Parallel regulation of constitutive NO synthase and renin at JGA of rat kidney under various stimuli

Abstract

Four chronic experiments were performed to assess changes in the activity and gene expression of type I nitric oxide synthase (NOS) at the macula densa (MD) and of renin expression and immunoreactivity (IR) at the juxtaglomerular apparatus (JGA) of rat kidney, as follows: 1) two-kidney, one-clip Goldblatt hypertension (2K1C, for 3 and 40 days; sham operation for controls), 2) furosemide treatment (150 mg/kg-1.day-1 ip for 5 days), 3) chronic low-salt diet (0.02%) vs. high-salt diet (3%; both for 11 days), and 4) chronic blockade of NOS by nitro-L-arginine methyl ester (L-NAME, 40 mg.kg-1.day-1 for 2 mo). NOS and renin gene expression, NOS enzyme activity and renin IR were semiquantitatively evaluated with histochemical methods (NADPH diaphorase, in situ hybridization, immunohistochemistry). In 2K1C, marked increases were induced in NOS and renin in the ischemic vs. contralateral kidneys both after 3 and 40 days, respectively (P < 0.05). Related to controls, significant increases in the ischemic kidney were encountered after 3 and 40 days, whereas contralateral suppression of NOS and renin was found only after 40 days. Furosemide treatment resulted in a marked increase of both NOS and renin levels compared with controls (P < 0.05). Salt restriction induced a significant elevation of NOS levels compared with salt loading (P < 0.05), whereas only minor changes were evident in renin levels. L-NAME treatment resulted in a moderate reduction of NOS activity (not significant), whereas renin levels were markedly reduced (P < 0.05). These results show that NOS activity and gene expression are inversely related to chronic changes in renal perfusion, salt balance, and salt transport at the distal tubule in parallel with the known response of renin to these changes. Inhibition of NOS decreases renin levels at the JGA. The histochemical findings support previous concepts that MD-derived NO is involved in the control of renin synthesis.

Changes of Cell Volume and Nitric Oxide Concentration in Macula Densa Cells Caused by Changes in Luminal NaCl Concentration

“…Results regarding the distal [NaCl] and the production of NO in MD in earlier studies are somewhat conflicting. In studies concerning the influence of sodium intake on NOS expression, it has been found that sodium deficiency stimulates nNOS expression, as do other conditions that are likely to result in reduced MD [NaCl] or transport, such as furosemide administration and unilateral stenosis of the renal artery (31,32). In contrast, high-salt diets and hyperfusion significantly inhibited nNOS mRNA expression (31,32).…”

“…In studies concerning the influence of sodium intake on NOS expression, it has been found that sodium deficiency stimulates nNOS expression, as do other conditions that are likely to result in reduced MD [NaCl] or transport, such as furosemide administration and unilateral stenosis of the renal artery (31,32). In contrast, high-salt diets and hyperfusion significantly inhibited nNOS mRNA expression (31,32). But in the other experiments in which the urinary excretions of nitrate and nitrite were measured, Shultz and Tolins (33) found that high salt intake generated more NO in MD cells.…”

Augmented Renal Vascular nNOS and Renin Protein Expression in Angiotensin Type 1 Receptor Null Mice

“…In terms of the regulation of nNOS and renin by multiple stimuli, again there are many circumstances in which nNOS and renin protein expression are coordinately regulated. Bosse et al (1995) have shown parallel changes in renal nNOS and renin expression in the following models: two-kidney, one-clip Goldblatt hypertensive rats, chronic low-salt diet, chronic furosemide treatment, and inhibition of NOS with L-NAME. These parallel changes in NOS and renin suggest an involvement of NO formation in the regulation of renin or vice versa.…”

Diabetic Endothelin B Receptor–Deficient Rats Develop Severe Hypertension and Progressive Renal Failure

“…The changes correspond to the levels of renal renin synthesis and to plasma renin levels under various conditions (24). The amount of renin mRNA and immunoreactive renin-containing arterioles are known to be largely co-localized and to vary in parallel (25). Quantification of nNOS was performed similarly, as described previously (25).…”

“…The amount of renin mRNA and immunoreactive renin-containing arterioles are known to be largely co-localized and to vary in parallel (25). Quantification of nNOS was performed similarly, as described previously (25).…”