We used cyclooxygenase-1 (COX-1)-deficient mice to test the hypothesis that COX-1 regulates blood pressure (BP) and renal hemodynamics. The awake time (AT) mean arterial pressures (MAPs) measured by telemetry were not different between COX-1(+/+) and COX-1(-/-) (131+/-2 versus 126+/-3 mm Hg; NS). However, COX-1(-/-) had higher sleep time (ST) MAP (93+/-1 versus 97+/-2 mm Hg; P<0.05) and sleep-to-awake BP ratio (+8.6%; P<0.05). Under anesthesia with moderate sodium loading, COX-1(-/-) had higher MAP (109+/-5 versus 124+/-4 mm Hg; P<0.05), renal vascular resistance (23.5+/-1.6 versus 30.7+/-1.7 mm Hg . mL(-1) . min(-1) . g(-1); P<0.05) and filtration fraction (33.7+/-2.1 versus 40.2+/-2.0%; P<0.05). COX-1(-/-) had a 89% reduction (P<0.0001) in the excretion of TxB2, a 76% reduction (P<0.01) in PGE2, a 40% reduction (P<0.0002) in 6-ketoPGF1alpha (6keto), a 27% reduction (P<0.02) in 11-betaPGF2alpha (11beta), a 35% reduction (P<0.01) in nitrate plus nitrite (NOx), and a 52% increase in metanephrine (P<0.02). The excretion of normetanephrine, a marker for sympathetic nervous activity, was reduced during ST in COX-1(+/+) (6.9+/-0.9 versus 3.2+/-0.6 g . g(-1) creatinine . 10(-3); P<0.01). This was blunted in COX-1(-/-) (5.1+/-0.9 versus 4.9+/-0.7 g . g(-1) creatinine . 10(-3); NS). Urine collection during ST showed lower excretion of 6keto, 11beta, NOx, aldosterone, sodium, and potassium than during AT in both COX-1(+/+) and COX-1(-/-), and there were positive correlations among these parameters (6keto versus NOx; P<0.005; 11beta versus NOx; P<0.005; and NOx versus sodium; P<0.005). In conclusion, COX-1 mediates a suppressed sympathetic nervous activity and enhanced NO, which may contribute to renal vasodilatation and a reduced MAP while asleep or under anesthesia. COX-1 contributes to the normal nocturnal BP dipping phenomenon.