Nitric Oxide Modulation of Neurally Induced Proximal Tubular Fluid Reabsorption in the Rat

Abstract

Abstract-This study investigated the role of NO in mediating the renal sympathetic nerve-mediated increases in proximal tubular fluid reabsorption (Jva). In inactin-anesthetized Wistar rats, renal sympathetic nerve stimulation (15 V, 2 ms) at 0.75 and 1.0 Hz did not change blood pressure or glomerular filtration rate but did decrease urine flow and sodium excretion in a frequency-related fashion by 40% to 50% at 1.0 Hz (both, PϽ0.01). Renal nerve stimulation in control animals increased Jva by 11% at 0.75 Hz (PϽ0.05) and 31% at 1.0 Hz (PϽ0.01). Intraluminal N-nitro-L-arginine methyl ester (L-NAME) resulted in a higher basal Jva (19%, PϽ0.05), and renal nerve stimulation had no effect on Jva. When L-NAME plus sodium nitroprusside was present intraluminally, however, there were frequency-dependent increases in Jva that were similar in pattern and magnitude to the control rats. Introduction of the relatively selective nNOS blocker 7-nitroindazole intraluminally, at 10 Ϫ6 and 10 Ϫ4 M, raised basal Jva by 18% and 24%, respectively (PϽ0.01), and renal nerve stimulation did not change Jva. Intraluminal aminoguanidine (10 Ϫ4 M), a relatively selective iNOS blocker, did not affect basal Jva, which remained unchanged during renal nerve stimulation. These data are consistent with NO exerting a tonic inhibitory action on the basal levels of Jva, which, in part, is caused by NO generated by the nNOS isoform. Moreover, the findings have revealed that the presence of NO is necessary to ensure that renal nerves can stimulate fluid reabsorption by the proximal tubules, requiring NO generated from both nNOS and iNOS. Key Words: nitric oxide Ⅲ renal nerves Ⅲ antinatriuresis Ⅲ sodium Ⅲ kidney T he renal sympathetic nerves play an important role in regulating renin release, tubular sodium and water reabsorption, and renal vascular resistance. Increasing levels of renal nerve activity progressively recruit these functions; that is, at low frequencies there is renin release. Thereafter, increased tubular reabsorption of fluid becomes apparent, and it is only at the higher frequencies that there are reductions in renal blood flow and glomerular filtration rate. 1,2 Noradrenaline is released from the renal sympathetic nerve endings and, as at other sympathetic neuroeffector junctions, has an autoinhibitory feedback action, mediated via presynaptic ␣ 2 -adrenoceptors, to attenuate the level of neurotransmitter release. 3 At the postsynaptic level, noradrenaline acts on the ␣ 1 -adrenoceptors of the epithelial cells to stimulate sodium, and hence water, transport by activation of the Na ϩ /K ϩ -ATPase at the basolateral membrane and the Na ϩ /H ϩ -exchanger at the apical membrane. 4,5 Recently, there has been increasing interest in the role of NO in the control of renal function. NO synthase (NOS) catalyzes the generation of NO, which stimulates cyclic GMP production to modify specific aspects of renal function. 6 At least 3 isoforms of NOS have been identified so far: inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS),...

Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

“…Thus ANG II stimulates neuronal NOS and renal interstitial cGMP production, probably via the AT 2 receptor (52), and recent work by Zhang and Mayeux (65) shows that neuronal NOS-derived NO is triggered beyond a certain ANG II threshold concentration, thereby counteracting the stimulatory effect on the Na-K-ATPase. Similarly, studies have shown that NO exerts a tonic inhibitory action on nervemediated proximal tubular reabsorption, and at the same time NO exerts a facilitatory role in norepinephrine release (55,61,62). Altogether these experiments show that NO is an integrated modulating agent in renal proximal tubular function, further studies on the interaction between the NO system and other modulators of proximal tubular sodium handling in cirrhosis are warranted.…”

Discoordinate regulation of renal nitric oxide synthase isoforms in ovariectomized mRen2.Lewis rats

“…Several reports implicate a role for nNOS to attenuate tubuloglomeruler feedback (TGF) (36,43); however, one would expect an increase in blood pressure due to an enhanced TGF response following nNOS inhibition. Johns and colleagues (4,44) found that nNOS inhibition attenuated the response of renal nerve stimulation on sodium excretion, suggesting a facilitory role for NO on adrenergic release. In this regard, Cervenka et al (8) demonstrated increased sodium excretion following acute nNOS inhibition in intact but not denervated male mRen(2)27 rats, the founder strain to the current congenic strain.…”

Redox Control of Renal Function and Hypertension

“…Interestingly, NO has bidirectional roles in mediating or modulating renal sympathetic nerve action. In the proximal tubules, it may mediate the sodium-retaining effects of sympathetic nerves (370), whereas it may blunt the neural effects in isolated perfused rat kidney and in the renal medulla (62,266).…”