EFFECTS OF 2-NICOTINAMIDOETHYL NITRATE ON AGONIST-SENSITIVE CA++ RELEASE AND CA++ ENTRY IN RABBIT AORTA

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 233  (1) , 100-111
Abstract
The effects of 2-nicotinamidoethyl nitrate (SG-75) on norepinephrine (NE)- and KCl-induced responses in rabbit aorta were quantitated, correlated with 45Ca studies and compared with the effects of nifedipine (NIF) on similar parameters. NE- and KCl-induced dose-response relationships were differentially depressed by SG-75 (NE .mchgt. KCl) and NIF (KCl .mchgt. NE). Responses to KCl were relatively insensitive to prior SG-75, yet moderately relaxed by subsequent SG-75. NIF markedly inhibited and completely relaxed similar responses. Responses to NE were relaxed and inhibited with SG-75, but unaffected by NIF. Responses to NE in La3+ or 0-Ca2+ + ethylene glycol bis(.beta.-aminoethyl ether)N,N''-tetraacetic acid plus D600 (with and without KCl) solutions were phasic, reduced by SG-75 and 0-Ca2+ + ethylene glycol bis(.beta.-aminoethyl ether)N,N''-tetraacetic acid plus D600 solution (with and without KCl) were attenuated by SG-75. Equilibrated (60 min) La3+-resistant (residual), high apparent affinity Ca2+ binding was increased 26% with SG-75 and decreased 34% with NIF, yet neither altered the rate of exchange (10 min). Rate of exchange at low apparent affinity, residual sites was increased 21% by SG-75 without altering equilibrated values, whereas NIF reduced equilibrated values 11%, without affecting rate. NE reduced, SG-75 + NE augmented and NIF + NE decreased, in an additive fashion, high apparent affinity, residual bound Ca2+. Residual Ca2+ binding at low apparent affinity sites was increased with 160 mM substituted KCl (380%). This increase was only partially inhibited with SG-75, and eliminated by NIF. Net Ca2+ efflux was persistently slowed by SG-75 and unaltered by NIF. The primary effects of SG-75 appear to be depression of Ca2+ release and inhibition of receptor-operated (potential-independent) Ca2+ entry, with limited attenuation of voltage-dependent Ca2+ entry. NIF primarily inhibits voltage-dependent Ca2+ entry.