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 rats. One hour following surgery, 3 x 15-min renal clearances were collected and endothelin (ET)-1 was infused iv at 110 ng/kg/min for 30 min during which time an additional two clearances were 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 Pb2+. By contrast, Pb2+ 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 Ca2+ + Pb2+ (4.8 nmoles/min) were infused for another 105 min; in these experiments, there was no Pb(2+)-induced inhibition of the MAP response to endothelin; the GFR response to the peptide remained blocked. NiCl2 reduced the ET-induced increase in MAP only at 24 nmoles/min; at 4.8 and 24 nmoles/min, nickel attenuated the decrease in GFR induced by ET. Finally, Ca2+ infusion had no effect on the inhibition by Ni2+ of the GFR response to ET. These data illustrate that (i) lead inhibits the cardiorenal actions of endothelin; (ii) a Ca(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 norepinephrine-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.
Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Ohio 45267-0576.
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Banks
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology; D016232:Endothelins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D007854:Lead / Q000494:pharmacology*; D009532:Nickel / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine
D016232:Endothelins; D009942:Organometallic Compounds; D000804:Angiotensin II; D007854:Lead; C022838:nickel chloride; D009532:Nickel; D012964:Sodium; C008261:lead acetate; D002118:Calcium; D009638:Norepinephrine