Effects of long-term inhibition of neuronal nitric oxide synthase on blood pressure and renin release.

Abstract

Nitric oxide (NO) produced by neuronal NO-synthase (nNOS) in macula densa cells may be involved in the control of renin release. 7-Nitro indazole (7-NI) inhibits nNOS, and we investigated the effect of short- (4 days) and long-term (4 weeks) 7-NI treatment on blood pressure (BP), plasma renin concentration (PRC) and glomerular filtration rate (GFR) in rats on different salt diets. Rats were divided into three groups and given low-salt (LS), normal (C) and high-salt (HS) diets. Each diet group was subdivided into two groups treated either with 7-NI or vehicle. Long-term 7-NI-treated rats (LS and C) showed increased BP compared with controls (LS: 149 +/- 4 vs. 133 +/- 3; C: 146 +/- 4 vs. 127 +/- 4 mmHg). Blood pressure in HS rats did not differ from that in controls. Plasma renin concentration was stimulated in LS-rats (251 +/- 64 mGU mL(-1)) compared with C and HS rats (42 +/- 8 and 39 +/- 5 mGU mL(-1), respectively) but was not significantly affected by chronic 7-NI treatment (350 +/- 103, 49 +/- 10 and 50 +/- 15 mGU mL(-1) in LS, C and HS, respectively). In rats treated with 7-NI for 4 days, no effect on BP was seen, but PRC was increased in 7-NI treated LS rats compared with vehicle treated LS rats (107 +/- 15 vs. 56 +/- 1 mGU mL(-1)). Stimulation of PRC in LS rats was further enhanced by 7-NI after 4 days of treatment, but not affected in rats treated for 4 weeks. This suggests that inhibition of nNOS stimulates renin release but that this stimulatory effect in the long run might be depressed by the increase in blood pressure.