Increased nitric oxide synthase activity despite lack of response to endothelium-dependent vasodilators in postischemic acute renal failure in rats.

Abstract

Lack of response to endothelium-dependent vasodilators generally has been considered to be evidence for decreased nitric oxide synthase (NOS) activity and NO generation after ischemic or hypoxic injury to vital organs including the kidney. In this study, renal blood flow (RBF) responses to endothelium-dependent vasodilators acetylcholine and bradykinin and the endothelium-independent vasodilator prostacyclin, the nonselective NOS inhibitor L-NAME (without and with L-arginine), the inducible NOS inhibitor aminoguanidine, and the NO-donor sodium nitroprusside were examined in 1-wk norepinephrine-induced (NE) and sham-induced acute renal failure (ARF) rats. Compared with sham-ARF, there was no increase in RBF to intrarenal acetylcholine and bradykinin, but a comparable RBF increase to prostacyclin in NE-ARF kidneys. However, there was a signiflcantiy greater decline in RBF to intravenous L-NAME in NE-than sham-ARF rats (-65±8 vs. -37±5%, P < 0.001) which was completely blocked by prior L-arginine infusion. There was no change in RBF to the inducible NOS specific inhibitor aminoguanidine. Unlike sham-ARF, there was no increase in RBF to intrarenal sodium nitroprusside in NE-ARF. Immunohistochemistry and immunofluorescence detection of constitutive (c) NOS using mouse monoclonal antibody were carried out to positively determine the presence of cNOS in NE-ARF. 90% of renal resistance vessels showed evidence of endothelial cNOS in both sham-and NE-ARF. Taken together, results of these experiments are consistent with the conclusion that NOS/NO activity is, in fact, maximal at baseline in 1-wk NE-ARF and cannot be increased further by exogenous stimuli of NOS activity. The increased NOS is likely of the constitutive form and of endothelial origin. It is suggested that the increased NOS activity Clin. Invest. 1995. 96:631-638.)

The subtype 2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats.

“…All types of NOS genes are present in the kidney (16)(17)(18)(19). The effects of Ang II on NOS expression in the kidney to our knowledge have not been studied previously.…”

Protective Effect of Melatonin and 1,25-Dihydroxyvitamin D3 on Renal Ischemia–Reperfusion Injury in Rats

“…It was suggested that NOS activity, probably endothelial constitutive NOS (cNOS), increased in response to ischemia-induced renal vasoconstrictor activity. 41 Ischemic injury itself may increase smooth muscle cytosolic calcium or increase oxygen radical generation, providing potent vasoconstrictor stimulation to which NOS activation is a modulating response. 41 Increased NO levels in I/R injury may be due to increased NOS activity and ROS/RNS production.…”

“…41 Ischemic injury itself may increase smooth muscle cytosolic calcium or increase oxygen radical generation, providing potent vasoconstrictor stimulation to which NOS activation is a modulating response. 41 Increased NO levels in I/R injury may be due to increased NOS activity and ROS/RNS production. It has been shown that VD3 42,43 and melatonin 44,45 inhibit expression of NOS.…”

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

“…In addition to decreased vasodilation proprieties, arterioles can exhibit increased reactivity to vasoconstrictive agents (75). Many vasoconstrictive agents have been suggested to accompany the postischemic increase in vascular tone, including endothelin, angiotensin II (76), thromboxane A 2 (77), leukotriene C 4 (78), adenosine (14), endothelium-derived prostaglandin H2, and sympathetic nerve stimulation (13,18).…”