic rilmenidine restored BP to normal levels without impairing renal function and markedly reduced plasma renin levels, suggesting that the renal sympathetic nerve activity (RSNA) contributes to the hypertension through the release of renin [19,20].…”

Renal Deafferentation Prevents Progression of Hypertension and Changes to Sympathetic Reflexes in a Rabbit Model of Chronic Kidney Disease

“…GFR was measured using an intravenous infusion of [ 14 C]inulin (1036 Bq/kg per minute, Perkin Elmer Life Sciences, Boston, MA) to calculate inulin clearance. 20 Total norepinephrine spillover to plasma was measured with arterial blood samples taken before and at 40, 50, and 60 minutes after starting an intravenous infusion of [ 3 H]norepinephrine (4070 Bq/kg per minute, Perkin Elmer). 11 At the end of the experiment, rabbits were euthanized and the left kidney and ventricle removed, weighed, and frozen at −80 °C.…”