Regulation of renin release is impaired after nitric oxide inhibition.
The aim of the present study was dual: first to establish that a preparation of afferent arterioles freshly isolated from the rat kidney is a suitable model to study renin release and synthesis, and second to investigate the effect(s) of nitric oxide (NO) inhibition on renin release in this model. Purification of renal microvessels was based on iron oxide infusion into the kidneys and separation of the afferent arterioles from glomeruli and connective tissue with a magnet. These microvessels express preprorenin mRNA, contain renin granules and release renin as evidenced by RT-PCR, immunocytochemistry and measurement of renin activity, respectively. Renin secretion was increased in isolated afferent arterioles after in vivo treatment with the diuretic furosemide (+300%) or in vitro treatment with the adenylyl cyclase activator forskolin (+50%), indicating that this vascular preparation responds appropriately to regulators of the renin-angiotensin system. Furthermore, in afferent arterioles isolated from control rats, renin release was positively correlated with total renin content (r = 0.85). In afferent arterioles isolated from rats chronically treated with the NO-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), forskolin was ineffective in modifying renin release despite stimulation of cAMP levels. In addition, the correlation between renin release and tissue renin content was disrupted. Similar results were obtained when cortical slices were used instead of afferent arterioles, suggesting that this defect in the regulation of renin release is independent of the presence of macula densa cells. To verify that the lack of regulation of renin release after L-NAME treatment was due to NO inhibition, the NO donor 3-morpholino-syndonimin-hydrochloride (SIN-1) was administered in afferent arterioles or cortical slices from kidneys of L-NAME-treated rats. In both preparations, SIN-1 reversed the L-NAME effect and re-established the responsiveness of renin release to forskolin and the relationship between renin release and renin content. These data indicate that the adenylyl cyclase-mediated mechanism regulating renin release is impaired when NO synthesis is inhibited.
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