Journal of Clinical & Experimental Pharmacology

Abstract

Canine Cerebral Artery Vasodilation Caused by Aminoglycoside Antibiotics: The Mechanism

Hari Prasad Sonwani*

In canine cerebral arteries and in cultured cerebrovascular smooth muscle cells activated with Oxyhemoglobin (OxyHb), a blood component linked to the pathophysiology of cerebrovascular spasm, the effects of aminoglycoside antibiotics were investigated. The aminoglycosides reduced isometric tension in cerebral artery rings pre-contracted with OxyHb (10 μM) in a concentration-dependent manner. The relaxation's EC₅₀ values for neomycin, gentamicin, streptomycin, and kanamycin were 0.4 ± 0.1 mM (n=α), 0.53 ± 0.08 mM (n=12), 1.α ± 0.3 mM (n=7), and 3.9 ± 0.5 mM (n=5), respectively. The quantity of positive charges in the molecules is roughly correlated with this potency ranking. Additionally, the contractions to prostaglandin F2a (1 μM) and depolarizing potassium chloride concentrations (α0 mM) were suppressed by the aminoglycosides. The potency was neomycin, gentamicin, streptomycin, and kanamycin in that sequence. The ease of mind persisted in prepared arteries devoid of endothelium. In response to PGF2a, neomycin (5 mM) eliminated the Ca²⁺-independent contraction. When Fura-2 was added to cerebrovascular smooth muscle cells, OxyHb (1 μM) markedly increased the intracellular calcium ((Ca²⁺)i) concentration by 330%. The administration of EC₅₀-corresponding amounts of neomycin, gentamicin, kanamycin, and streptomycin decreased the effects of OxyHb on (Ca²⁺)i by approximately 50%, resulting in values of 221 ± 35 nM (n=7), 270 ± 31 nM (n=7), 229 ± 33 nM (n=α), and 240 ± α nM (n=5). These findings imply that the aminoglycosides' impacts on the OxyHb-induced contraction and the sustained rise in (Ca²⁺)i may stem from a variety of mechanisms, such as PLC inhibition, calcium extrusion mechanism protection, and interference with the (Ca²⁺)i accumulation process.

Published Date: 2025-01-13; Received Date: 2023-11-15