EFFECTS OF COBALT OR NICKEL ON THE SYMPATHETICALLY MEDIATED CONTRACTILE RESPONSES IN RAT-ISOLATED VAS-DEFERENS

Subchronic (30 days) exposure of rats to Co(NO3)(2) or NiSO4 (20 mg.kg (-1)) in drinking water caused suppression of the isolated vas deferen s contractile responses to exogenous adeno sine 5'-triphosphate (ATP), noradrenaline, and l-phenylephrine, shifting the concentration-respon se curves to the relevant agonist to the right. Both metals facilitate d the alpha(1)-adrenoceptor antagonistic effects of prazosin, which re sulted in increased pA(2) values for the drug (9.68 +/- 0.13 in contro ls vs. 10.15 +/- 0.12 in Co2+-treated preparations and 12.60 +/- 0.67 in Ni2+-treated preparations). The inhibitory effect of clonidine on t he contractions in response to low-frequency electrical field stimulat ion (EFS) in metal-treated preparations was decreased with pD(2) value s: 10.52 +/- 0.04 in controls, 9.56 +/- 0.13 in Co2+-treated preparati ons and 9.92 +/- 0.16 in Ni2+-treated preparations. The monophasic con tractile responses to low-frequency EFS (0.1 Hz, 1 ms, 80 V) as well a s the first phase of the biphasic contractions after high-frequency lo nglasting EFS (300 pulses, 0.1 ms, 40 V) at 4, 8 or 20 Hz) were signif icantly increased in both groups of heavy metal-treated preparations. Therefore, subchronic exposure to Co2+ or Ni2+ leads to changes in pre - and postjunctional mechanisms underlying the sympathetically mediate d contractile activity of isolated rat vas deferens.