Sustained hypertension despite endothelial-specific eNOS rescue in eNOS-deficient mice

Area of Science:

• Cardiovascular Physiology
• Molecular Biology
• Hypertension Research

Background:

• Endothelial nitric oxide synthase (eNOS) plays a crucial role in regulating vascular tone and blood pressure.
• The contribution of non-endothelial eNOS to blood pressure homeostasis remains incompletely understood.

Purpose of the Study:

• To investigate the role of non-endothelial eNOS in blood pressure regulation.
• To determine if restoring eNOS expression solely in the vascular endothelium can normalize blood pressure in eNOS-deficient mice.

Main Methods:

• Generation of a double transgenic mouse strain (eNOS-Tg/KO) with endothelial-specific expression of bovine eNOS in eNOS-deficient mice.
• Assessment of eNOS expression in various tissues including aorta, myocardium, kidney, brain stem, and skeletal muscle.
• Evaluation of aortic and systemic blood pressure responses to pharmacological stimuli (acetylcholine, phenylephrine, L-NAME) using organ bath studies and in vivo measurements.

Main Results:

• Complete normalization of aortic reactivity to acetylcholine, phenylephrine, and NO-donors in eNOS-Tg/KO mice.
• Acetylcholine-induced hypotension and L-NAME-induced hypertension were observed in eNOS-Tg/KO and wild-type mice, but not in eNOS-KO mice.
• Despite vascular eNOS reconstitution, mean, systolic, and diastolic blood pressure remained significantly elevated in eNOS-Tg/KO mice, similar to eNOS-KO mice.
• Chronic L-NAME treatment increased blood pressure in wild-type mice but had no effect on hypertensive eNOS-KO and eNOS-Tg/KO mice.

Conclusions:

• Functional reconstitution of eNOS within the vasculature of eNOS-deficient mice did not restore normal blood pressure levels.
• These findings suggest that eNOS activity in non-vascular tissues may play a significant role in physiological blood pressure regulation.