Publication | Open Access
Role of endothelium-derived nitric oxide in the regulation of blood pressure.
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References
1989
Year
HypertensionCardiovascular DiseaseNitric OxideMedicinePhysiologyVascular PharmacologyEndothelial DysfunctionEndothelium-derived Nitric OxideVascular BiologyAnesthesiologyPharmacotherapyAnesthesiaPharmacologyNitric Oxide FormationNitrosative StressBlood PressureNeuromuscular BlockadeOxidative Stress
The study examined how endothelium‑derived nitric oxide regulates blood pressure in anesthetized rabbits by inhibiting its synthesis with L‑N‑MMA. L‑N‑MMA, a selective inhibitor of NO formation from L‑arginine, was administered (3–100 mg kg⁻¹) and its effects on arterial pressure and acetylcholine‑induced hypotension were measured, with L‑arginine used to reverse the inhibition. L‑N‑MMA produced a dose‑dependent, long‑lasting rise in mean arterial pressure, blocked acetylcholine‑induced hypotension but not glyceryl trinitrate, and its effects were reversed by L‑arginine, confirming that endothelial NO derived from L‑arginine regulates blood pressure and acetylcholine’s hypotensive action.
The role of endothelium-derived nitric oxide in the regulation of blood pressure in the anesthetized rabbit was studied with N omega-monomethyl-L-arginine (L-NMMA), a specific inhibitor of its formation from L-arginine. L-NMMA (3-100 mg.kg-1), but not its D-enantiomer, induced a dose-dependent long-lasting (15-90 min) increase in mean systemic arterial blood pressure. L-NMMA (100 mg.kg-1) also inhibited significantly the hypotensive action of acetylcholine, without affecting that of glyceryl trinitrate. Both these actions of L-NMMA were reversed by L-arginine (300 mg.kg-1), but not by D-arginine (300 mg.kg-1), indomethacin (1 mg.kg-1), prazosin (0.3 mg.kg-1), or by vagotomy. The effects of L-NMMA in vivo were associated with a significant inhibition of the release of nitric oxide from perfused aortic segments ex vivo. This inhibition was reversed by infusing L-arginine through the aortic segments. These results indicate that nitric oxide formation from L-arginine by the vascular endothelium plays a role in the regulation of blood pressure and in the hypotensive actions of acetylcholine.
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