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

Abstract

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 renin-angiotensin system, so we determined whether this treatment modality alters renal excretory function in rabbits with renovascular hypertension. 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. 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. 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.