Aim: 

Elevated dietary salt intake increases renal medullary COX-2 and PGE₂-synthase activity and cGMP excretion. It was hypothesized that COX-2 activity attenuates blood pressure by stimulation of NO synthesis by eNOS in systemic vasculature and kidney medulla during a high NaCl intake.

Methods: 

COX-2-/- and +/+ mice were given a diet with 0.004% (LS) or 4% (HS) NaCl for 18 days during continuous blood pressure recordings by indwelling catheters. Food, water intake and diuresis were determined in metabolic cages. Urine osmolality and electrolyte excretion were determined. Organs and blood were removed for mRNA/protein analysis and measurement of plasma renin concentration.

Results: 

Food intake was not significantly different between groups whereas water intake, diuresis and Na⁺ excretion was significantly elevated with high salt diet. Plasma renin concentration was elevated by LS compared to HS in both strains but the increase was attenuated in COX-2-/- vs COX-2+/+. There was a significant dependence of blood pressure on salt intake and genotype: COX-2-/- exhibited higher blood pressure than COX-2+/+, particularly at night, both on HS and LS intake, and the largest blood pressure increase observed was at HS in COX-2-/- at night (107.2±0.6 mmHg (day) vs. 117.6±1.0 mmHg (night)). Also COX-2+/+ littermates displayed an increase in blood pressure on HS vs. LS (93.5±0.9 mmHg (LS) vs. 104.4±1.2 mmHg (HS)). There was no change in eNOS mRNA level in kidney medulla by salt intake in either COX genotype.

Conclusion: 

C57BL/6J exhibit salt intake-dependent blood pressure. During LS, COX-2 stimulates renin secretion. COX-2 activity attenuates circadian blood pressure variation during high salt intake.