Interleukin-Driven Inflammation in L-NAME-Induced Hypertension: Comparative Effects of β -Blockers on Endothelial Function
DOI:
https://doi.org/10.52340/GBMN.2025.01.01.142Keywords:
β-blockers, carvedilol, hypertension, interleukins, nebivolol, Nω-nitro-L-arginine methyl ester (L-NAME)Abstract
Background: Hypertension is a multifactorial disorder involving endothelial dysfunction, oxidative stress, and chronic low-grade inflammation. Interleukin (IL)- mediated pathways play a crucial role in the pathogenesis of vascular inflammation, while nitric oxide (NO) deficiency and oxidative imbalance further sustain elevated arterial pressure. Beta-adrenergic blockers (β-blockers) are effective antihypertensive agents; however, their anti-inflammatory and antioxidant effects vary with their pharmacodynamic profiles. Objectives: The study aims to assess the role of interleukin-mediated inflammation in hypertension induced by nitric oxide synthase (NOS) inhibition, and to compare the antihypertensive, antioxidant, and anti-inflammatory effects of different β-blockers (propranolol, metoprolol, carvedilol, nebivolol). Methods: In 86 male rats, hypertension was induced by intraperitoneal administration of L-NAME (40 mg/kg). After 4 weeks of L-NAME treatment, animals received one of four β-blockers (Nebivolol 0.5 mg/kg, propranolol 0.1 mg/kg, metoprolol 3 mg/kg, or carvedilol 2 mg/kg) for the subsequent 4 weeks. Systolic and diastolic arterial pressure (SAP, DAP) were measured non-invasively. ELISA was used to determine serum interleukin levels (IL-6, IL-17, TNF-α). Results: Chronic L-NAME administration resulted in progressive hypertension accompanied by a significant increase in IL-6, IL-17, and TNF-α. β-blocker treatment attenuated these changes to varying extents. Propranolol and metoprolol produced only modest reductions in blood pressure and cytokine levels. Carvedilol significantly lowered IL-6, IL-17, and TNF-α. Nebivolol exerted the most potent effect: arterial pressure returned to near control levels, and cytokine levels (IL-6, IL-17, TNF-α) approached control levels. Conclusions: The interplay between interleukin-mediated inflammation and chronic NOS inhibition maintains hypertension. β-blockers with vasodilatory and antioxidant properties (particularly nebivolol and carvedilol) restore endothelial function more effectively and suppress inflammation more than classical β- blockers. Targeting the oxidative–inflammatory axis may improve outcomes in hypertension associated with inflammation.References
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