Renal Denervation Prevents Intraglomerular Platelet Aggregation and Glomerular Injury Induced by Chronic Inhibition of Nitric Oxide Synthesis

Abstract

Nitric oxide (NO) inhibits platelet adhesion and aggregation in vitro. In vivo, chronic inhibition of NO synthesis induces nephrosclerosis and hypertension. Although the pathophysiological mechanism of this glomerular injury has not been clarified, sympathetic nerve activation, a potent procoagulant stimulus elicited by NO inhibition, may play a role. To investigate the role of renal sympathetic nerves in the development of renal injury induced by N^G-nitro-L-arginine methyl ester (L-NAME), a specific NO synthesis inhibitor, we examined renal histological changes in four groups of Sprague-Dawley rats: (1) sham operated, vehicle treated; (2) sham operated, L-NAME treated; (3) denervated, vehicle treated, and (4) denervated, L-NAME treated. Following renal denervation or sham operation, L-NAME was administered orally for 4 weeks. Chronic NO inhibition induced platelet aggregation and erythrocyte stasis in the glomerular capillary lumen accompanied by electron-microscopic glomerular injury. Renal denervation abrogated platelet aggregation and glomerular injury in L-NAME-treated animals. Thus, chronic NO synthesis inhibition induced intraglomerular platelet aggregation and glomerular injury, which was attenuated by renal nerve denervation. These results suggest that intrinsic NO may have an antithrombotic effect in the glomeruli and may play a protective role in the progression of glomerular injury possibly mediated by renal sympathetic nerves.

Renal Denervation Promotes Atherosclerosis in Hypertensive Apolipoprotein E-Deficient Mice Infused with Angiotensin II

“…Five days later, mice were euthanized and norepinephrine content in the kidney was determined. RDN significantly decreased the median norepinephrine content in the kidney by 93.4% ( P = 0.003, Figure 2A), which is similar to the previously reported ability of RDN to decrease norepinephrine content by 95% (Nakashima et al, 1996), suggesting that the RDN procedure was successful.…”

Renal Sympathetic Denervation Suppresses De Novo Podocyte Injury and Albuminuria in Rats With Aortic Regurgitation

“…In protocol 2, the rats underwent UNX and RDX under anesthesia with sodium pentobarbital (50 mg/kg, i.p.). Complete RDX was achieved by cutting all of the visible renal nerves from the renal artery and vein, and painting these vessels with a solution of 10% phenol in ethanol 13 . This method ablates the afferent and efferent renal nerves 13, 20 .…”

“…Complete RDX was achieved by cutting all of the visible renal nerves from the renal artery and vein, and painting these vessels with a solution of 10% phenol in ethanol 13 . This method ablates the afferent and efferent renal nerves 13, 20 . After sacrificing the rats, renal tissue NE content was measured to confirm the completeness of RDX 13, 20 .…”

“…This method ablates the afferent and efferent renal nerves 13, 20 . After sacrificing the rats, renal tissue NE content was measured to confirm the completeness of RDX 13, 20 . In the present study, the kidney NE content in all rats was almost undetectable (< 3 ng/g tissue), indicating that denervation was complete.…”

“…After decapitation, trunk blood was collected in chilled tubes containing an inhibitor mixture to prevent AngII degradation for AngII measurement, or in chilled tubes containing EDTA for other measurements, as previously described 13, 22, 23 . Immediately after collecting the blood, half of the right kidney was homogenized in cold methanol and processed to measure the AngII content 24, 25 , while the other half of the kidney tissue was cut and fixed in 10% buffered paraformaldehyde or embedded in OCT compound, and remaining tissues was snap-frozen in liquid nitrogen.…”