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Zinc-finger nucleases (ZFNs) drive efficient genome editing by introducing a double-strand break into the targeted gene. Cleavage is induced when two custom-designed ZFNs heterodimerize upon binding DNA to form a catalytically active nuclease complex. The importance of this dimerization event for subsequent cleavage activity has stimulated efforts to(More)
The present studies in perfused specimens of the juxtaglomerular apparatus microdissected from rabbit kidneys were performed to quantitatively evaluate the relation between macula densa NaCl concentration and renin secretion and to study the effect of furosemide and verapamil on NaCl dependency of renin release. Renin secretion was found to decrease(More)
To examine the possible role of NO in macula densa control of renin secretion, we examined the effects of varying NO availability on renin release in the isolated perfused rabbit juxtaglomerular apparatus (JGA). Gradual increments of luminal Na/Cl concentration ratio (mM/mM) from 26/7 over 46/27, 66/47, to 86/67 caused a progressive decrease in renin(More)
The purpose of the present studies was to evaluate directly the role of prostaglandins in macula densa-mediated renin release. Individual juxtaglomerular apparatus specimens were microdissected from rabbit kidney and perfused with a solution containing either high NaCl (Na+ = 141 meq/l; Cl- = 122 meq/l) or low NaCl (Na+ = 26 meq/l; Cl- = 7 meq/l)(More)
Experiments were performed on juxtaglomerular granular cells (JGC) in short-term primary culture to determine the direct immediate effect of NO on renin secretion and to test whether JGC are able to generate NO. Renin secretion was measured repeatedly over short time intervals in a cell superfusion system. Renin release did not significantly decrease over a(More)
Evidence that the renal sympathetic nerves have direct effects on renal tubular function suggests that neurogenic mechanisms may play an important role in the daily regulation of sodium balance. We evaluated the influence of the renal nerves on the rate of elevating urinary sodium excretion (UNaV) after a step increase in fixed sodium intake. Conscious rats(More)
Many questions remain concerning the precise mechanism by which the luminal signal for renin secretion is transmitted from the MD to the JG granular cell. It appears likely that a number of pathways may participate in MD-mediated changes in renin release, some of the agents serving to modulate release, others participating directly in signal transmission.(More)
INTRODUCTION The spontaneously hypertensive rat (SHR) has been shown to possess elevated efferent sympathetic nerve activity, and renal denervation delays the development of hypertension in this genetic strain. Evidence that the renal sympathetic nerves have direct effects on tubular function suggests that one of the mechanisms for increasing arterial(More)
The spontaneously hypertensive rat (SHR) has an elevated efferent sympathetic nerve activity, suggesting that the renal handling of sodium and water may be altered. This study evaluated the renal neurogenic influence on the rate of achieving sodium balance in adult SHRs and Wistar-Kyoto (WKY) rats after either a step increase or step decrease in fixed(More)
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