The polycationic aminoglycosides modulate the vasoconstrictive effects of endothelin: relevance to cerebral vasospasm

British Journal of Pharmacology
G WickmanB Vollrath

Abstract

1. The vasoactive peptide endothelin (ET) has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid haemorrhage. In these studies we investigated the involvement of protein kinase C (PKC) in sustained vasoconstriction induced by ET-1 in canine cerebral arteries. We also examined the ability of the aminoglycoside antibiotics to reverse the effects mediated by ET-1 in canine cerebrovascular smooth muscle cells (CVSMC). 2. The ET(A) receptor antagonist, BQ-123, showed a competitive inhibition of the ET-1 responses. 3. The vasoconstrictor action of both ET-1 (0.5 nM) and phorbol myristate acetate (PMA) (160 nM) was reversed by a selective PKC inhibitor, Ro-32-0432. 4. In cerebral arteries precontracted with ET-1 the aminoglycosides caused a concentration-dependent relaxation. The EC(50s) for the relaxation were as follows: 0.54+/-0.05, 0.63+/-0.01, 1.88+/-0.46 and 2.3+/-0.92 mM for gentamicin, neomycin, streptomycin and kanamycin, respectively. 5. Gentamicin caused a concentration-dependent decrease of the PMA-induced responses in calcium free medium. 6. PKC activity was elevated in CVSMC exposed to ET-1 (170%) and PMA (167%) for a period of time (60 min) corresponding to maximum tonic contraction induced...Continue Reading

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Citations

Sep 24, 2010·Kidney International·Jose M Lopez-NovoaFrancisco J Lopez-Hernandez
Jul 3, 2007·Toxicology and Applied Pharmacology·Carlos Martínez-SalgadoJosé M López-Novoa
Jan 29, 2005·British Journal of Pharmacology·Fatima MraicheBozena Vollrath
Nov 19, 2003·British Journal of Pharmacology·Jun Zhao, Dirk F van Helden
Nov 26, 2002·Neurosurgery·Michael ChowNeal F Kassell
Jul 6, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Megan M VucovichJeff Reese
Apr 20, 2016·The Cochrane Database of Systematic Reviews·Arturo J Martí-CarvajalDaniel Simancas-Racines
Aug 31, 2021·Current Reviews in Clinical and Experimental Pharmacology·Ufuk Cakir, Cuneyt Tayman

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