Lead and nickel alter the cardiorenal actions of endothelin in the rat

In the current study, we have determined to what extent lead and nickel alter the cardiorenal actions of endothelin in pentobarbital anesthetized female rates. One hour following surgery, 3 x 15-min renal clearances were collected and endothelin (ET)-1 was infused iv at 100 ng/kg/min for 30 min during which time an additional two clearances was collected. Lead (infused as lead acetate throughout the experiment) at 4.8 nmoles/min and 24 nmoles/min significantly attenuated the ET-induced increase in mean arterial pressure (MAP); lead infused at 0.48 nmoles/min had no effect. An ET-induced decrease in the glomerular filtration rate (GFR) in control rats was completely blocked by the higher doses of Pb{sup 2+}. By contrast, Pb{sup 2+} had no effect on angiotensin II or norepinephrine induced increases in MAP. In additional experiments, calcium chloride was infused at 500 nmoles/min for 105 min, then Ca{sup 2+} + Pb{sup 2+} (4.8 nmoles/min) were infused for another 105 min; in these experiments, there was no Pb{sup 2+}-induced inhibition of the MAP response to endothelin: the GFR response to the peptide remained blocked. NiCl{sub 2} reduced the ET-induced increase in MAP only at 24 nmoles/min; at 4.8 and 24 nmoles/min, nickel attentuated the decrease in GFR inducedmore » by ET. Finally, Ca{sup 2+} infusion had no effect on the inhibition by Ni{sup 2+} of the GFR response to ET. These data illustrate that (i) lead inhibits the cardiorenal actions of endothelin; (ii) a Ca{sup 2+}-related process is involved the systemic but not the renal component of this inhibition; (iii) since the heavy metal does not affect angiotensin II or nonrepinephrine-induced increases in MAP, the inhibition by lead of the systemic response is relatively specific for endothelin; and (iv) nickel also inhibits the renal response to the peptide but higher doses are required to inhibit the systemic response. 35 refs., 4 figs., 2 tabs.« less