Gentamicin blockade of slow Ca++ channels in atrial myocardium of guinea pigs.

Are the cardiovascular effects of gentamicin similar to those of calcium antagonists?

“…The present results are thus consistent with those of previous in vestigators, i.e., hypotension (due to vasodi latation) (8-10, 20), reduction of vascular resistance (10), relaxation of vascular smooth muscle (21,22), reduction of the force of contraction of cardiac muscle (10,11,20,23,24) and bradycardia (20). The present experiments further disclosed that GM impairs AV nodal conduction.…”

“…greatly differ between non-dihydropyridine and dihydro pyridine Ca-antagonists, and the binding is also influenced by membrane potentials (2 5). Unlike Ca-antagonists, aminoglycosides are thought to impair the Cat+-influx by competing with Ca2+ for Cat+-binding sites presumably located at the outer orifice of Ca channels (13,14) or displacing Ca 21 from the superficial layer of the plasma membrane in such a way as to reduce available Ca2+ for the transmembrane influx (23,24). Thus, it can be expected that aminoglycosides far less discriminate between cardiac and vascular smooth muscle than Ca-antagonists.…”

Calcium is a competitive inhibitor of gentamicin-renal membrane binding interactions and dietary calcium supplementation protects against gentamicin nephrotoxicity.

“…Gentamicin also inhibits mitochondrial Ca"+ uptake (23). Gentamicin interferes with the slow calcium channels of the sarcolemma in the atrial myocardium of guinea pigs (16). Gentamicin inhibits the glucose transporter of isolated BBM vesicles in vitro and this inhibition is prevented by magnesium (19).…”

“…In this regard, multiple binding sites for the aminoglycoside antibiotics have been characterized in a variety of membranes (9)(10)(11)(12)(13). For developing toxicity, the high affinity site is most critical and has been recently identified as the acidic phospholipids ofthe membrane (9,10 (14), bacterial membranes (15), plasma membranes (16)(17)(18)(19)(20), and subcellular membranes (21)(22)(23) …”

Reduction of experimental gentamicin nephrotoxicity in rats by dietary calcium loading

“…Furthermore, calcium in nutrient medium decreases in vitro gentamicin antibacterial activity (9) and is also reported to reverse or prevent an aminoglycoside-mediated neuromuscular blockade (16). Conversely, gentamicin inhibits transcellular fluxes of calcium in guinea pig atrial muscles (1).…”