Direct Blood Pressure Monitoring in Laboratory Rodents via Implantable Radio Telemetry

Soluble epoxide hydrolase (sEH) is inhibited by electrophilic lipids by their adduction to Cys521 proximal to its catalytic center. This inhibition prevents hydrolysis of the enzymes' epoxyeicosatrienoic acid (EET) substrates, so they accumulate inducing vasodilation to lower blood pressure (BP). We generated a Cys521Ser sEH redoxdead knockin (KI) mouse model that was resistant to this mode of inhibition. The electrophilic lipid 10-nitro-oleic acid (NO 2 -OA) inhibited hydrolase activity and also lowered BP in an angiotensin II-induced hypertension model in wild-type (WT) but not KI mice. Furthermore, EET/dihydroxy-epoxyeicosatrienoic acid isomer ratios were elevated in plasma from WT but not KI mice following NO 2 -OA treatment, consistent with the redox-dead mutant being resistant to inhibition by lipid electrophiles. sEH was inhibited in WT mice fed linoleic acid and nitrite, key constituents of the Mediterranean diet that elevates electrophilic nitro fatty acid levels, whereas KIs were unaffected. These observations reveal that lipid electrophiles such as NO 2 -OA mediate antihypertensive signaling actions by inhibiting sEH and suggest a mechanism accounting for protection from hypertension afforded by the Mediterranean diet.thiol | cardiovascular

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“…BP was assessed by remote radiotelemetry in conscious freely moving mice as described previously (48)(49)(50).…”

Section: Methodsmentioning

confidence: 99%

Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase

Charles

Rudyk

Prysyazhna

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…20 Examination of 24-hour telemetry data revealed a significant increase in systolic blood pressure (SBP) over time in both male and female CNP ecKO mice, as compared with their controls (Figure 2A through 2D). In both males and females, Figure S2A and S2B).…”

Section: High Blood Pressure In Cnp Ecko Micementioning

confidence: 97%

Endothelium-Derived C-Type Natriuretic Peptide Contributes to Blood Pressure Regulation by Maintaining Endothelial Integrity

et al. 2017

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We previously reported the secretion of C-type natriuretic peptide (CNP) from vascular endothelial cells and proposed the existence of a vascular natriuretic peptide system composed of endothelial CNP and smooth muscle guanylyl cyclase-B (GC-B), the CNP receptor, and involved in the regulation of vascular tone, remodeling, and regeneration. In this study, we assessed the functional significance of this system in the regulation of blood pressure in vivo using vascular endothelial cell–specific CNP knockout and vascular smooth muscle cell–specific GC-B knockout mice. These mice showed neither the skeletal abnormality nor the early mortality observed in systemic CNP or GC-B knockout mice. Endothelial cell–specific CNP knockout mice exhibited significantly increased blood pressures and an enhanced acute hypertensive response to nitric oxide synthetase inhibition. Acetylcholine-induced, endothelium-dependent vasorelaxation was impaired in rings of mesenteric artery isolated from endothelial cell–specific CNP knockout mice. In addition, endothelin-1 gene expression was enhanced in pulmonary vascular endothelial cells from endothelial cell–specific CNP knockout mice, which also showed significantly higher plasma endothelin-1 concentrations and a greater reduction in blood pressure in response to an endothelin receptor antagonist than their control littermates. By contrast, vascular smooth muscle cell–specific GC-B knockout mice exhibited blood pressures similar to control mice, and acetylcholine-induced vasorelaxation was preserved in their isolated mesenteric arteries. Nonetheless, CNP-induced acute vasorelaxation was nearly completely abolished in mesenteric arteries from vascular smooth muscle cell–specific GC-B knockout mice. These results demonstrate that endothelium-derived CNP contributes to the chronic regulation of vascular tone and systemic blood pressure by maintaining endothelial function independently of vascular smooth muscle GC-B.

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“…For a review of the progress in radiotelemetry in small animals, please refer to Kramer et al (2001). Similarly, the interested reader can consult the original publication by Mills et al (2000) describing the characteristics of the mouse transmitters from DSI as well as the review article by Huetteman & Bogie (2009) that describes in details the surgical procedures to implant DSI transmitters in rats and mice. Because of the surgery needed for the installation of the transmitters, radiotelemetry can be considered an invasive technique.…”

Section: Direct Non-invasive Method: Radiotelemetrymentioning

confidence: 99%

Radio-Telemetry in Biomedical Research - Radio-Telemetry Blood Pressure Measurements in Animal Models of Hypertension, How It Revolutionized Hypertension Research

Dumas¹,

Chiche²,

Tremblay³

et al. 2011

Modern Telemetry

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Direct Blood Pressure Monitoring in Laboratory Rodents via Implantable Radio Telemetry

Cited by 52 publications

References 30 publications

Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase

Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase

Endothelium-Derived C-Type Natriuretic Peptide Contributes to Blood Pressure Regulation by Maintaining Endothelial Integrity

Radio-Telemetry in Biomedical Research - Radio-Telemetry Blood Pressure Measurements in Animal Models of Hypertension, How It Revolutionized Hypertension Research

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