Abstract
BACKGROUND: Endothelium-dependent dilatation is mediated by 3 principal vasodilators: nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF). To determine the relative contribution of these factors in endothelium-dependent relaxation, we have generated mice in which the enzymes required for endothelial NO and PGI2 production, endothelial NO synthase (eNOS) and cyclooxygenase-1 (COX-1), respectively, have been disrupted (eNOS-/- and COX-1-/- mice).
METHODS AND RESULTS: In female mice, the absence of eNOS and COX-1 had no effect on mean arterial blood pressure (BP), whereas BP was significantly elevated in eNOS-/-/COX-1-/- males compared with wild-type controls. Additionally, endothelium-dependent relaxation remained intact in the resistance vessels of female mice and was associated with vascular smooth muscle hyperpolarization; however, these responses were profoundly suppressed in arteries of male eNOS-/-/COX-1-/- animals. Similarly, the endothelium-dependent vasodilator bradykinin produced dose-dependent hypotension in female eNOS-/-/COX-1-/- animals in vivo but had no effect on BP in male mice.
CONCLUSIONS: These studies indicate that EDHF is the predominant endothelium-derived relaxing factor in female mice, whereas NO and PGI2 are the predominant mediators in male mice. Moreover, the gender-specific prevalence of EDHF appears to underlie the protection of female eNOS-/-/COX-1-/- mice against hypertension.
Original language | English |
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Pages (from-to) | 796-803 |
Number of pages | 8 |
Journal | Circulation |
Volume | 111 |
Issue number | 6 |
DOIs | |
Publication status | Published - 15 Feb 2005 |
Keywords
- 6-Ketoprostaglandin F1 alpha
- Acetylcholine
- Animals
- Aorta
- Blood Pressure
- Bradykinin
- Capillary Resistance
- Cyclooxygenase 1
- Dose-Response Relationship, Drug
- Electrophysiology
- Endothelium, Vascular
- Endothelium-Dependent Relaxing Factors
- Female
- Genotype
- Male
- Membrane Proteins
- Mesenteric Arteries
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Nitric Oxide Synthase
- Nitric Oxide Synthase Type II
- Nitric Oxide Synthase Type III
- Prostaglandin-Endoperoxide Synthases
- Vascular Resistance
- Vasodilation