Characteristics of 24 h Telemetered Blood Pressure in eNOS‐Knockout and C57Bl/6J Control Mice

Abstract

The purpose of the present study was to characterize in detail the 24 h blood pressure (BP) phenotype of mice lacking the gene for endothelial nitric oxide synthase (eNOS_/_) and the corresponding control strain (C57Bl/6J). Twenty-four hour BP recordings were made in conscious 12-to 16-week-old male mice 10 days following the implantation of a BP telemeter (n = 9 per group). The BP and heart rate of both strains were markedly affected by brief locomotor activity cycles, resulting in bimodal distributions of BP and heart rate within both light and dark periods. Data from active periods were associated with the higher of the two modes, whereas data from inactive periods were associated with the lower of the two modes. In eNOS_/_ mice, the 24 h average BP level was significantly elevated (+15 %, 104 ± 2 vs. 119 ± 1 mmHg), as was its daily range (+44 %), its coefficient of variation (+26 %), dark-light difference (+48 %), and the separation of the two modes of its distribution (+41 %). Pulse pressure was also significantly greater (+23 %) in eNOS_/_ mice. The 24 h heart rate level did not differ between control and eNOS_/_ mice. Considerable variation was noted among previously published values of BP in eNOS_/_ mice, but not in the corresponding control mice. Our results indicate that eNOS_/_ mice have mild hypertension that is accompanied by more pronounced increases in BP lability and/or reactivity. Our results also demonstrate a marked effect of locomotor activity on BP in mice, which may confound short-term measurements of BP.

Nitric Oxide Synthase Inhibition Induces Renal Medullary Hypoxia in Conscious Rats

“…This suggests that NO causes diurnal fluctuations in medullary oxygenation. NO is involved in the regulation of circadian rhythmicity in blood pressure 28, 29, 30. A shift in peak blood pressure of 4 hours was found in the current study.…”

“…Healthy renal pO 2 in cortex and medulla shows circadian rhythmicity 27. NO depletion is known to affect the diurnal rhythm of blood pressure in rodents,28, 29, 30 but effects on renal oxygenation circadian rhythm are as yet unknown.…”

Nephron‐Specific Disruption of Nitric Oxide Synthase 3 Causes Hypertension and Impaired Salt Excretion

“…The salt‐sensitive BP finding is supported by previous studies wherein global NOS3 KO caused hypertension,16, 17 but re‐expressing vascular endothelial NOS3 in the setting of global NOS3 KO did not normalize BP18 suggesting that non‐endothelial NOS3 modulates BP. Importantly, the hypertension and impaired Na + excretion in NOS3 KO mice was not associated with altered GFR.…”

Association of eNOS Glu298Asp gene polymorphism with circadian blood pressure rhythm

“…1 These results are supported by several studies which have shown a disturbance in circadian rhythms in genetically modified mice (eNOS-knockout mice). 7 The results of our study agree with this work and support the role of eNOS in circadian BP regulation in humans.…”