Facilitatory role of NO in neural norepinephrine release in the rat kidney

Abstract

We examined modulation by nitric oxide (NO) of sympathetic neurotransmitter release and vasoconstriction in the isolated pump-perfused rat kidney. Electrical renal nerve stimulation (RNS; 1 and 2 Hz) increased renal perfusion pressure and renal norepinephrine (NE) efflux. Nonselective NO synthase (NOS) inhibitors [N(omega)-nitro-L-arginine methyl ester (L-NAME) or N(omega)-nitro-L-arginine], but not a selective neuronal NO synthase inhibitor (7-nitroindazole sodium salt), suppressed the NE efflux response and enhanced the perfusion pressure response. Pretreatment with L-arginine prevented the effects of L-NAME on the RNS-induced responses. 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), which eliminates NO by oxidizing it to NO(2), suppressed the NE efflux response, whereas the perfusion pressure response was less susceptible to carboxy-PTIO. 8-Bromoguanosine cGMP suppressed and a guanylate cyclase inhibitor [4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one] enhanced the RNS-induced perfusion pressure response, but neither of these drugs affected the NE efflux response. These results suggest that endogenous NO facilitates the NE release through cGMP-independent mechanisms, NO metabolites formed after NO(2) rather than NO itself counteract the vasoconstriction, and neuronal NOS does not contribute to these modulatory mechanisms in the sympathetic nervous system of the rat kidney.

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.…”

Nitric oxide: a co-modulator of efferent peptidergic neurosecretory cells including a unique octopaminergic neurone innervating locust heart

“…In mammals, NO can inhibit the biological activity of catecholamines (Macarthur et al 1995;Bruck et al 2001;Back et al 2002) and may either also inhibit (Barnes et al 2001) or facilitate (Tanioka et al 2002) their release. For example, neuronal NO exerts a well-documented negative chronotropic effect on the heart by reducing noradrenalin release from sympathetic nerve terminals (Schwarz et al 1995) and facilitating vagally induced bradycardia by increasing acetylcholine release from parasympathetic nerve endings (Mohan et al 2002; for a review, see Paton et al 2002).…”

Endothelial Dysfunction and Increased Responses to Renal Nerve Stimulation in Rat Kidneys during Rhabdomyolysis-Induced Acute Renal Failure: Role of Hydroxyl Radical

“…Among these mechanisms, NO was shown to facilitate NA release and NOS inhibition was shown to decrease NA release from sympathetic nerves in rat kidneys. 38 Since myoglobin scavenges NO, increased NA release from adrenergic nerves seems to be unlikely to explain increased vasoconstrictor response to RNS in our model. Although NOS inhibition was reported to decrease presynaptic NA release, RNS-induced vasoconstrictor responses were also shown to be increased in the same study.…”

“…Although NOS inhibition was reported to decrease presynaptic NA release, RNS-induced vasoconstrictor responses were also shown to be increased in the same study. 38 Additionally, endothelium denudation and guanylate cyclase inhibition were shown to increase sympathetic nerve stimulation-induced vasoconstriction in rabbit carotid arteries, 39 suggesting that endothelium and NO modulate sympathetic nerve stimulation responses and that increased RNS responses are due to endothelial dysfunction.…”