ROLE OF SYMPATHETIC-NERVES FOR THE STIMULATION OF THE RENIN SYSTEM BYANGIOTENSIN-II RECEPTOR BLOCKADE

Objective To assess the relevance of sympathetic nerves for the stimul ation of renin secretion and renin gene expression during effective an giotensin II type 1 receptor blockade in vivo. Methods Male Sprague-Da wley rats were treated with the angiotensin II type 1-receptor blocker losartan (40 mg/kg) for 3 days. To examine the role of renal sympathe tic nerves in the stimulation of the renin system by losartan, left ki dneys were denervated 4 days prior to the treatment with losartan. Als o, to examine the role of circulating catecholamines in the stimulatio n of the renin system by losartan, the animals were administered a com bination treatment of losartan with the beta(1)-adrenoreceptor blocker metoprolol (50 mg/kg per day) for 3 days. Results Losartan treatment increased plasma renin activity about sevenfold and renal renin messen ger RNA (mRNA) levels about fivefold and decreased systolic blood pres sure from 118 to 95 mmHg. Administration of losartan elevated renin mR NA both in the innervated and in the denervated kidneys to the same le vel as it did in kidneys of normal animals. Losartan treatment increas ed plasma renin activity and renal renin mRNA levels in the beta(1)-bl ocker-treated rats to the same extent as it did in animals administere d losartan only. Conclusion These findings suggest that, under sub-chr onic treatment with hypotensive doses of angiotensin II receptor block ers, sympathetic outflow plays no important mediator role in the chara cteristic stimulation of renin secretion and renin gene expression, su ggesting that it is mainly a direct disinhibition of angiotensin II's action on the level of juxtaglomerular cells that accounts for the eff ect.