Staehr, Mette3; Hansen, Pernille B L3; Madsen, Kirsten3; Vanhoutte, Paul M3; Nüsing, Rolf Michael2; Jensen, Boye L3
1 Kardiovaskulær og Renal Forskning, Department of Molecular Medicine, Det Sundhedsvidenskabelige Fakultet, SDU2 unknown3 Kardiovaskulær og Renal Forskning, Department of Molecular Medicine, Det Sundhedsvidenskabelige Fakultet, SDU
Experiments were designed to test the hypothesis that COX-2 activity attenuates the blood pressure increase during high NaCl intake by stimulation of eNOS-mediated NO synthesis in the kidney medulla. COX-2(-/-) (C57BL6) and (+/+) mice were fed a diet with 0.004% (LS) or 4% (HS) NaCl for 18 days. Arterial blood pressure was recorded continuously using indwelling catheters. Food and water intake and diuresis were measured in metabolic cages. Urine osmolality and excretion of electrolytes, cGMP, cAMP and NOx were determined, as well as plasma NOx and cGMP. There was a significant dependence of blood pressure on salt intake and genotype: COX-2(-/-) exhibited higher blood pressure than COX-2(+/+) both on HS and LS intake. COX-2(+/+) littermates displayed an increase in blood pressure on HS vs. LS (102.3±1.1 mmHg vs. 91.9±0.9 mmHg) day and night. The mice exhibited significant blood pressure increases during the awake phase (night) that were larger in COX-2(-/-) on HS diet compared to COX-2(+/+). Water intake, diuresis, Na(+) and osmolyte excretions and NOx and cGMP excretions were significantly and similarly elevated with HS in COX-2(-/-) and COX-2(+/+). In summary, C57BL6 mice exhibit a salt intake-dependent increase in arterial blood pressure with increased renal NO production. COX-2 activity has a general lowering effect on arterial blood pressure. COX-2 dampens NaCl-induced, increases in arterial blood pressure in the awake phase. In conclusion, COX-2 activity attenuates the changes in nocturnal blood pressure during high salt intake and COX-2 activity is not necessary for increased renal NO formation during elevated NaCl intake.
American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 2013, Vol 304, Issue 10